THE BEHAVIORAL AND BRAIN SCIENCES (1981) 4, 459-514

Printed in the United States ot America

Reticulo-cortical activity and behavior: A

critique of the arousal theory and a new
synthesis
C.H. Vanderwolf
Department of Psychology, University of Western Ontario, London,
Ontario, Canada N6A 5C2

T.E. Robinson
Neuroscience Laboratory, University of Michigan, Ann Arbor, Mich. 48109

Abstract: It is traditionally believed that cerebral activation (the presence of low voltage fast electrical activity in the neocortex
and rhythmical slow activity in the hippocampus) is correlated with arousal, while deactivation (the presence of large amplitude
irregular slow waves or spindles in both the neocortex and the hippocampus) is correlated with sleep or coma. However, since
there are many exceptions, these generalizations have only limited validity. Activated patterns occur in normal sleep (active or
paradoxical sleep) and during states of anesthesia and coma. Deactivated patterns occur, at times, during normal waking, or
during behavior in awake animals treated with atropinic drugs. Also, the fact that patterns characteristic of sleep, arousal, and
waking behavior continue in decorticate animals indicates that reticulo-cortical mechanisms are not essential for these aspects of
behavior.
These puzzles have been largely resolved by recent research indicating that there are two different kinds of input from the
reticular activating system to the hippocampus and neocortex. One input is probably cholinergic; it may play a role in stimulus
control of behavior. The second input is noncholinergic and appears to be related to motor activity; movement-related input to
the neocortex may be dependent on a trace amine.
Reticulo-cortical systems are not related to arousal in the traditional sense, but may play a role in the control of adaptive
behavior by influencing the activity of the cerebral cortex, which in turn exerts control over subcortical circuits that co-ordinate
muscle activity to produce behavior.

Keywords: arousal; cerebral cortex; EEG; hippocampus; motor activity; reticular system; sleep

A considerable portion of any comprehensive current
textbook of neuroscience is usually devoted to the
physiological basis of consciousness, attention, sleep,
and arousal. A basic source of data for such discussions
is the presumed relation between brain wave activity
(electroencephalogram, EEG) and behavior. It is
usually stated that the presence of low voltage fast
activity (LVFA) in the neocortex is a correlate of
arousal, alertness, attention, or consciousness, while
spindles and large amplitude slow activity are corre-
lates of drowsiness, sleep, or coma. The definition of
these various states in experimental animals is usually
based on common sense criteria such as waking or
sleeping posture, spontaneous movement, and respon-
siveness to sensory stimuli. According to Rossi and
Zanchetti (1957, p. 386), "The close relationship that
exists between EEG patterns and behavioral manifesta-
tions of wakefulness and sleep appears to justify the
assumption that electrocortical records may be
regarded as a reliable test of behavior, even in those
preparations in which it is impossible to analyze
directly the behavior itself." A figure from Penfield
and Jasper (1954) which illustrates the widely accepted
view that cortical wave activity is related to the level of
consciousness has been reproduced in many textbooks
(Fig. 1). According to some authors, the relation
between internal states of arousal and overt behavior is
complex (Hebb 1955; Malmo 1959). Thus, total behav-
ioral immobility may occur during low arousal (as in
boredom, drowsiness, or stupor) or during high arousal
(as in freezing from terror).
The above ideas originated in investigations carried
out mainly in the years between 1930 and 1960 (see
reviews by Lindsley 1960 and Moruzzi 1972). During
this period it was established that large amplitude slow
wave activity is very prominent in the neocortex
during sleep while LVFA is generally present during
the waking state. The differing characteristics of the
human electroencephalogram (EEG) at various times
during normal sleep led to the recognition of a number
of different stages of sleep (Hess 1964). The observa-
tion that dreaming is frequently associated with LVFA
(see below) led many investigators to assume that three
distinct states of consciousness occur normally. 1)
waking consciousness, 2) dreaming consciousness, both
associated with LVFA, and 3) loss of consciousness,
associated with large slow waves.
The physiological basis of natural sleep-waking

Q1981 Cambridge University Press 0140-525X/81/030459-56/$04.00/0 459

Vanderwolf & Robinson: Reticulo-cortical activity and behavior
EXCITED
RELAXED
DROWSY
ASLEEP
DEEP SLEEP
SOjiV
1 SEC.
Figure. 1. Characteristic electroencephalograms during
variations in states of conciousness. (From Penfield & Jasper
1954, p. 188; reprinted with permission of Little, Brown &
Co.)
phenomena was clarified by a long series of investiga-
tions which indicated that high levels of activity in the
ascending reticular activating system (ARAS) produce
LVFA in the neocortex while low levels of activity in
this system result in slow waves or spindles in the
neocortex. Slow waves or spindles may also occur as a
result of increased activity in an ascending reticulocor-
tical slow wave inducing system which appears to act as
an antagonist to the ARAS (Moruzzi 1972). A widely
accepted interpretation of these findings is that natu-
rally occuring sleep and waking states are dependent
on ascending reticulo-cortical activity.
Although the foregoing ideas originated many years
ago, they remain influential today. In the words of one
recent reviewer (Kandel 1979, p. 540) "Even a rapid
review of the literature of the last 10 years makes it
clear that our understanding of the relation of the
reticular formation to behavioral arousal has not been
significantly advanced" (since the late 1950s). We
believe that this assessment is inaccurate. There is a
wealth of data which shows that the textbook view of
reticulo-cortical activity and behavior described above
(the arousal theory) is wrong in several basic respects.
Further, we shall present an alternative point of view
which appears to provide a satisfactory interpretation
of most of the data in this field.
How well does neocortical slow wave activity
correlate with the level of arousal?
Even a casual examination of neocortical activity in a
normal laboratory animal (usually a rat or cat) indi-
cates that long trains of slow wave activity are very
common during behavioral sleep but LVFA invariably
460 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
r occurs upon awakening, regardless of whether awaken-
ing happens naturally or as a result of stimulation of the
reticular formation. Although these observations
suggest that there is a relation between neocortical
I activity and stages in a sleep-waking continuum, other
facts indicate that the correlation is not a strong one.
Previous discussions (Mirsky & Pragay 1967; Moruzzi
1972) have not brought out the full importance of these
facts for the conventional theory of arousal.
There are two main classes of phenomena which
indicate that the state of neocortical slow wave activity
(i.e., presence of LVFA, spindles, or large slow waves)
does not correlate well with arousal or consciousness as
conventionally understood. Since many of these
phenomena are well known, they can be described
briefly.
1. Examples of the first class of phenomena consist
of instances in which neocortical LVFA occurs during
natural sleep or other states of low arousal or uncon-
sciousness.
a. Active sleep is a condition in which LVFA is
prominent in animals lying in a sleeping posture and
relatively unreactive to stimuli. The musculature is
atonic but, despite this, twitches of a variety of muscle
groups occur periodically (Dement & Kleitman 1957;
Dement 1958; Jouvet 1967). The term "paradoxical
sleep" is sometimes applied to this stage, presumably
because its occurrence was puzzling in terms of the
original theory of arousal.
b. During chemically induced anesthesia, the usual
overt signs of arousal (waking posture, reactivity to
stimuli) are largely abolished. Consequently, the ortho-
dox view of arousal would suggest that large slow
waves should be present. In fact, slow waves are not
always present when an animal is anesthetized. It is
common for a form of LVFA to occur during the
surgical anesthesia produced by volatile anesthetics
such as diethyl ether or choloroform (Beecher &
McDonough 1939; Bremer 1936; Rossi & Zirondoli
1955; Vanderwolf, Kramis, Gillespie & Bland 1975). If
LVFA is absent during surgical anesthesia, stimula-
tion of the reticular formation will usually produce it,
but waking behavior will not necessarily appear
(Moruzzi & Magoun 1949).
c. Human patients in deep coma following brain-
stem injury sometimes display normal or near-normal
LVFA in the electroencephalogram (Loeb, Rosadini &
Poggio 1959). A similar phenomenon has been
observed in cats following large lesions of the basal
diencephalon (Feldman & Waller 1962) or following
transection of the pons at a midpontine pretrigeminal
level (Batini, Moruzzi, Palestini, Rossi & Zanchetti
1959).
2. The second class of phenomena consists of
instances in which large slow waves or spindles occur in
the neocortex during waking behavior.
a. A large number of investigators have shown that
slow waves and spindles frequently occur in neocortex
in normal rats and cats during such waking behaviors
as standing motionless with the head held up against
gravity and the eyes open, as well as during shivering
(rats), grooming (rats and cats), and lapping milk (cats)
(Buchwald, Horvath, Wyers & Wakefield 1964,
Grandstaff 1969; Hackett & Marczynski 1969; Marc-
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
zynski & Hackett 1969; Marczynski, Rosen & Hackett
1968; Roth, Sterman & Clemente 1967; Rougeul 1958;
Rougeul, Letalle & Crovisier 1972; Vanderwolf 1975;
Whishaw & Vanderwolf 1971). It might be supposed
that normal waking animals displaying slow wave
activity are less "aroused" or less "attentive" than they
are when displaying LVFA. However, there is no
evidence of this. The animals remain fully reactive to
sensory stimuli when the slow waves are present, show-
ing, for example, good responses to conditioned stimuli
in learning tasks (Chase & Harper 1971; Rougeul et al.
1972). Possible human analogies to this situation are
described by Larsson (1960) and Mulholland (1969),
who showed that the alpha rhythm, not LVFA, may
predominate in humans engaged in tasks requiring
concentrated attention.
If one follows the logic underlying the use of the
term "paradoxical sleep," then it would be reasonable
to use the terms "paradoxical waking" or "paradoxical
alertness" to refer to situations in which slow waves are
present in the neocortex of alert waking animals. (We
do not seriously recommend the use of these terms!)
b. Antimuscarinic drugs, such as atropine, produce
an abundance of large delta waves in the neocortex
with no evidence of sleep or coma (Longo 1966; Wikler
1952). Conversely, an anticholinesterase such as
eserine produces LVFA without producing behavioral
arousal (Bradley & Elkes 1957; Bradley & Hance 1957;
Longo & Silvestrini 1957). A variety of other drugs also
produce effects that do not conform to the orthodox
view of reticulo-cortical activity in relation to behavior.
For example, small doses of reserpine produce behav-
ioral sedation together with continuous LVFA (Jouvet
1967).
The foregoing phenomena are often accounted for
by the hypothesis that neocortical activity and arousal
are correlated under normal conditions but that some
surgical and pharmacological manipulations of the
brain destroy this correlation, producing a "dissocia-
tion" of cortical electrical activity from behavior. This
attempt to salvage the original arousal theory is unreal-
istic for several reasons. First, reticulo-cortical activity
in normal animals is not related to behavior as would
be expected on the basis of the arousal theory. Sleeping
animals may display either LVFA (active sleep) or
spindles and large amplitude slow waves (quiet sleep).
Similarly, waking animals may also display either
LVFA (during most kinds of waking behavior) or
spindles and large amplitude slow waves ("paradoxical
waking," point #2a above). Consequently, there is no
clear relation between the presence or absence of
LVFA and the occurrence of behavioral wakefulness or
sleep. Second, the statement that a drug or surgical
lesion dissociates brain activity and behavior (if it were
true) contributes little to an understanding of how such
agents affect the brain and behavior. A comprehensive
theory is required to account for the two classes of
phenomena listed above as well as many others to be
discussed below. Third, advances in anatomical tech-
niques in the past 20 years have revealed that the
"reticular formation" of the 1950s comprises a variety
of ascending or descending cholinergic and aminergic
pathways (Azmitia 1978; Lewis & Shute 1978; Linde-
vall & Bjorklund 1978). It is widely recognized that this
anatomical differentiation is probably associated with
functional differentiation as well. This suggests that the
ascending reticular formation is concerned with a vari-
ety of functions, some of which may be only indirectly
related to "arousal level" and sleep.
Finally, ablation experiments indicate that cortical
activity is irrelevant to the main phenomena of sleep.
Totally decorticate cats retain both the postures and
ocular activity characteristic of quiet sleep and the
atonia and muscular twitches characteristic of active
sleep (Villablanca & Marcus 1972). In rats, sleep
postures and a circadian rhythm of motor activity
persist following total decortication (Vanderwolf,
Kolb & Cooley 1978).
We conclude that neocortical slow wave activity is
not well correlated with arousal level or consciousness,
and further, that the states of sleep and waking are not
dependent on the integrity of the cerebral cortex or of
ascending reticulo-cortical projections.
A behavioral approach to brain function
It is commonly assumed that a major goal of brain-
behavior research is the discovery of physiological
correlates of psychological processes, including "arous-
al," "activation level," "vigilance," and the related
concepts of motivation, emotion, and drive. In this
connection it is important to distinguish clearly
between: 1) behavior, which can be defined approxi-
mately as the totality of the postures and movements
which an animal displays, and 2) psychological
processes, which cannot be known directly, and whose
existence is inferred on the basis of data obtained in
some other domain. For many authors, "arousal" seems
to be such an inferred process, one whose status can be
estimated on the basis of measuring such variables as
brain waves, muscle tension, heart rate, or skin resis-
tance (Lindsley 1951; Malmo & Belanger 1967). Other
authors who use the terms "aroused," "alert," "atten-
tive," etc., mean by them nothing more than short-
hand designations for the fact that an animal is not
comatose or asleep and is engaged in ordinary behavior
such as standing up and walking about. We approve
wholeheartedly of the intent to use descriptive termi-
nology. However, the terms to which we have referred
do not describe what animals actually do in sufficient
detail to permit valid correlations with reticulo-cortical
activity. As we shall see, it is important to know
whether animals are totally motionless or else moving
their head, walking about, chewing a piece of food,
etc.
The distinction between behavior and inferred
psychological processes is basic to a fundamental
difference of opinion on the best way to conduct
research in the brain-mind-behavior field. Many
psychologists regard behavior (in the sense intended
here) as a topic of interest chiefly insofar at it provides
a means of investigating the nature of the mind.
According to one eminent authority (Hebb 1980, p. 1)
"Mind is the central psychological problem. . . . It is
inaccurate - worse, it is misleading - to call psychology
the study of behavior." Hebb suggests that the mind
consists of the brain processes that control behavior.
THE BEHAVIORAL AND BRAIN SCIENCES (1981). 4 461
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
However, the complexity of these processes is such that
studies involving direct intervention in the nervous
system can make only limited headway. The mind
must be studied indirectly, by inference from behavior.
As a guide for research, this approach suggests that one
should: 1) study behavior in order to identify the
presence of a specific psychological process, such as
arousal, attention, motivation, or learning, then 2)
search in the brain for an anatomical, physiological, or
biochemical basis for the psychological process. It is
probable that a large part of current brain-behavior
research is guided by this point of view.
Students of behavior such as Skinner (1938, 1969,
1974) or the European ethologists (Tinbergen 1951,
1972, 1973), believe that behavior should be investi-
gated as a phenomenon in its own right and not merely
as an index of processes occurring in the mind or the
brain. As pointed out by Skinner (1950) in another
context, an investigator who is preoccupied with the
problems posed by inferred processes is likely to regard
behavior as a topic of secondary interest only and is
unlikely to describe or analyze it effectively.
A behavioristic or ethological approach is compatible
with the view that direct measures of brain activity
(electrophysiological, biochemical) can be correlated
with behavior itself without the necessity of hypothe-
sizing a psychological concept. According to this point
of view behavior should first be accurately described in
terms of posture and movement without reference to
inferred psychological processes. A level of detail must
be chosen which is appropriate to the problem being
investigated. For example, the study of spinal reflex
physiology typically requires describing muscle activ-
ity in more detail than does the study of the forebrain
control of behavior. This initial step can be followed by
an analysis of: 1) environmental or internal physiolog-
ical factors (hormones, interoceptors) that determine
the occurrence of particular behaviors, and 2) the
relations among measures of brain activity, the occur-
rence of particular behaviors, and the presence of
behavior-controlling factors such as environmental
stimuli.
If results with broad applicability are to be obtained,
it is important to study a wide range of behaviors,
especially in the early phases of investigation (Lorenz
1973; O'Keefe & Nadel 1978). Behaviors do not all
depend on the same control mechanisms and do not all
operate according to the same rules. As problems
become more clearly defined, research can be focused
on a few key areas but it is a mistake to restrict
investigation at the outset to a small number of arbi-
trarily chosen tests.
Hippocampal slow wave activity and behavior
This general approach wasfirstapplied to an investiga-
tion of the behavioral correlates of hippocampal slow
wave activity (Vanderwolf 1969; Vanderwolf et al.
1975). The hippocampus, like the neocortex, is strongly
influenced by the ascending reticular formation
(Green & Arduini 1954). Sensory stimulation, or elec-
trical stimulation of the reticular formation, produce
changes in the electrical activity throughout the cortex,
462 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
Table 1. Abbreviations used in text
ACh acetylcholine
ARAS ascending reticular activating system
CA catecholamine
CAl cornu Ammonis 1
DA dopamine
EEG electroencephalogram
LC locus coeruleus
LIA large amplitude irregular activity (hippo-
campus)
LSD-25 D-lysergic acid diethylamide
LVFA low voltage fast activity (neocortex)
NA noradrenalin
6-OHDA 6-hydroxydopamine
PGO ponto-geniculo-occipital (spike)
RSA rhythmical slow activity (hippocampus)
although the specific waveforms produced in the
neocortex are different from those in the hippocampus
(archicortex). Stimulation produces LVFA in the
neocortex but rhythmic slow activity in the hippocam-
pus (RSA; theta). Since neocortical LVFA was thought
to be correlated with arousal, and since the occurrence
of hippocampal RSA initially appeared to be correlated
with the occurrence of LVFA, the RSA waveform
came to be known as the hippocampal "arousal
rhythm."
In studying the relations of hippocampal electrical
activity to behavior, the technique initially employed
consisted simply of recording hippocampal slow wave
activity during spontaneous behavior in a small record-
ing cage or other apparatus (using manually operated
signal markers and a movement sensor). The behaviors
examined included locomotion, head movement, sniff-
ing, components of feeding, mating, grooming, swim-
ming, digging, sleep, response to various sensory stim-
uli, and performance in simple learning tasks. As far as
possible, behavior was described in terms of movement
and posture. Inferential terms such as perception,
attention, arousal, motivation, memory, and so on,
were deliberately avoided in describing the behavior of
the animals.
As work progressed it became evident that clear
correlations between slow wave activity and behavior
could be obtained only if recording electrodes were
placed correctly in the generator zones for the hippo-
campal slow waves. The critical importance of this
factor has been emphasized in a recent review (Robin-
son 1980). Since the slow wave potentials in stratum
oriens of area CAl and in stratum granulosum-molecu-
lare of the dentate gyrus are of opposite phase (Bland,
Andersen & Ganes 1975; Bland & Whishaw 1976;
Winson 1974, 1976a, 1976b), a difference recording
from electrodes placed in these areas will sum their
potentials, producing a signal with an amplitude of up
to 3 mV. Electrical activity generated by other nearby
brain structures tends to yield in-phase signals with
strongly attenuated amplitudes. By this means, it has
been possible to identify consistent relations between
behavior and hippocampal slow wave activity without
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
resorting to averaging or spectral analytical proce-
dures. Moreover, when computational methods have
been applied, in conjunction with adequate records of
behavior, they have confirmed the conclusions drawn
from visual inspection of the analogue records
(Arnolds, Lopez Da Silva, Aitink & Kamp 1979a,
1979b, 1979c; Black 1975; Coenen 1975; Morris &
Black 1978).
When adequate recordings are taken from the
hippocampus of a freely moving rat, the wave pattern
observed at a fixed electrode changes rapidly from
moment to moment in relation to concurrent behavior.
Thus, if a rat is standing motionless, head held up and
eyes fully open (alert immobility), large amplitude
irregular activity (LIA) is generally present, but RSA
appears if the rat takes a step forward. RSA is contin-
ually present when a piece of food is picked up and
carried about but it gives way to LIA if the rat pauses
for a moment and stands motionless. When eating a
large piece of solid food, rats usually hold it motionless
between their paws, squirrel-fashion, when chewing a
mouthful, but they manipulate it actively with mouth
and forepaws whenever a fresh bite is taken. Such
manipulation is accompanied by RSA, but LIA occurs
during chewing, provided that the rat is truly motion-
less (apart from respiration and the rhythmic jaw
movements). If a rat sits up to wash its face, RSA
appears briefly during the change in posture but LIA
appears during the rhythmic movements of face-
washing. If the rat then changes from face-washing to
licking the genitalia, RSA again appears briefly during
the change in posture but LIA appears during the
licking movements.
A large number of observations of this type have
suggested that rat behavior in general can be divided
into two broad classes (Fig. 2). One class - including
walking, running, swimming, rearing, jumping,
digging, and manipulation of objects with the fore-
limbs, isolated movements of the head or one limb, and
changes of posture - is always accompanied by RSA in
the hippocampus. This class has been referred to as
voluntary or Type 1 behavior. The second class of
behaviors, whose performance is ordinarily not accom-
panied by RSA, include immobility (in any posture) as
well as licking, chewing, chattering of teeth, sneez-
NORMAL RELATION OF HIPPOCAMPAl ACTIVITY TO BEHAVIOR IN THE RAT
HIPPOCAMPUS BEHAVIOR
Type I. walking, running, swimming, rearing,
jumping, digging, manipulation of objects
with the (orelimbs. isolated movements of
the head or one limb, shifts ol posture.
Related terms: voluntary, appetitive.
Instrumental, purposive, operant, or "theta"
behavior.
Type 2. a) aleri immobility in any posture.
t>) licking, chewing, chattering the teeth,
sneezing, startle response, vocalization,
shivering, tremor, face-washing, scratching
the fur, pelvic thrusting, ejaculation, defecation,
urination, piloerection.
Related terms; automatic, reflexive, consummatory.
respondent, or "non-theta" behavior.
Figure. 2. Normal relation of hippocampal activity to
behavior in the rat. Upper record, RSA; lower record LIA.
(From Vanderwolf et al. 1975, with permission.)
ing, the startle response, vocalization, shivering,
tremor, face-washing, scratching the fur, pelvic thrust-
ing, ejaculation, defecation, urination, and piloerec-
tion. Many of the behaviors in this class have a
relatively simple reflexive or consummatory character
and have been referred to as automatic or Type 2
behavior (defined as behavior with no consistent rela-
tion to RSA). If behaviors of the two groups occur
simultaneously, RSA also occurs. For example, a short
burst of RSA appears against a background of LIA if a
rat changes posture while licking water continuously
from a dish.
A major finding was that RSA is correlated with
overt behavior in itself rather than with the environ-
mental circumstances or the psychological processes
which might be assumed to cause the behavior. Thus,
locomotion is always accompanied by RSA regardless
of whether it occurs in a novel environment ("explora-
tion"); as a result of food deprivation, treatment with
amphetamine, or pinching of the tail; or following
training to obtain food or avoid shock in tests of
operant behavior. RSA also persists if rats are forced to
walk for hours in a motor driven treadmill or trained to
jump out of a box several thousand times in quick
succession (Vanderwolf & Cooley 1974; Whishaw &
Vanderwolf 1973). If a drowsy rat changes posture, for
example, changing from a position of lying on the left
side to lying on the right side, RSA accompanies the
movement although the eyes remain closed. On the
other hand, behavioral immobility is accompanied by
LIA in most conditions reagardless of the level of
"arousal" or "excitement" a human observer might
attribute to the rat. Thus, LIA is observed when a rat is
motionless, resting quietly on the floor, but it is also
observed when the rat has just received a strong electric
shock to the feet which (after an initial violent scram-
ble accompanied by RSA) causes it to stand motionless
with its hair erect, its eyes protruding slightly, and its
teeth chattering loudly. Further, during fighting, LIA
is present in a rat while it is being bitten by another rat,
provided that it remains motionless (Frederickson,
Miczek, Zurawin & Frederickson 1977).
A further point is that RSA does not seem to be a
result of proprioceptive or cutaneous feedback from
the accompanying movements since it is not abolished
by curarization and is not produced by a purely passive
movement imposed by the experimenter. Thus, RSA
may play some role in the control of motor activity.
Since RSA can be generated by stimulation of the
reticular formation and can be totally abolished by
interruption of reticulo-septo-hippocampal pathways,
its occurrence under physiological conditions is proba-
bly due to increased activity in the ascending reticular
formation (Green & Arduini 1954; Brugge 1965).
Therefore, the behavioral data suggest that there is a
reticulo-hypothalamo-septo-hippocampal pathway
which becomes more active if, and only if, Type 1
behavior is being performed.
Two types of RSA
A major complication with the simple picture outlined
thus far is the fact that RSA is very prominent in some
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 463
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
circumstances when animals are largely or entirely
motionless. Rats anesthetized with urethane, ethyl alco-
hol, or volatile anesthetics (ether, chloroform, ethylene
chloride) show long trains of RSA spontaneously or in
response to sensory stimuli. Movement, of course, is
absent in this condition. In some species, RSA is promi-
nent in the absence of movement even in the normal
waking state (Harper 1971; Kramis, Vanderwolf &
Bland 1975; Robinson, 1980; Winson 1972). For exam-
ple, if a rat is startled by the sound of a sudden
handclap when it is lying down quietly, it is likely to
leap to its feet, then stand motionless with its eyes
opened widely. A hippocampal recording made during
this behavior shows either continuous LIA or a transi-
tion from LIA (accompanying the behavior of lying
motionless) to a pattern of small amplitude irregular
activity (SIA). RSA is not observed unless the rat makes
additional head movements or runs away. In contrast,
with a rabbit, a sudden handclap will produce a long
train of RSA even though the animal remains perfectly
motionless, apart from a brief startle response. Such
observations, plus similar ones made in cats, have led to
a good deal of controversy concerning the behavioral
correlates of hippocampal RSA (Bennett 1975; Cole-
man & Lindsley 1975; Kemp & Kaada 1975; Klemm
1976).
A solution to these problems is provided by evidence
that RSA is not a unitary phenomenon (Fig. 3). If a
waking rabbit is given atropine SO4 (5 mg/kg, i.v.) all
traces of RSA during behavioral immobility or face-
washing quickly vanish but the RSA accompanying
head movements, postural changes, and hopping
persists almost unchanged. Thus the relations of RSA to
behavior in an atropine-treated rabbit are very similar
to those seen in an undrugged rat; RSA occurs if, and
only if, certain motor patterns occur (Kramis et al.
1975). Like rats, rabbits display RSA when they are
anesthetized with urethane, ethyl alcohol, or volatile
anesthetics. Such RSA is abolished readily by an injec-
tion of atropine SO4 (Kramis et al. 1975; Vanderwolf,
Kramis & Robinson 1978; Whishaw 1976). Thus, RSA
occuring in rabbits during behavioral immobility in the
anesthetized as well as during the unanesthetized state
is sensitive to atropine. The RSA which accompanies
face-washing in rabbits is also sensitive to atropine.
NO ATROPINE
NO
ETHEf
I^VM' 1 ' 1 !!'!!!!,'' 1 1 ! ''''iii1')1"'1''!!)
Av*
immobile walking
Figure. 3. Hippocampal slow wave activity under four
conditions. (1) Undrugged state; (2) after atropine SO4 (50
mg/kg, i.p.); (3) during ether anaesthesia, (4) during ether
anaesthesia after atropine SO4 (50 mg/kg, i.p.). Note: low
frequency RSA during anaesthesia, higher frequency RSA
during walking, and total absence of RSA if atropine is
combined with anaesthesia. (From Vanderwolf et al. 1978,
reprinted with permission of Excerpta Medica.)
464 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
However, the RSA accompanying Type 1 behavior is
resistant to this drug.
Comparable effects occur in rats. It has been known
for several years that the RSA accompanying Type 1
behavior in rats is not abolished, even by extremely
large doses of atropine (up to 150 mg/kg, i.p.) or
scopolamine (10 mg/kg, i.p.) (Vanderwolf, Bland &
Whishaw 1973; Vanderwolf 1975). In contrast, the RSA
occuring during anesthesia (induced by volatile anes-
thetics, alcohol, or urethane) is abolished by atropinic
drugs. If atropine is administered first, followed by a
volatile anesthetic, RSA ceases to appear at approxi-
mately the same time that struggling movements cease.
Therefore, it appears that the RSA component which is
resistant to atropine is sensitive to anesthetics (Kramis
et al. 1975; Vanderwolf et al. 1975; Vanderwolf et al.
1978; Whishaw 1976). This suggests that there are not
one, but two distinct reticulo-hippocampal pathways,
each capable of producing RSA. One pathway, resis-
tant to atropine but sensitive to anesthetics, is active in
waking rats and rabbits only in relation to the occur-
rence of Type 1 behavior. The second pathway, sensi-
tive to atropine but resistant to volatile anesthetics, can
be active during waking immobility, especially in
rabbits. The existence of two such pathways has
recently been confirmed by a study of hippocampal
rhythms evoked by rhythmic bursts of electrical stimu-
lation of the medial septum (Kramis & Vanderwolf
1980).
The atropine-sensitive and anesthetic-sensitive com-
ponents of RSA differ in mean frequency although
there is some overlap in the two frequency distribu-
tions. In both rats and rabbits the RSA accompanying
Type 1 behavior ranges in frequency from about 7-12
Hz while the RSA which sometimes accompanies
waking immobility or other Type 2 behavior usually
has a frequency of about 6 Hz. In the anesthetized state
RSA frequency may be as low as 4 Hz.
Another line of evidence which suggests that RSA
does not constitute a unitary phenomenon comes from
studies of the ontogeny of hippocampal electrical activ-
ity (Creery & Bland 1980). By 8 days of age rabbits
show the correlation between Type 1 behavior and
RSA characteristic of the adult. However, the lower
frequency RSA induced (in the absence of Type 1
behavior) by sensory stimulation or an anticholinester-
ATROPINE ase drug does not develop until the rabbit is 14 days of
age. The differences in the rate of development of the
fl|il|'*|f|!l( 1.0
two types of RSA may be due to differences in the
mV
im mobile * walking ontogenesis of two different neurotransmitter systems
involved in the generation of RSA.
Atropine-sensitive RSA may result from activity in a
retieulo-septo-hippocampal pathway which contains
muscarinic cholinergic synapses at one or more points.
Evidence favoring this hypothesis is based mainly on
studies using systemic administration of drugs, a
method that raises many problems of interpretation.
However, it has been shown that the RSA occurring
during Type 2 behavior or anesthesia, which is sensi-
tive to atropine or scopolamine, is not abolished by a
variety of other drugs, including reserpine, nicotinic
blockers such as mecamylamine, various antipsychotic
drugs, enzyme blockers such as a-methyl-p-tyrosine
and p-chlorophenylalanine as well as various anes-
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
thetics (Assaf & Miller 1977; Vanderwolf et al. 1978).
Further, the injection of cholinergic agonists (acetyl-
choline, eserine, diisopropylfuorophosphate) by a vari-
ety of routes (including intracarotid injections)
produces long trains of RSA without producing behav-
ioral activation, i.e., without producing Type 1 move-
ment (Monnier & Romanowski 1961; Sailer & Stumpf
1957; Bradley & Nicholson 1962; Torii & Wikler 1966;
Vanderwolf 1975). Such RSA can be abolished by a
subsequent injection of atropine.
An additional piece of evidence which supports the
concept of a cholinergic pathway producing RSA
during Type 2 behavior and anesthesia is the recent
finding of Robinson & Green (1980) that intraventricu-
lar injections of hemicholinium, which deplete brain
acetylcholine (ACh), abolish RSA in urethane-anesthe-
tized rats. The RSA accompanying Type 1 behavior in
freely moving rats is unaffected, supporting the
hypothesis that a noncholinergic pathway is active in
producing RSA in association with such behavior.
A probably anatomical and biochemical basis for the
production of "cholinergic" RSA has been described in
a series of studies of cholinergic reticulo-septo-hippo-
campal pathways (Kuhar 1975). The evidence for such
pathways includes the demonstration of reticulo-
septo-hippocampal fibres containing acetylcholinester-
ase (Lewis & Shute 1967). Recent studies using immu-
nohistochemical methods have shown that cells in the
medial septum and diagonal band contain not only
acetylcholinesterase, but choline acetyltransferase as
well (Kimura, McGeer, Peng & McGeer 1980). Septal
lesions result in a loss of choline acetyltransferase
activity in the hippocampus, suggesting that some
septo-hippocampal fibres contain this enzyme (Lewis,
Shute & Silver 1967). High-affinity uptake of choline
and the acetylcholine content of the hippocampus are
also reduced by septal lesions (Kuhar, Sethy, Roth &
Aghajanian 1973). Thus, there appear to be septo-
hippocampal fibres which take up choline and which
possess the apparatus for the manufacture, storage, and
destruction of acetylcholine. Stimulation of the septal
nuclei or the reticular formation (Smith 1972; Dudar
1975) results in a release of acetylcholine from the
hippocampus. Since muscarinic receptors appear to be
present in the hippocampus (Biscoe & Straughan 1966;
Yamamura, Kuhar & Snyder 1974), such released
acetylcholine might be expected to have postsynaptic
effects, including the generation of RSA. Ott, Malish &
Krug (1977) have shown that RSA can be produced by
the injection of a cholinergic agonist (oxotremorine)
directly into the hippocampus. However, since hemi-
cholinium may block hippocampal RSA when it is
injected into the hypothalamus there may be choliner-
gic neurons involved in RSA production at this site as
well (Friedman & Wikler 1970).
It is curious that the RSA occurring during anesthesia
or Type II behavior in the waking state can be
abolished by atropine (base), atropine SO4, or scopol-
amine HBr only with relatively large doses. In neither
rats nor rabbits are intravenous doses of atropine SO4 of
less than about 5 mg/kg consistently effective. With
intraperitoneal injection in rats, a dose of about 25
mg/kg is required. Similarly, Yamamura, Kuhar &
Snyder (1974) showed at atropine must be given in
doses of 25-50 mg/kg to produce an extensive occupa-
tion of muscarinic cholinergic receptor binding sites in
rat brain. Such doses are considerably larger than those
required to block peripheral muscarinic synapses. The
high doses necessary for effects on the brain are at least
partly due to the fact that atropine or atropine SO4 do
not penetrate the brain nearly as well as they penetrate
other tissues (Albanus, Hammarstrom, Sundwall,
Ulberg & Vangbo 1968; Albanus, Sundwall, Vango &
Windbladh 1968; Gosselin, Gabourel, Kaiser & Wills
1955; T^nnesen 1948). Further, the data of Whishaw,
Bland & Bayer (1978) on the effects of X-irradiation of
neonatal rats on subsequent development of hippocam-
pal RSA suggest that normal rhythms may persist even
when only a fraction of the normal cell population is
capable of activity. Thus, atropine may abolish immo-
bility-accompanying RSA only when it is present in
concentrations large enough to block virtually all react-
ing cells.
If atropine-sensitive RSA is dependent on activity in
cholinergic synapses, an obvious question is raised.
What neurotransmitter system(s) is necessary to
produce atropine-resistant RSA? It has been suggested
that catecholaminergic neurons ascending from the
locus coeruleus may be involved in the production of
RSA, since stimulation of the locus coeruleus has been
reported to produce RSA in cats (Macadar et al. 1974).
This suggestion is supported by studies on the effects of
adrenergic drugs on hippocampal electrical activity.
Intracarotid injections of adrenaline or noradrenaline
(NA) (Kawamura and Oshima 1962), or systemic injec-
tions of amphetamine produce hippocampal RSA
(Bradley & Nicholson 1962; Longo 1962; Stumpf, 1965;
Vanderwolf 1975).
The neuroanatomical basis for a role of the locus
coeruleus in the modulation of hippocampal activity
has been well documented with a variety of techniques
(see Moore 1975 for review). Fluorescence histochemi-
cal and immunohistochemical studies have revealed
that noradrenaline-containing (or dopamine /3-hy-
droxylase-containing) cells in the locus coeruleus give
rise to fibers which ascend via the median forebrain
bundle to innervate the hippocampus. Locus coeruleus
or medial forebrain bundle lesions greatly reduce the
NA histofluorescence (Ungerstedt 1971) and assayed
NA levels in the hippocampus (Kobayashi et al. 1974).
In addition, hippocampal pyramidal cells usually
respond to micro-iontophoretically applied NA with a
long latency, long duration inhibitory response (Biscoe
& Straughan 1966; see Straughan 1975 for review). The
inhibitory effect of NA is blocked by a /3-adrenergic
antagonist and facilitated by desmethylimipramine,
which prevents NA re-uptake (Segal & Bloom 1974).
Lastly, the hippocampus contains /3-adrenergic recep-
tors (Melamed et al. 1977).
However, further studies strongly suggest that NA is
not important for the production of hippocampal RSA.
In rats, electrical stimulation of the locus coeruleus is
ineffective in producing hippocampal RSA, except at
very high current intensities (Robinson et al. 1977;
Robinson & Vanderwolf 1978; M. Segal, personal
communication). Earlier reports (Macadar et al. 1974
that stimulation of the locus coeruleus does produce
RSA may have been due to current spread to the
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 465
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
underlying reticular formation. Stimulation of the
reticular substance just ventral to the locus coeruleus is
very effective in producing RSA (Robinson et al. 1977).
In addition, atropine-resistant RSA, which is correlated
with Type 1 behavior, fails to be abolished by a variety
of treatments that deplete brain NA, including: 1)
systemic neonatal injections of 6-hydroxydopamine (6-
OHDA; Robinson et al. 1977); 2) systemic injections of
a-methyl-p-tyrosine or FLA-63 (Robinson et al. 1977);
or 3) intraventricular injections of 6-OHDA in adult
rats (Whishaw et al. 1978). Electrolytic lesions of the
locus coeruleus also fail to abolish atropine-resistant
RSA (Kolb and Whishaw 1977). Since some of these
treatments also severely deplete brain dopamine (e.g.,
a-methyl-p-tyrosine or intraventricular 6-OHDA) it is
unlikely that either catecholamine is necessary for the
production of atropine-resistant RSA.
Thus, the neurotransmitter(s) involved in a noncho-
linergic reticulo-hippocampal pathway responsible for
the production of RSA in association with Type 1
behavior, remain unknown. [According to C. Destrade
and T. Ott, (personal communication) glutaminergic
synapses may be involved.]
Neocortical activation and behavior:
Cholinergic influences
A good deal of evidence from early studies suggests
that acetylocholine (ACh) is also involved in the
production of neocortical LVFA. The injection of ACh
or other cholinergic agonists by a variety of routes,
including local application to the cortical surface, abol-
ishes large amplitude slow waves or produces neocorti-
cal LVFA (Bonnet & Bremer 1937; Bremer & Chaton-
net 1949; Miller, Stavraky & Woonton 1940; Monnier
& Romanowski 1961). Low rates of ACh release from
the neocortical surface have been shown to be asso-
ciated with large slow waves during slow wave sleep,
following brainstem transection, and during chloralose
or barbiturate anaesthesia, whereas high rates of ACh
release and LVFA tend to occur together in the waking
state and in active sleep (Celesia & Jasper 1966; Jasper
& Tessier 1971; Kanai & Szerb 1965; Sie, Jasper &
Wolfe 1965; Szerb 1967). It is interesting that volatile
anaesthetics, which permit the occurrence of a good
deal of LVFA, also permit higher rates of ACh release
than such anaesthetics as chloralose and barbiturates,
which modify or abolish LVFA (Phillis 1968). Lastly,
there is an extensive literature claiming that choliner-
gic antagonists, such as atropine and scopolamine,
abolish LVFA, resulting in an animal that emits contin-
uous slow waves (Bradley & Elkes 1953, 1957; Funder-
burk & Case 1951; Montplaisir 1975; Rinaldi &
Himwich 1955; Torii & Wikler 1966; Wikler 1952).
The effects of ACh on neocortical electrical activity
may very well be mediated by the "ascending choliner-
gic reticular formation" described by Shute & Lewis
(1967). This system of ascending reticulo-cortical fibers
contains acetylcholinesterase (Shute & Lewis 1967;
Jacobowitz & Palkovits 1974), may contain choline
acetyltransferase (Hebb, Krnjevic & Silver 1963; Hoov-
er, Muth & Jacobowitz 1978), and is, therefore, thought
to contribute a diffuse cholinergic input to the neocor-
466 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
tex (Krnjevic 1974; Phillis 1976). Strong evidence for
an ascending cholinergic activating system is provided
by studies which show that electrical stimulation of the
midbrain reticular formation increases the rate of ACh
release from the neocortical surface and produces
LVFA (Kanai & Szerb 1965; Szerb 1967). Many
neocortical cells have been shown to be cholinoceptive
(for reviews see Phillis 1974, 1976). Post-synaptic
effects of ACh on these cells may be mediated by
muscarinic receptors, which have been shown to be
located on cortical neurons (Krnjevic & Phillis 1963a,
1963b; Yamamura, Kuhar, Greenburg & Snyder 1974;
Yamamura et al. 1974).
Taken together all these data provide strong
evidence that the "cholinergic reticular formation"
plays an important role in controlling neocortical acti-
vation. Therefore, in the context of the traditional
arousal theory, it is surprising that antimuscarinic
drugs such as atropine result in the appearance of
extensive large amplitude slow wave activity in an
apparently alert active animal.
Consequently, it appeared to us, worthwhile to rein-
vestigate the effects of atropine in rats, using the same
behavioral methods which had proved successful in
work on the hippocampus. During the course of the
atropine studies it was found that the location of the
recording electrodes plays a key role in the type of data
obtained (Fig. 4). Conventional bipolar screw elec-
trodes do not reveal clearly some of the effects of
atropine on neocortical activity. The reason for this is
that the large slow waves produced by atropine are
Figure. 4. Slow wave activity in the parietal neocortex of a
rat following atropine SO4 (50 mg/kg) and trifluoperazine (10
mg/kg) injection. LSD, left surface-to-depth bipolar lead;
RSD, right surfact-to-depth bipolar lead; RD, monopolar
record from right cortex 1 mm below surface; RS, monopolar
record from right cortical surface. In surface-to-depth elec-
trode pairs an upward deflection indicates relative negativity
at deep electrodes. In monopolar leads an upward deflection
indicates negativity at the active lead (with respect to an
indifferent referent in the skull over the cerebellum). Left
panel. Note large slow waves during immobility and low
voltage fast waves during struggling induced by handling.
Changes are especially clear in SD derivations. Right panel.
Note that: (a) activity in right and left cortices is closely in
phase, and (b) activity at surface and deep sites in the right
cortex tends to be of opposite phase. Time marks indicate 1
and 5 sec intervals. (From Vanderwolf & Pappas, 1980;
reprinted with permission of Elsevier/North-Holland Bio-
medical Press.)
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
closely in phase over wide areas of neocortex within a
hemisphere, and waves in one hemisphere are in phase
with those in the other. Consequently, bipolar screw
electrodes will be exposed to in-phase signals which
will largely be rejected by the differential amplifiers
generally used in laboratories. Monopolar records
taken from the pial surface (used, for example by
Bradley & Elkes 1953) also do not reveal the relations
to behavior very clearly, although they are obvious in
monopolar records taken from a point about 1 mm
below the pial surface. Slow waves recorded monopo-
larly from the pial surface tend to be phase-reversed
with respect to the large waves recorded monopolarly
about 1 mm below the surface (Schaul, Gloor, Ball &
Gotman 1978). Consequently, a bipolar surface-to-
depth recording yields slow waves of especially large
amplitude (often 2 mV) while rejecting the largely
in-phase signals from other sources, such as the hippo-
campus. Using such electrodes it is possible to demon-
strate clearly phenomena which are revealed only
imperfectly (or not at all) by electrodes placed on the
mopial surface (Figs. 4 & 5).
When the relation of neocortical activity to behavior
was studied in normal undrugged rats it was observed
that LVFA was invariably present during head move-
ment, locomotion, and other behavior of the type
normally associated with hippocampal RSA. LVFA is
also usually present during the occurrence of many
waking behaviors not normally associated with RSA,
CONTROL
A CORTEX
BEHAVIOR /
h h > an atropine dose of about 25 mg/kg, LVFA virtually
ATROPINE
f'l^^^^^^-^ljt
Figure 5. Neocortical slow wave activity in relation to
behavior in a rat. A: control record after trifluoperazine H Cl
(5 nig/kg, i.p.); B: after addition of atropine SO4 (50 mg/kg,
i.p.); C: low speed record after trifluoperazine and atropine.
h, head movement; S, stepping. Note relation between slow
waves and motor activity in B and C. Trifluoperazine coun-
teracts the excessive motor activity produced by atropine.
(From Vanderwolf et al. 1978, reprinted with permission of
Excerpta Medica.)
such as alert immobility, face washing, licking or biting
the fur, gnashing the teeth, chewing food, or drinking
water. However, at times, especially during prolonged
periods of alert immobility with the head held up and
the eyes open ("freezing"), LVFA may suddenly give
way to 6-9 Hz rhythmical spindle activity, which often
assumes a spike-and-wave pattern with an amplitude
up to 2 mV (Klingberg 1971; Semba et al. 1980;
Vanderwolf 1975). These waves are frequently accom-
panied by a rapid tremor of the vibrissae and head but
they never occur during even slight head movements
of the type displayed during exploratory scanning,
searching for food, etc., or during any other Type 1
behavior. Mild sensory stimuli or stimulation of the
reticular formation also readily abolish these waves.
Spontaneous 6-9 Hz spindle activity can be recorded
in a wide area of neocortex in the rat. However, it is
morphologically similar to the rhythmic afterdischarge
localized to striate cortex following a light flash
(Kimura 1962). The flash-triggered afterdischarge, like
the spontaneous spindle activity, has a relation to
behavior which is reminiscent of the relation of hippo-
campal RSA to behavior in a waking normal rat. Thus,
Pickenhain & Klingberg (1965) observed that rhythmic
afterdischarges can be evoked in waking rats during
immobility or grooming behavior but not during loco-
motion.
Small doses of atropine SO4 (0.1-1.0 mg/kg, i.p.)
produce no clear change in the normal patterns of
neocortical activity but a larger dose (5.0 mg/kg)
results in occasional bursts of large amplitude slow
wave activity; these occur only during behavioral
immobility. Such large slow waves occur in a pattern
similar to the one observed during natural slow wave
sleep, as originally noted by Funderburk & Case (1951;
cf. Montplaisir 1975). Doses larger than 5 mg/kg
increase the occurrence of these large slow waves. At
ceases to occur during periods of immobility but it
persists during head movement, walking, rearing,
struggling when held, and other Type 1 movements
(Vanderwolf 1975). Such persisting LVFA can be
referred to as atropine-resistant LVFA since it is unaf-
fected by doses of atropine as large as 150 mg/kg. The
large slow waves produced by atropine occur during
such behaviors as tremor or chattering of the teeth, just
as they do during total immobility. During face-
washing LVFA accompanies the postural changes
involved in sitting up on the hind legs and the initial
part of the face-washing sequence. However, if face-
washing persists for several seconds without noticeable
changes in posture, large slow waves appear. Thus, the
occurrence of LVFA in an atropinized rat is associated
with the same general type of behavior as that asso-
ciated with RSA in an undrugged rat. A further parallel
with RSA is observed in the finding that a purely
passive movement (imposed by the experimenter) is
not associated with atropine-resistant LVFA. This
suggests that atropine-resistant LVFA is not due to
proprioceptive feedback from moving body parts, a
conclusion which is supported by the fact that the wave
pattern continues to occur spontaneously in rats that
are curarized (Whishaw, Bland, Robinson & Vander-
wolf 1976). Presumably, atropine-resistant LVFA
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 467
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
would remain correlated with action potentials in the
motor nerves of curarized animals, but this point has
never been examined.
The presence of large amplitude slow waves in the
neocortex of a motionless rat might be regarded as an
indication of inattention or even of sleep. However,
immobility may sometimes be a sign of arousal and
attention. If an active atropinized rat is startled by a
handclap or another sudden stimulus it will sometimes
stand absolutely motionless for several seconds (freez-
ing behavior), usually facing the source of the stimulus.
On other occasions the sudden stimulus may be
followed by an increase in head movements, stepping,
and sniffing. Both types of reaction might equally be
regarded as indicative of arousal or attention but,
nonetheless, they are correlated with different patterns
of slow waves. Freezing behavior in this situation is
invariably associated with large slow waves while head
movements and stepping are associated with LVFA.
Thus neocortical slow wave activity in an atropinized
rat is more closely correlated with overt behavior than
with inferred processes such as attention or arousal.
Further, the relations of slow wave activity to behavior
are identical in a situation involving shock avoidance
performance and one involving spontaneous behavior
on a small open platform (Vanderwolf 1975). It there-
fore appears that the neocortical activation accom-
panying a given behavior is similar regardless of
whether the behavior occurs spontaneously or as a primarily from studies involving pharmacological
result of training.
If an atropinized rat is anesthetized with a volatile
anesthetic such as diethyl ether or trichloroethylene,
the atropine-resistant LVFA disappears at approxi-
mately the same level of anesthesia that struggling
movements cease. It cannot then be elicited at all, even
by painful peripheral stimulation or by strong stimula-
tion of the reticular formation. If the anesthetic agent is coeruleus (and surrounding area) depresses "electro-
given first, the LVFA which normally occurs during
anesthesia produced by volatile anesthetics can be cal waking" is correlated with the loss of forebrain NA
abolished by a subsequent injection of atropine (Van-
derwolf, Kramis, Gillespie & Bland 1975). Similar
effects can be demonstrated using large doses of ethyl
alcohol as an anaesthetic agent (Whishaw 1976).
These results suggest that neocortical LVFA, like
hippocampal RSA, is controlled by two independent
inputs from the reticular formation. A cholinergic
reticulo-cortical pathway is probably responsible for an
atropine-sensitive form of LVFA which occurs during
immobility and other Type 2 behavior in waking
animals and can also occur during the surgical anes-
thesia produced by volatile anesthetics. As would be
expected, it is possible to activate this pathway by an
injection of eserine without producing concomitant
motor activity (Bradley & Elkes 1957; Bradley &
Hance 1957; Longo & Silverstrini 1957). In addition to such experiments.
this presumed cholinergic pathway, there is a second
type of reticular formation input to the neocortex
which is resistant to atropine but sensitive to the action
of volatile anesthetics and alcohol. This input appears
to be active during, and only during, such behaviors as
walking, spontaneous changes in posture, head turning,
or struggling when held (Type 1 behavior). Presum-
ably, it is this atropine-resistant input which is responsi- produce a behavioral state of catalepsy and akinesia in
ble for the fact that LVFA is invariably present during
468 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
Type 1 behavior in a normal undrugged rat. It may
also be responsible for the suppression of flash-
triggered afterdischarges during Type 1 behavior, as
described by Pickenhain & Klingberg (1965).
Neocortical activation and behavior:
Monoaminergic influences
Numerous investigations have indicated that brain
monoaminergic systems may play a role in the activa-
tion of the neocortex. Some experiments have
suggested that adrenalin or noradrenalin may be a
transmitter in the ascending reticular formation (Cor-
deau, Champlain & Jacks 1971; Dell 1958; Rothballer
1956). Other studies have not favored this hypothesis
(Baust, Niemczyk & Vieth 1971; Mantegazzini, Poeck
& Santibanez 1959). However, the idea that ascending
norandrenergic fibers may be involved in neocortical
activation was revived with the discovery of diffuse
noradrenergic projections from the locus coeruleus to
the hippocampus and neocortex (Anden, Dahlstrom,
Fuxe, Larsson, Olson & Ungerstedt 1966).
Jouvet has been the most vigorous proponent of the
idea that the ascending NA projections from the locus
coeruleus are important for the electrocortical activa-
tion occurring during waking (Jouvet 1972, 1974,
1977). The evidence to support this idea is derived
manipulations or lesions of the locus coeruleus; it
includes the following: 1) Increasing the brain levels of
catecholamines (CA) by administrating L-dopa causes
behavioral and EEG arousal; 2) depletion of brain CA
causes a decrease in the behavioral and EEG arousal
which usually follows amphetamine administration; 3)
destruction of the ascending NA fibers from the locus
cortical waking," and this depression of "electrocorti-
(Jones, Bobillier, Pin & Jouvet 1973). On the basis of
these studies, Jouvet and his collaborators have
concluded that brainstem NA neurons are important in
mediating "tonic cortical activation" during waking
behaviors. This hypothesis has received support from a
number of other researchers using similar procedures
(Bolme, Fuxe & Lidbrink 1972; Fuxe, Hokfelt &
Ungerstedt 1970; Fuxe, Lidbrink, Hokfelt, Bolme &
Goldstein 1974; Lidbrink 1974). For example, Lidbrink
(1974) reported that injections of 6-OHDA into the
locus coeruleus depleted forebrain NA and produced a
correlated decrease in waking time (determined elec-
troencephalographically). It may be necessary to
repeat at this point that the occurrence of LVFA should
not be equated with "waking" in a behavioral sense in
The hypothesis that a monoamine (but not a cate-
cholamine; see below) is directly involved in neocorti-
cal activation is supported by a recent series of experi-
ments which have made use of reserpine and other
drugs as a means of altering brain monoamine function
(Vanderwolf & Pappas 1980; Vanderwolf, Robinson &
Pappas 1980). Large doses (10 mg/kg) of reserpine
rats, as is well known (Bein 1956). Spontaneous neocor-
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
tical activity accompanying this state consists of peri-
ods of rather irregular large slow waves resembling
those of natural slow wave sleep, or of rhythmic spin-
dles resembling the 6-9 Hz spindles which occasionally
occur in normal rats. LVFA of normal appearance
occurs spontaneously at times or can be elicited by
natural stimuli, such as stroking the fur, or by stimulat-
ing the midbrain reticular formation. LVFA can occur
during total behavioral immobility as well as during
episodes of head movement or attempts to walk. If
atropine (25-50 mg/kg, i.p.) is administered 12-24 hr
after the reserpine, all LVFA usually disappears. Even
painful peripheral stimuli or strong stimulation of the
midbrain reticular formation or hypothalamus - which
all produce vigorous motor activity - fail to alter the
continuous pattern of large irregular slow waves, which
resemble those that occur in a motionless nonreserpi-
nized rat following treatment with atropine. Thus, it
appears that reserpine abolishes the atropine-resistant
LVFA which normally accompanies Type 1 motor
activity (Fig. 6).
It is well known that large doses of reserpine produce
a severe depletion of eateeholamines and 5-hydroxy-
tryptamine in the brain and other tissues. This deple-
tion occurs as a result of inhibition of uptake of the
amines by intracellular storage granules, which thereby
increases exposure to mitochondrial monoamine
oxidase (Kirschner 1962; Kopin 1972). However, reser-
pine also affects a variety of nonmonoaminergic
PIMOZIDE + ATROPINE
MOVEMENT SENSOR
RESERPINE + ATROPINE
Figure 6. Neocortical slow wave activity in a rat following
the administration of reserpine (10 mg/kg) plus atropine (50
mgAg) o r pimozide (5 mg/kg) plus atropine (50 mg/kg).
Upper traces: One hr after pimozide injection and 30 min
after atropine, rat is severely cataleptic but makes occasional
spontaneous head movements which are associated with low
voltage fast activity (LVFA). Walking and struggling are also
associated with LVFA but large slow waves occur during
immobility. Lower traces: Same rat 24 days later. Forty-eight
hr after reserpine injection and 30 min after atropine, rat
displays moderate spontaneous activity, moving the head,
stepping, and walking. LVFA is absent. Time marks indicate
1 and 5 sec intervals. (From Vanderwolf & Pappas 1980;
reprinted with permission of Elsevier/North-Holland Bio-
medical Press.)
compounds in the nervous system, including histamine
(Adam & Hye 1966) and various amino acids (Santini
& Berl 1972). Consequently, the observation that atro-
pine-resistant LVFA is sensitive to reserpine need not
indicate that a monoamine is involved in its produc-
tion.
More definitive evidence that a monoamine plays a
key role in the production of atropine-resistant LVFA
is provided by the observation that the reserpine-
induced blockade of atropine-resistant LVFA can be
prevented by prior treatment with a monoamine
oxidase inhibitor (nialamide, 50 mg/kg). This shows
that the reserpine-induced blockage can occur only in
the presence of uninhibited monoamine oxidase.
Therefore, it appears that some compound which is
essential for the appearance of atropine-resistant
LVFA is a substrate of monoamine oxidase. Known
substrates of monoamine oxidase which are normally
present in the brain include noradrenalin, dopamine,
serotonin, and various trace amines such as /3-phenyl-
ethylamine, tyramine, and octopamine.
The possible role of a number of these amines in
producing atropine-resistant LVFA has been assessed
by several different procedures. It is quite unlikely that
the unknown amine essential for the occurrence of
atropine-resistant LVFA is either dopamine or nora-
drenalin. Atropine-resistant LVFA in rats is not abol-
ished by: (a) depletion of neocortical noradrenalin by
neonatal systemic injection of 6-OH dopamine (Robin-
son, et al. 1977); (b) depletion of noradrenaline and
dopamine together by intraventricular injection of 6-
OH dopamine in adults (Whishaw, Robinson, Schallert,
DeRyck & Ramirez 1978); (c) blocking the synthesis of
dopamine and noradrenalin by means of «-methyl-
p-tyrosine or blocking the synthesis of noradrenalin
alone by means of FLA-63 (Robinson, et al. 1977); (d)
treatment with catecholamine receptor blockers such
as chlorpromazine, trifluoperazine, haloperidol, phen-
oxybenzamine, pimozide, and propranolol (Vander-
wolf et al. 1978; Vanderwolf & Pappas 1980).
The conclusion that NA is not important for the
production of neocortical LVFA is further supported
by recent studies in which the locus coeruleus was
destroyed (see Jacobs & Jones 1978, for review). Jones
et al. (1977) reported that lesions of the locus coeruleus,
severely depleting forebrain NA, do not significantly
disrupt EEG activation in cats. Kolb & Whishaw (1977)
reported that after locus coeruleus lesions in rats, both
atropine-sensitive and atropine-resistant LVFA were
present, and the latter showed its normal relations to
ongoing motor behavior.
The results reviewed above provide strong evidence
that the eateeholamines are not essential for the gener-
ation of either atropine-sensitive or atropine-resistant
LVFA in the neocortex. Serotonin is probably likewise
of little importance in this function. Blocking the
synthesis of serotonin with p-chlorophenylalanine does
not abolish atropine-resistant LVFA. Suppressing the
activity of central serotonergic neurons with LSD-25 is
also ineffective, as is treatment with presumed seroton-
ergic receptor blocking drugs such as methysergide
bimaleate.
A different approach to the problem has been
suggested by the possibility of restoring amines selec-
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 469
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
tively, after their depletion by reserpine. Using this
technique, Carlsson, Lindqvist & Magnussen (1957)
showed that restoring catecholamines by 1-dopa treat-
ment reversed the catalepsy and akinesia produced by
reserpine. 5-Hydroxytryptophan was ineffective. This
provides strong evidence that reserpine-induced cata-
lepsy is due to depletion of catecholamines. Applying
this method to the identification of the amine involved
in atropine-resistant LVFA showed that 1-dopa does not
restore atropine-resistant LVFA (Fig. 7). Similar results
were obtained with apormorphine (a dopamine
agonist), clonidine (a NA agonist), and amphetamine
(an indirect agonist of both dopamine and NA).
Administering these compounds (alone or in various
combinations) to rats following pretreatment with
reserpine and atropine results in pronounced behav-
ioral hyperactivity accompanied by continuous large
amplitude slow wave activity in the neocortex. This
finding, together with the negative results of selective
interference with catecholamines (summarized in the
preceding paragraph) indicates that the catechol-
amines are neither necessary nor sufficient for the
production of atropine-resistant LVFA in the neocor-
tex.
RESERPINE
CTX + RO4-4602 + 1-D0PA
5.0 sec
• ATROPINE
Figure 7. Effects of reserpine, 1-dopa, and atropine on
neocortical electrical activity and behavior. CTX: neocortex;
MVMNT: movement sensor output. Top traces: After treat-
ment with reserpine (10 mg/kg/day x 2). Note: 1, low
voltage fast activity (LVFA) during immobility; 2, LVFA
during spontaneous movement; 3, irregular slow waves
during immobility; 4, rhythmic spindle activity during
immobility. Middle traces: 60 min after injection of Ro-
4-4602 (50 mg/kg) and 30 min after 1-dopa (300 mg/kg),
LVFA is nearly continuous. The rat moves its head, rears, and
walks. Bottom traces: 10 min after injection of atropine (50
mg/kg), all LVFA is abolished although rat is very active,
walking and gnawing at the apparatus. (From Vanderwolf et
al. 1980; reprinted with permission of Elsevier/North-
Holland Biomedical Press.)
470 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
Quite different results were obtained when
(8-phenylethylamine was administered following pre-
treatment with reserpine and atropine (Fig. 8). Within
2-5 min after injection of this compound good LVFA
appeared, together with a behavioral syndrome of head
movements and stepping. These behavioral effects are
probably due to a release of residual dopamine (Fuxe,
Grobecker & Jonsson 1967), which is only partially
eliminated by the reserpine pretreatment. The appear-
ance of the atropine-resistant LVFA does not appear to
depend on the presence of dopamine. Rats treated with
a combination of reserpine and a-methyl-p-tyrosine
retain virtually no dopamine. Consequently they
display little or no motor activity when /3-phenyleth-
ylamine is injected, but atropine-resistant LVFA is
undiminished. Therefore, it appears that /3-phenyl-
ethylamine is capable of restoring atropine-resistant
LVFA and that this restoration does not depend on the
presence of catecholamines.
It is unlikely that restoration of atropine-resistant
LVFA in reserpinized rats by /3-phenylethylamine is
due to a direct effect on catecholaminergic receptors.
RESERPINE + ATROPINE
t fl-PHENYLETHYLAMINE
. ^ ^ ^
f
Figure 8. Effect of /3-phenylethylamine (80 mg/kg) on
neocortical electrical activity in a rat pretreated with reser-
pine (10 mg/kg) and atropine (50 mg/kg). Abbreviations as in
Fig. 4 except that L and R refer to left and right parietal
cortex. Top traces: 16 hr after reserpine injection and 0.5 hr
after atropine. At times marked "p," rat is induced to struggle
by being picked up. LVFA is absent. Lower traces: Nine min
after injection of phenylethylamine (PEA) nearly continuous
LVFA is present together with spontaneous stepping move-
ments of the forelimbs. (From Vanderwolf et al. 1980;
reprinted with permission of Elsevier/North-Holland Bio-
medical Press.)
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
First, the effects of /3-phenylethylamine are distinctly
different from the effects of direct-acting catechol-
aminergic agonists such as dopamine (introduced via
1-dopa), apomorphine, or clonidine. Second, the effec-
tiveness of /3-phenylethylamine was not abolished by
blocking dopamine and norepinephrine receptors with
chlorpromazine, propranolol, or trifluoperazine.
Therefore, it is likely that /3-phenylethylamine
produces atropine-resistant LVFA in reserpinized rats
through an interaction with an unknown type of
monoamine receptor which is distinct from the norepi-
nephrine and dopamine receptors. The nature of this
receptor and the identity of its ligand under normal
conditions remain problems for future research. For
various reasons, it need not be assumed that /3-phenyl-
ethylamine is normally a transmitter or modulator in
an aminergic reticulo-cortical pathway, although this is
a possibility. /3-Phenylethylamine is not depleted by
reserpine, at least not in the hypothalamus (Boulton,
Juorio, Philips, & Wu 1977) while the compound
essential to atropine-resistant LVFA is depleted (or
otherwise inactivated) by reserpine. Furthermore, /3-
phenylethylamine, unlike acetylcholine or norepineph-
rine, is not readily released from rat neocortex by
electrical stimulation (Saldate & Orrego 1978). There-
fore, /3-phenylethylamine may be a direct or indirect
agonist of an unknown trace amine which normally
plays an essential role in the production of atropine-
resistant LVFA.
Although catecholamines do not play an essential
role in cortical activation, they may act indirectly by
somehow exerting an excitatory influence on: (a) cho-
linergic neurons presumably responsible for atropine-
sensitive LVFA, and (b) trace-aminergic neurons
which may be responsible for atropine-resistant LVFA.
Such influences are suggested by a number of different
phenomena.
1. Motionless rats treated with large doses of reser-
pine or dopamine receptor blockers such as phenothi-
azines tend to display less LVFA than undrugged
motionless waking rats. It may be hypothesized that
cholinergic corticopetal neurons receive a reduced
excitatory input under these circumstances, a sugges-
tion consistent with the decreased release of acetylcho-
line from the neocortex following treatment with
chlorpromazine (Phillis & Jhamandas 1971) and with
the increased acetylcholine content of the brain in
reserpinized animals (Hrdina & Ling 1973; Malhotra &
Pundlik 1959). Increased acetylcholine content is
usually correlated with decreased release (Szerb, Malik
& Hunter 1970).
2. The finding that dopamine agonists (1-dopa,
amphetamine, apomorphine, and bromocriptine) all
increase the release of acetylcholine from the neocortex
may be due to increased excitation of corticopetal
cholinergic neurons by a dopaminergic mechanism
(Pepeu & Bartolini 1968; Pepeu, Mantovani & Pedata
1978). This explanation could also account for the fact
that the LVFA produced by dopamine agonists (1-
dopa, amphetamine, apomorphine, LSD-25) in reser-
pinized rats is sensitive to atropine (Vanderwolf,
Robinson & Pappas 1980). The increased LVFA
following 1-dopa treatment in cats (Jouvet 1967) may
also result from dopaminergic activation of cholinergic
corticopetal neurons.
3. In normal rats, unlike those pretreated with reser-
pine, the LVFA produced by amphetamine is resistant
to atropine (Vanderwolf 1975; Schallert, De Ryck &
Teitelbaum 1980). This might be due to trace-aminer-
gic neurons, excited by catecholamine release, produc-
ing LVFA in the neocortex. Alternatively, trace amines
may be released by amphetamine directly, without the
mediation of dopamine.
4. It has been reported that dopaminergic blocking
drugs, such as phenothiazines, potentiate the slow-
wave-producing effects of atropine (Bradley & Hance
1957). Such potentiation can probably be understood in
terms of the behavioral effects of these drugs (Vander-
wolf 1975). Atropine produces a behavioral syndrome
of hyperactivity in rats, consisting of head movements,
stepping, and forward locomotion. Such behaviors are
accompanied by atropine-resistant LVFA. Doparnine-
blocking drugs, such as phenothiazines, reduce both the
hyperactivity and the occurrence of atropine-resistant
LVFA, but the remaining spontaneous motor activity
remains strongly correlated with the occurrence of the
LVFA. d-Amphetamine intensifies atropine-induced
hyperactivity, resulting in continuous movement
accompanied by continuous LVFA (Vanderwolf 1975;
Schallert, De Ryck & Teitelbaum 1980). These effects
of amphetamine and dopamine-blocking drugs suggest
that dopaminergic mechanisms control both the occur-
rence of spontaneous motor activity and the correlated
occurrence of atropine-resistant LVFA. It is even possi-
ble that dopaminergic mechanisms play a role in the
normal correlation between atropine-resistant LVFA
and Type 1 motor activity. This is suggested by the
observation that rats treated with a combination of
a-methyl-p-tyrosine and reserpine (virtually eliminat-
ing brain dopamine) display good atropine-resistant
LVFA in the absence of significant motor activity
following the administration of /3-phenylethylamine.
Presumably, /3-phenylethylamine stimulates the atro-
pine-resistant pathway directly, but in the absence of
dopamine, Type 1 motor activity cannot occur.
Reticulo-cortical activity during sleep
Thus far we have discussed primarily the relations of
electrocortical activity to behavior during the waking
state. However, slow wave recording techniques are
also used extensively as an index of reticulo-cortical
activity during sleep. In the light of the behavioral and
neuropharmacological correlates of reticulo-cortical
activity during waking which we have presented
above, an obvious question is whether or "not these
correlations generalize to reticulo-cortical activity
during sleep. In the following paragraphs we attempt
to answer this question.
a) Quiet (slow wave; synchronized) sleep. Prior to
sleeping most animals seek out a quiet protected loca-
tion, assume a characteristic "sleep posture," and,
having adopted this posture, remain relatively immo-
bile. During this period of immobility large slow waves
gradually appear in the neocortical EEG record. The
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 471
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
hippocampal record is characterized by LIA. It must
be emphasized that the occurence of hippocampal LIA
and neocortical large amplitude slow waves during the
immobile phase of sleep is not unique to sleep since
similar wave patterns occur during immobility in the
waking state as well (see above). A waking atropinized
rat, like the rat in quiet sleep, displays continuous large
slow waves during immobility. The latter observation
suggests that perhaps an atropine-sensitive (presum-
ably cholinergic) reticulo-cortical input, which is capa-
ble of producing LVFA during immobility, is inactive
during quiet sleep. This suggestion is supported by
reports that ACh release from the neocortical surface is
reduced during quiet sleep, relative to the release seen
during waking or active sleep accompanied by LVFA
(Celesia & Jasper 1966; Jasper & Tessier 1971).
Periodically animals move (i.e., shift posture) during
quiet sleep. Such postural shifts are invariably accom-
panied by the appearance of neocortical LVFA and
hippocampal RSA (Glotzbach 1975). This occurs even
though the animal may not open its eyes, lift its head,
or show any other signs of behavioral "arousal." The
research on waking animals reviewed above would
suggest that this movement-related LVFA and RSA
accompanying postural shifts during quiet sleep is due
to activation of noncholinergic reticulo-cortical path-
ways. At present there is no direct evidence to support
this contention.
b) Active (paradoxical, desynchronized, rapid eye
movement) sleep. At a behavioral level, active sleep is
characterized by a tonic reduction in muscle tonus
interrupted periodically by bursts of phasic activity in
virtually all the somatic muscles, including the extra-
ocular muscles (thus producing rapid eye movements,
REM). Work by Pompeiano and others (Chase 1974;
Pompeiano 1967) has revealed that the reduction in
muscle tonus results from a postsynaptic inhibition of
alpha and gamma spinal motor neurones as well as a
phasic presynaptic inhibition of la spinal sensory affer-
ents. The phasic bursts of muscular twitches appear to
result from activity in descending systems including
the pyramidal tract, rubrospinal tract, and reticulospi-
nal fibres (Pompeiano 1967; Siegel 1979a; 1979b;
Vertes 1979). Since the spinal motor neurones and
reflex afferents are strongly inhibited, the muscular
activity which results from these descending discharges
is slight in comparison with that occurring during
waking behavior. However, the pattern of impulses
descending from the brain during the phasic episodes
of active sleep is probably similar to the pattern
occuring during some active waking behaviors. Siegel
(1979a; 1979b) has summarized data showing that the
firing patterns of many reticular formation neurones is
similar during waking movement and the phasic events
of active sleep (see also below).
Ascending brainstem influences fluctuate in relation
to the phasic descending influences or peripheral
phenomena of active sleep. Increases in the frequency
of ponto-geniculo-occipital (PGO) spikes, for example,
are correlated with other phasic events in active sleep.
Since similar PGO spikes occur in response to a variety
of novel stimuli in waking cats, Bowker & Morrison
472 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
(1977) suggest that the spikes occur in active sleep as
responses to spontaneously generated "sensory" stim-
uli. Phasic phenomena also occur in hippocampal and
neocortical slow wave activity, presumably in response
to ascending reticular volleys. During the intervals
between phasic episodes, hippocampal RSA has a
frequency of about 6 Hz but the frequency rises to 8
Hz or more during bursts of muscular activity (Robin-
son, Kramis & Vanderwolf 1977; Soulairac, Gottesman
& Thangapregassam 1965; Whishaw & Vanderwolf
1973). Hippocampal "theta cells" which selectively
increase their firing rate during Type 1 behaviors in
the waking state also increase their firing rate during
active sleep (Rank 1973; 1975).
It appears possible to obtain active sleep in heavily
atropinized rats provided that they have been deprived
of active sleep for several days. In such rats the 6 Hz
RSA, which is normally present in the intervals
between the phasic episodes of active sleep, is abol-
ished. However, the higher frequency RSA which
normally accompanies the phasic muscular twitches of
active sleep is well preserved (Robinson et al. 1977;
Usui & Iwahara 1977). Furthermore, if active sleep-
deprived rats are anesthetized with urethane they
display long trains of 5-6 Hz RSA but do not display
phasic muscular twitches or the higher frequency RSA
normally associated with these twitches. Therefore, it
appears that the RSA occurring during active sleep is
comprise of a 5-6 Hz atropine-sensitive and urethane-
resistant component which can occur during immobil-
ity as well as of a higher frequency component which is
atropine-resistant, urethane-sensitive, and occurs in
relation to phasic muscular activity. These data suggest
that: (1) a (presumed) cholinergic input which
produces RSA is tonically active during active sleep,
and (2) the presumed noncholinergic input which
produces higher-frequency RSA correlated with Type
1 behavior in the waking state is phasically active in
association with the muscular twitches of active sleep.
During active sleep in atropinized rats neocortical
activity consists of: (a) short periods of LVFA asso-
ciated with the phasic bursts of muscular activity, and
(b) periods of large amplitude irregular slow waves
during the quiescent intervals. Undrugged rats tend to
display continuous LVFA throughout an entire episode
of active sleep (although 6-9 Hz rhythmic spindle
activity occasionally occurs during immobile periods
between the bursts of phasic muscle activity, just as in
the waking motionless rat). Therefore, during active
sleep the neocortex, like the hippocampus, may receive
both a tonic cholinergic input and a phasic noncholin-
ergic input correlated with phasic motor activity (Rob-
inson et al. 1977).
The foregoing data suggest that the mechanisms
which produce hippocampal RSA and neocortical
LVFA in the waking state also produce these wave
patterns during active sleep. However, Monmaur,
Houcine & Delacour (1979) have recently reported
that posterior septal lesions abolish the RSA which
usually accompanies waking behaviors without sup-
pressing the RSA associated with active sleep. Lesions
located more anteriorly in the septum, and in the
region of the diagonal band of Broca, abolish the RSA
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
associated with active sleep, but not that associated
witli waking behaviors. While these experiments are
not incompatible with the idea that the same neuro-
chemical systems produce RSA during waking and
active sleep, they do suggest that different neuroana-
tomical systems may underlie hippocampal activation
in these two different states.
In general, it is probably that brain activity and
patterns of motor output during active sleep are quite
similar to the patterns that occur during waking (with
the exception that environmental stimulus control of
these patterns is largely absent during active sleep).
This is suggested by studies of active sleep in cats
following chronic lesions of the pons, which appear to
abolish the muscular atonia characteristic of normal
active sleep. In such cats, active sleep episodes take the
form of dramatic displays of motor activity which
resemble such waking behaviors as exploration, attack,
or the capture of prey (Jouvet & Delorme 1965; Henley
& Morrison 1974; llendricks, Morrison & Mann 1980;
Sastre & Jouvet 1977). Despite this vigorous motor
activity, the cats appear to be "asleep," since they are
unresponsive to visual stimuli, their nictitating
membranes are relaxed and their pupils are miotic.
Furthermore, the motor displays are easily interrupted
by auditory stimuli which awaken the cats.
Since the phasic motor components of active sleep
are generally accompanied by atropine-resistant hippo-
campal RSA in normal rats, one might expect that the
motor activities released following locus coeruleus
lesions would consist largely or entirely of Type 1
behavior. This question has not yet been examined in
rats, but llendricks, Bowker & Morrison (1977) report
that in cats with locus coeruleus area lesions, the motor
displays of active sleep resemble "orienting, searching,
stalking, rage, and attack." Behaviors resembling "eat-
ing, drinking, grooming, urinating, defecating, or
reproductive behavior" were not observed. However,
Sastre & Jouvet (1977) did observe grooming behavior
during active sleep in cats with locus coeruleus lesions.
Although more detailed descriptions would be desir-
able, it does appear that Type 2 behavior is relatively
rare in these preparations during active sleep, while
Type 1 behavior is common.
A question which arises from the foregoing experi-
ments is: Which transmitter system(s) is (are) responsi-
ble for producing neocortical LVFA and hippocampal
RSA during the periods of phasic motor activity of
active sleep? Jouvet (1972; 1974) has suggested that NA
has an important role in the generation of LVFA in
both active sleep and the waking state. The experi-
ments discussed above (in the section called "Neocorti-
cal activation and behavior: Monoaminergic in-
fluences") have led us to conclude that NA is not
critical for the production of LVFA during waking. On
the basis of other evidence, other authors have
concluded that NA is not critical for the production of
LVFA during active sleep either (Jacobs & Jones 1978;
Jones ft al. 1977; Ramm 1979). It is possible, however,
that a trace amine is essential for the generation of
LVFA during active sleep; the experiments necessary
to examine this hypothesis have not yet been carried
out, however.
A new synthesis
In the past 30 years there has been almost unanimous
agreement among neuroscientists that the projections
from the brainstem reticular formation to the cerebral
cortex play an essential role in sleep and waking
behavior and in the psychological phenomena of
consciousness, vigilance, awareness, alertness, atten-
tion, and arousal. We have reviewed evidence that this
view is fundamentally unsound. The ascending reticu-
lo-cortical pathways whose activity results in neocorti-
cal LVFA and hippocampal RSA appear to consist of at
least two distinct subsystems. The normal activities of
these subsystems are related to behavior in different
ways but neither of them appears to correlate with
behavior in the way suggested by the classical concepts
of arousal, vigilance, or consciousness. What theoretical
approach can we now offer to replace the venerable
reticulo-cortical arousal theory?
A good place to begin is to consider the behavior of
totally decorticate animals in which all reticulo-cortical
effects are necessarily abolished. A striking feature of
decorticate or even decerebrate rats (Berntson & Micco
1976; Grill & Norgren 1977; Vanderwolf, Kolb &
Cooley 1978; Woods 1964) and of decorticate cats
(Bard & Rioch 1937) is the quality of preservation of
the many distinctive motor patterns normally observed
in these species. Totally decorticate rats sniff or nibble
at proffered objects, walk, jump, and sit up to wash
their faces in a normal or near-normal manner. They
also sleep, often while lying in a curled-up posture, as
normal rats frequently do. Auditory or tactile stimuli
applied during sleep elicit an arousal or awakening
reaction consisting of raising the head, opening the
eyes, and the assumption of a standing position. Simi-
larly, decorticate and destriate (thalamic) or decere-
brate cats display at various times the postures and
ocular activity characteristic of quiet sleep, active
sleep, and the waking state, although there are quanti-
tative changes in the proportion of the day spent in
these different states (Villablanca 1966; Villablanca &
Marcus 1972). Finally, decorticate rats display a circa-
dian rhythm of spontaneous head movements, walking,
and rearing (Fig. 9). Lesions of the hypothalamus, not
the cerebral cortex, disrupt circadian rhythms (Richter
1967; Rusak & Zucker 1975; Stephan & Zucker 1972).
These results indicate unequivocally that the dience-
phalon, brainstem, cerebellum, and spinal cord contain
the neural networks necessary for the principal behav-
ioral phenomena of quiet sleep, active sleep, awaken-
ing from sleep, and the postures and phasic motor
patterns characteristic of the waking state. Ascending
reticulo-cortical systems do not play an essential role in
the production of these behavioral states. However,
descending reticular projections appear to be of great
importance. The behavior of decorticate or decere-
brate preparations is presumably dependent on reticu-
lospinal projections, which, together with vestibulospi-
nal, rubrospinal, and other descending pathways exert
a powerful control over the activity of spinal motoneu-
rones (Shapovalov 1975). This conclusion is supported
by the fact that the firing of many neurons in the
reticular formation in freely moving animals is strongly
THE BEHAVIORAL AND BRAIN SCIENCES (1981). 4 473
Vanderwolf & Robinson: Reticulo-cortical activity and behavior
% TIME ACTIVE
o o o o o o o
Figure 9. Percentage of time per hour occupied by head movement, walking, and rearing in three totally decorticate rats
during a 3-day period. (From Vanderwolf, Kolb & Cooley 1978).
correlated with motor activity (Siegel 1979a). Destruc-
tion of reticulospinal pathways of the medial brainstem
results in severe behavioral incapacitation (Kuypers
1964).
If the ascending reticulo-cortical pathways are not
directly involved in the basic phenomena of sleep,
arousal, and waking, then what is their function? The
data discussed above indicate that the ascending reticu-
lar activating system comprises at least two functional
components with quite different relations to behavior.
One component, which is probably dependent on cho-
linergic transmission at one or more points, is responsi-
ble for any hippocampal RSA or neocortical LVFA
sh%$Uwhich occurs during behavioral immobility or
simple reflexive or consummatory behavior (Type 2
behavior). This component is also responsible for the
RSA and LVFA occurring during the quiescent inter-
vals of an active sleep episode or during the anesthesia
produced by volatile anesthetics. We refer to this
component as "atropine-sensitive," since atropine has
provided the chief method for investigating it. The
occurrence of atropine-sensitive RSA and LVFA
during the anesthetic state and the inter-twitch inter-
vals of active sleep emphasizes the fact that activity in
the reticulo-cortical pathways producing these wave-
forms is not dependent on the maintenance of muscle
tone or the occurrence of phasic motor activity.
In all species studied so far, atropine-sensitive
neocortical LVFA can be readily elicited by sensory
stimulation, without concurrent elicitation of phasic
motor activity. Atropine-sensitive hippocampal RSA
can be elicited by sensory stimuli in this way in some
species (rabbit, guinea pig) but not in others (rat). The
significance of these species differences, and of the fact
that atropine-sensitive LVFA occurs spontaneously
much more frequently than atropine-sensitive RSA in
all species, is unknown at present.
The fact that atropine-sensitive LVFA and RSA can
often be elicited by sensory stimuli may suggest that
these waveforms reflect the activity of mechanisms
474 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
% TIME ACTIVE % TIME ACTIVE
5888883888
involved in the stimulus control of behavior. Behavioral
investigations have revealed a number of different
mechanisms, such as elicitation (release), guidance, and
reinforcement, by which environmental stimuli control
animal behavior (Eibl-Eibesfeldt 1970; Hinde 1970;
Skinner 1938; 1969; 1974). Interoceptive and proprio-
ceptive stimuli also affect behavior. Animals or humans
who are demented, psychotic, or intoxicated may be
said to display impaired stimulus control of behavior
when they react inappropriately to environmental
signals. It may be that brain cholinergic systems,
including the atropine-sensitive ascending reticular
activating system, play an essential role in normal
responses to environmental situations. These hypoth-
eses are supported by recent evidence that brain cho-
linergic systems are selectively impaired in senile
dementia. Choline acetyl transferase and acetylcholin-
esterase activity is very low in the neocortex, hippo-
campus, and striatum of senile demented patients (Alz-
heimer's disease) but other brain enzymes appear to be
well preserved (Davies & Maloney 1976; Perry, Perry,
Blessed & Tomlinson 1977; Perry, Perry, Gibson,
Blessed & Tomlinson 1977; Perry, Tomlinson, Blessed,
Bergman, Gibson & Perry 1978; Reisine, Yamamura,
Bird, Spokes & Enna 1978). In normal humans and
aged experimental animals, treatment with choline or
cholinergic agonists has been reported to improve
performance in learning tasks (Bartus, Dean, Goas &
Lippa 1980; Davis, Mohs, Tinklenberg, Pfefferbaum,
Hollister & Kopell 1978; Sitaram, Weingartner & Gillin
1978). Interference with central cholinergic function
due to a choline deficient diet (Bartus et al. 1980) or
central muscarinic blocking drugs, disrupts both
learned and spontaneous (untrained) behavior (see
reviews by Brimblecombe 1974; Hunter, Zornetzer,
Jarvik & McGaugh 1977; Longo 1966). These data are
consistent with the hypothesis that cholinergic reticulo-
cortical fibres play a role in normal stimulus control of
behavior. At present, however, it is not possible to
exclude a role for other central cholinergic systems as
 Vanderwolf & Robinson: Reticulo-cortical activity and behavior
well.
An important conclusion of this review is that there
is a second component of the ascending reticular acti-
vating system which is noncholinergic and is resistant
to large doses of atropine. This component produces
hippocampal RSA and neocortical LVFA if, and only
if, voluntary behaviors such as locomotion or head
turning (Type 1 behavior) are being performed or if
muscular twitches are occurring during an episode of
active sleep. The effect of this input is not obvious in
the spontaneous electrical activity of the neocortex in a
normal animal but it becomes very clear following
treatment with atropine. Presumably, atropine un-
masks the effect of a noncholinergic input by eliminat-
ing concurrent cholinergic inputs. Atropine-resistant
hippocampal RSA and neocortical LVFA are abolished
by volatile anesthetics and morphine and the produc-
tion of atropine-resistant LVFA appears to be depen-
dent on the presence of a trace amine.
There has not yet been an intensive study of the
brainstem origin of reticulohippocampal and reticulo-
neocortical pathways whose activity is correlated with
Type I behavior. Stimulation experiments suggest that
this origin is rather diffuse (Robinson & Vanderwolf
1978). Vertes (1979) has made an important finding in
this field by demonstrating the existence of pontine
neurons which fire in relation to Type 1 behavior and
the phasic events of active sleep. These neurons may
activate the hippocampus, as Vertes suggests, but may
also activate the neocortex.
Considering the nature of their relation to behavior,
it seems possible that atropine-resistant reticulo-cortical
inputs may play a role in the control of Type 1
behavior, but have no direct role in Type 2 behavior.
Unfortunately, there are, as yet, no clear behavioral
criteria by which Type 1 or Type 2 behavior can be
classified. In general, Type 2 behavior includes alert
immobility and various reflexive or consummatory
behaviors, while Type 1 behavior includes walking,
manipulation, and other actions of a type which might
be called "voluntary" or "purposive" (Fig. 2). It is
interesting that most Type 1 behaviors are readily
shaped by operant conditioning procedures while a
number of Type 2 behaviors are resistant to such
shaping (Amiable & Weardon 1979; Shettlevvorth
1975). However, no detailed analysis of possible rela-
tions between ease of operant conditioning and the
electrocortical correlates of behavior has yet been
attempted.
Another possible distinction between Type 1 and
Type 2 behavior is that Type 1 behaviors usually
involve movement from one place to another while
Type 2 behaviors are performed in a single place
(O'Keefe & Nadel 1978). [See also BBS multiple book
review of O'Keefe & Nadel 1978 in BBS 2(4) 1979.]
While this distinction often does apply, there seem to
be some Type 1 movements such as head scans (Schal-
lert et al. 1980) which are accompanied by atropine-
resistant RSA and LVFA even though they do not
involve movement from one place to place in the sense
intended by O'Keefe & Nadel. It may be that no single
denning behavioral characteristic of Type 1 behavior
will ever be found. Type 1 behaviors may be character-
ized only by being normally subject to control by
complex cerebral systems which are not directly
involved in the control of simpler reflexive and
consummatory behavior. Analysis of these cerebral
control systems is a problem for future research. The
possible physiological role of a diffuse trace amine-
dependent input to the neocortex, for example,
remains unknown.
In this connection, is is of interest that trace amine
activity appears to be abnormal in paranoid schizo-
phrenia and depression (Potkin, Karoum, Chuang,
Cannon-Spoor, Phillips & Wyatt 1979; Sandier, Ruth-
ven, Goodwin & Coppen 1979). Thus, it is conceivable
that malfunction of an ascending trace amine-depen-
dent reticulo-cortical system is involved in some
psychiatric disorders.
A neglected approach to reticulo-cortical function in
relation to behavior is provided by the study of decorti-
cate animals. Decortication produces a profound disor-
ganization of behavior, affecting both specially trained
("learned") behavior and behaviors which are
frequently regarded as "innate" or "unlearned,"
including feeding, food hoarding, nest building,
mating, grooming, and general social behavior (Lash-
ley 1929; 1935; Vanderwolf et al. 1978). Decorticate
animals appear to retain most of the motor components
of normal adaptive behavior but fail to display these
components at the correct times and places. For exam-
ple, a normal rat will pick up and carry home (hoard)
food pellets that are lying about in the open. A decorti-
cate rat never does this, even though it is perfectly
capable of picking up food in its mouth and runs about
very actively.
We suggest that the cerebral cortex is involved in
behavior control systems which, in normal animals,
determine the occasions on which particular motor
patterns are to be displayed. The behavior of decorti-
cate animals suggests that subcortical mechanisms are
largely capable of generating the "motor score" (Weiss
1941) characteristic of a given behavior pattern such as
walking or rearing, but that the cortex plays a major
role in determining when walking or rearing should be
performed. The activity of the cortex, in turn, is
influenced by specific sensory input and by reticulo-
cortical inputs. Output from the cortex may exert a
descending control over posture and movement
(behavior) largely by way of reticulospinal, rubrospi-
nal, and other descending pathways which originate in
the brainstem. Numerous corticosubcortical anatomi-
cal connections suggest the possibility of this type of
control (see Knook 1965 for extensive references).
The effects of cortical damage on behavior are
frequently interpreted in terms of a loss of the projec-
tion areas of specific sensory systems. While such loss is
undoubtedly a major factor, a part of the behavioral
deficit may result from interruption of diffusely
projecting reticulo-cortical pathways. Many years ago,
Lashley (1929) suggested that the cerebral cortex had
some general function in behavior distinct from the
analysis of specific sensory input or the organization of
specific motor output, but he did not specify the
anatomical basis of this general function. Perhaps the
nonspecific pathways from the brain stem to the
THE BEHAVIORAL AND BRAIN SCIENCES (1981). 4 475
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
neocortex are the basis of the general function hypo-
thesized by Lashley. The diffuse nature of these path-
ways might account for Lashley's finding that large
lesions at any location in the cerebrum produce a
general deterioration in behavior.
The specific roles of Ach-dependent and trace
amine-dependent reticulo-cortical pathways in the
overall organization of brain activity and behavior is a
topic for future research. We believe that this review
has shown that careful descriptive studies of behavior
are likely to play an important role in such research.
ACKNOWLEDGMENT
Preparation of this paper was supported by a grant (AO-118)
from the Natural Sciences and Engineering Research Council
of Canada.
Open Peer Commentary
Commentaries submitted by the qualified professional readership
of this journal will be considered for publication in a later issue as
Continuing Commentary on this article.
Is a behaviorist's approach sufficient for
understanding the brain?
Thomas L. Bennett
Department of Psychology, Colorado State University, Fort Collins, Co.
80523
Vanderwolf & Robinson's (V&R) presentation is essentially
composed of two articles. The first describes the neurophysi-
ology of reticular, neocortical, and hippocampal electrical
activity while the second attempts to relate patterns of
electrical activity to behavior. I have no major quarrels with
the first, but I am uncomfortable with the second, largely
because I believe that the authors have been unnecessarily
restrictive in their behavioral analysis.
The classical arousal theory of reticulo-cortical activity has
its problems, as V&R point out. However, a feature of this
view is that it is couched in cognitive terms such as attention,
arousal level, alertness, and consciousness. How can one assess
the validity of this theory for describing the electrophysiologi-
cal correlates of these processes when one rejects such
concepts (as the authors do) and refuses to include them in a
behavioral analysis of neurophysiological events?
I think it would be more accurate to view this paper as a
behaviorist's view of the behavioral correlates of reticulo-
cortical activity than as a resynthesis of the theory. V&R's
approach is to look only at body movements when they
investigate behavior, following the tradition of behaviorism in
the footsteps of Watson and Skinner. The behaviorist view of
psychological processes, in which the legitimate subject of
behavioral analysis is restricted to overt movements, was an
important stage in the history of experimental psychology
(and especially the psychology of learning), enabling it to
"get its feet on firm ground ' during its infancy. Applied to
physiological psychology, this approach proved invaluable for
the early development of that discipline as well. But experi-
mental psychology and physiological psychology are no
476 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
longer in their infancy, and cognitive processes such as
attention, perception, and consciousness are today considered
to be just as legitimate for study as were overt movements for
the behaviorists many years ago.
V&R apparently do not share this view. In studying EEG
correlates of behavior they state that "behavior was described
in terms of movement and posture, and inferential terms such
as perception, attention, arousal, motivation, memory, and so
on, were deliberately avoided in describing the behavior of
the animals." I take issue with this approach because I believe
this behavioral analysis to be unnecessarily restrictive at the
stage we have now reached in the development of our
discipline. In addition, such an approach leads to an investiga-
tor's possibly missing a wealth of information.
In the case of hippocampal EEG correlates of behavior, the
behaviorist approach resulted in Vanderwolf and his
colleagues' concluding that hippocampal slow-wave activity
is a correlate of so-called "voluntary " movements. (But is
making a distinction between voluntary versus involuntary or
automatic behaviors not inferential?) Many neuroscientists
believe that Vanderwolf and his colleagues, in rejecting
attention, perception, and memory processes, came to errone-
ous conclusions regarding the significance of hippocampal
slow-wave activity. Instead, these investigators suggest that
the appearance of this biorythm is specifically related to the
cognitive processes which Vanderwolf rejects (see, for exam-
ple, Adey 1966; Bennett 1975, 1979; Grastyan, Karmos,
Vereczkey & Kellenyi 1966; Isaacson 1974; Kemp & Kaada
1975). Interestingly, Grastyan originally thought that hippo-
campal slow-wave activity was a correlate of voluntary move-
ment; but further observations, in which he had not made the
a priori decision to reject inferred behavioral processes from
his analysis (as Vanderwolf and his colleagues have), led
Grastyan to reject his speculation as premature and incorrect
(personal communication). Those original observations were
never published, and we instead attribute to him the view
that hippocampal slow-wave activity is a correlate of an alert
animal; attending to and processing information about a
potentially significant environmental stimulus - a hypothesis
which a number of us have heartily endorsed.
Actually, it now appears that there are two bandwidths of
hippocampal slow-wave activity, with different behavioral
correlates: a slower, 4-7 Hz, pattern (theta activity) that is a
correlate of cognitive processes and is blocked by anticholin-
ergic agents such as atropine and scopolamine, and a faster,
8-12 Hz, rhythmic activity which is more closely related to
the execution of voluntary movement and is not blocked by
anticholinergic agents. Please note that this faster activity is
not theta (it falls in the range of alpha), despite the popularity
of denoting it as such (for example, see V&R's Figure 2).
Nevertheless, the point to be made is that rejecting inferred
behavioral processes from an analysis of the functions
performed by the brain in regulating behavior needlessly
restricts the wealth of information that can be gleaned from
such inquiries; indeed, such an approach may produce erro-
neous conclusions. At the very least, such narrow investiga-
tions should be prefaced by a statement that they are thus
limited and followed by the conclusion that the obtained
results have no relevance to describing the functions of the
brain in higher behavioral processes; rather, such inquiries
only describe the brain's functions in overt motor operations.
Unfortunately, the behaviorist philosophy leads to rather
narrow conclusions when these constraints are in effect.
Consider V&R's major conclusion that "the cerebral cortex is
involved in behavior control systems which, in normal
animals, determine the occasions in which particular motor
patterns are to be displayed." This is an extremely narrow
view of the contributions to behavior made by the cortex,
even in the case of the rat whose cortical mantle is very poorly
 Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
developed. Even the lowly rat has been a rich source of
information for experiments conducted in the field of cogni-
tive psychology. Physiological psychology no longer needs to
confine itself to simple descriptive analyses of overt behavior.
As a discipline, it is reaching maturity and can make many
well-substantiated statements about how the brain regulates
complex behavioral processes.
Behavioral problems related to the
interpretation of brain rhythms
Gydrgy Buzsaki,*' Robert L. Isaacson," and John H.
Hannigan, Jr.b
'Physiology Institute, Medical School. University of Pecs, Pecs, Hungary
and "Department of Psychology and Center of Neurobehavioral Sciences,
State University of New York at Binghamton, Binghamton, N, Y. 13901
The basis of the approach which has been used so extensively
by Vanderwolf, Robinson, and their associates is the associa-
tion of certain behaviors with electrical activities recorded
from the hippocampus and neocortex. Essential to this under-
taking is the identification of the behavioral units with which
correlations are to be made. The authors of the target article
say that their aim is to study behaviors in terms of postures
and movements which they believe would be in accord with
both behavioristic (i.e., Skinnerian) and ethological
approaches. Frankly, we doubt that the behavioral approach
used by Vanderwolf & Robinson (V&R) are appropriate to
either. We do not think V&R's behavioral units are Skinner-
ian, since some of the more-or-less explicit categorizations are
made on bases other than purely behavioral ones ("manipula-
tion" of objects), and because of the use of the notion that
some behaviors are "voluntary." More important, however, is
our view that V&R's approach is not ethological. Ethologists
have rejected extreme behavioristic approaches and look for
units of behavior which are meaningful patterns in the lives
of animals. Many of these units consist of complex patterns of
movements and postures that cannot be isolated from the
settings which make them meaningful. Examined from an
ethological perspective, there is, for example, a great differ-
ence between a foreleg movement in stepping toward a
receptive female and a similar movement made in getting
away from a predator. [See also Johnston: "Contrasting
Approaches to a Theory of Learning" BBS 4(1) 1981.]
Part of the problem is probably due to the methods
commonly used, namely observation of animals in an open
environment. This could account for the relative paucity of
behaviors categorized as type I or type II (e.g., V&R's Figure
2). The small number of behaviors categorized by the authors'
procedures is apparent. The method of simple observation in
a free environment may also account for the fact that hardly
any changes are observed in fundamental movements and
postures after extensive or total neocortical destruction. A
more refined analysis could reveal such changes. For exam-
ple, we have found increases in the frequency and average
duration of grooming bouts, as well as altered rates of
habituation of grooming after even small amounts of neocor-
tical damage in rats. These changes are subtle but consistent
(Reinstein, Hannigan, & Isaacson 1981).
In addition, V&R's arbitrary categorization of behaviors
restricts measurable correlates of both movement and
nonmovement. Careful analysis of the rhythmic electrical
activity in the brain associated with physiological changes
remains an appropriate procedure. Considering such vari-
ables as only a "domain" of inference about "psychological
processes," an opportunity to meaningfully distinguish simi-
lar overt behaviors in terms of EEG may be missed. We
believe that valuable information could be obtained by relat-
ing physiological indexes of internal conditions to electrical
rhythms of the brain and using them as another basis for
making inferences about psychological processes. Further-
more, we suggest that a commitment to an extreme operant
approach to finding electrical correlates of behavior will be
self-defeating in connection with atropine-sensitive activity.
These are thought to occur without movement or behavior,
and consequently there will be nothing with which to corre-
late the electrical activities.
In our opinion, a more powerful approach is to test animals
in situations in which things are required of them. Situations
can be arranged in which ethologically significant behaviors
are obtained and can be analyzed for relationships with the
electrical rhythms of the brain. Through the use of such
paradigms, electrical patterns which occur before meaningful
and specific patterns of behavior can be investigated. Buzsaki,
Grastyan, Tveritskaya & Czopf (1979), and Buzsaki, Hauben-
reiser, Grastyan, Czopf & Kellanyi (1981) have found that
signal-elicited behaviors are accompanied by greater amounts
of rhythmic slow activity in the theta range than is found in
US (unconditional stimulus)-directed "voluntary" behaviors
in both the rat and the cat. The conditioned theta activity
occurring in the absence of locomotion was found to have
high modal frequency peaks (9 Hz in rat, 5 Hz in cat)
indicating it to be of the atropine-resistant type. US-directed
"voluntary" movement was accompanied by lower frequency
rhythmic activities in both species. It was of interest that CS
(conditional stimulus)-elicited head movements were accom-
panied by the higher frequency rhythmic slow activities;
spontaneous head movements were not.
We also believe that serious problems exist for a reticular
formation-hippocampal theory as it relates to "arousal" as
indicated by the rhythmic activities in the hippocampus. The
anatomical question of the actual existence of reticular
formation-hippocampal fibers has not been conclusively
resolved. Neurophysiologically, the almost complete domi-
nance of hippocampal electrical activity by slow-wave activ-
ity has been found after prepontine section in the unanesthe-
tized rabbit (Woodruff, Gage & Isaacson 1973), and after
high mesencephalic transections in the cat (Olmstead &
Villablanca 1977; Radii-Weiss, Zernicki & Michalski 1976),
and the rat (C. Gottesmann, personal communication). The
question of the location of the atropine-sensitive rhythmic
slow-wave generating region still seems obscure.
Finally, we have severe reservations about the pharmaco-
logic evidence marshalled to argue for the involvement of a
"trace amine" (j3-phenylethylamine) in atropine-resistant
neural pathways. It seems unreasonable to postulate a signifi-
cant role for this agent - which can be considered a parent
compound for a host of catecholamine-related compounds -
on the basis of incomplete pharmacologic investigations.
NOTE
* During 1980-1981 at: Division of Neurosurgery, Department of
Surgery, University of Texas, Health Sciences Center, San Antonio,
Texas 78284.
Can the decomposition of attention
clarify some clinical issues?
Enoch Callaway
Department of Psychiatry, University of California, San Francisco, School
of Medicine, San Francisco, Calif. 94143
As William James accurately observed, attention has for each
of us a self-evident and unitary quality. That, it seems, is
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 477
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
Table 1 (Callaway). Dimensions of attention/arousal
Family A Family B
1. Serial Parallel
2. Memory driven Data driven
3. Controlled Automatic
4. Response selection Stimulus evaluation
5. Sustained arousal Phasic arousal
and effort
6. Attention Pre-attentive
7. Cognitive memory Trace memory
Type I (Aminergic) Type II (Cholingeric)
Motor - Operant Sensory - Consumatory
Purposive - Learned Responsive - Reflex
illusion, since attention is being decomposed nowadays into
separable processes. The results of this decomposition seem
confusing, although full of promise. By decomposing electro-
graphic arousal into Type I and Type II, Vanderwolf &
Robinson (V&R) provide an important new addition to the
growing list of dimensions on which arousal/attention can be
pulled apart. Furthermore, this newcomer may help to settle
some of the confusion that exists among the earlier arrivals.
Table 1 gives a partial list of arousal/attention processes. It
is arranged as a sort of a matrix, so that items in each column
share a family resemblance, while each row represents a
dimension that has some empirical justifications. The refer-
ences on the right provide a guide to the details of these
empirical justifications, although the text by Klatzky (1980) is
probably a better practical reference.
No two of these dimensions are the same, yet neither are
they orthogonal. As in family-type classes, each member of a
family has something in common with every other member,
yet is also has something that makes it different from every
other member. For example, parallel and data-driven
processes both seem to operate rapidly, automatically, and
generally outside of consciousness. Nevertheless, some paral-
lel processes can be memory-driven. Consider some of the
classic experiments carried out by Posner (1978) and his
students (McLean & Schulman 1978). First, a prime stimulus
is given as a warning. The prime may be a letter or a nonletter
symbol. Then a pair of target letters is presented and the
subject responds "same" or "different." The response time is
measured. If a subject is taught to evoke an image of a prime
in response to some arbitrarily designated cue, and if a match
between the imagined prime and the targets is unlikely, then
reaction time will be speeded when an actual match occurs,
but will not be slowed if the target is a mismatch. This gain
(speeding with the match) without cost (slowing with the
mismatch) is a classic indication of a parallel system in
operation. Yet the fact that the prime was only imagined
makes it memory-driven.
Before the arrival of Type I and Type II it was difficult to
think of names for the two families that I have labeled A and
B. Family B is generally faster and Id-ish, while A is slow and
Ego-ish. But these are hardly satisfactory definitions. At the
bottom of the Table, I have placed Type I and Type II
electrographic arousals. I believe the situation now becomes
less confusing. Type I is concerned with voluntary behavior
and is response-oriented. It suggests amphetamine-related
benefits such as increased sustained attention and ampheta-
478 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
References
Posner (1978)
Rabbitt (1979)
Shiffrin & Schneider (1977)
Donchin (1979)
Pribram (1977)
Broadbent (1977)
Sutton, Spring & Teuting
(1978)
mine-related toxic effects such as schizophrenic-like psychosis
and response stereotopy. Type I also exerts a direct drive on
Type II since its aminergic activity seems to have an excitory
effect on the cholinergic control of Type II. This suggests the
effects of conscious choice on automatic parallel systems and
the general modulation of automatic motor responses by
controlled attention.
As V&R correctly point out, schizophrenia appears to be a
disease of the Type I systems. A considerable literature
supports the notion that not only is the defect in schizophrenia
confined almost exclusively to the Type I systems, but the
Type II systems remain normal, or even supernormal. This
concept of schizophrenia resolves a number of apparent
paradoxes in the literature on schizophrenic performance.
For example, it is noted that while schizophrenics have
generally slower reaction times, they have faster than normal
alpha-blocking. This would seem to be an example of how, in
schizophrenia, defective functioning of the Type I systems
slows reaction time, while the Type II systems function more
rapidly than normal.
The characteristics of Type II systems remind me of the
sensory distortions and deliria produced by anticholinergic
drugs, and of the general relationship between the cholinergic
system and both mood and pain perception. I am particularly
intrigued by the light this new work sheds on some data that
we collected many years ago (Callaway & Dembo 1958;
Callaway & Band 1958). Based on a wide variety of behav-
ioral experiments it seemed that a sort of narrowed attention
could be induced by a variety of procedures. These proce-
dures included a stimulant (amphetamine), sensory stimula-
tion (cold-presser test), and a strong cholinergic (anticholines-
terase nerve gas). To produce the opposite sort of effect and
broaden attention, the most effective substance seemed to be
atropine. We assumed we were observing classic arousal and
finally stopped pursuing this line of work when subsequent
studies failed to consistently confirm the narrowing effect of
amphetamines. In retrospect, apparently we were inadver-
tantly studying Type II arousal and were thrown off by the
weak tendency of Type I arousal to stimulate Type II arou-
sal.
In conclusion then, I find that the Type I and Type II
distinctions provided by V&R suggest a framework for orga-
nizing some of the various ways that attention/arousal can be
broken into separable processes. I am sure that this synthesis is
too simple, but the Type I/Type II distinctions suggest that
we may be on the verge of making a more reasonable
 Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
organization out of some rather confusing observations, both
from the laboratory and from the clinic.
Is the distinction between Type I and
Type II behaviors related to the
effects of septal lesions?
Neil R. Carlson
Department of Psychology, University of Massachusetts. Amherst, Mass.
01003
At the risk of simplifying matters too much, it might be said
that strategies for research on the neural mechanisms of
behavior can be grouped into two categories: (1) One can
facilitate or interfere with some part or parts of the nervous
system by chemical, surgical, or electrical means and observe
the behavioral phenomena that are altered, or (2) one can
watch the behavior of an animal ("spontaneous" behavior or
behavior elicited by the experimental situation) and see what
chemical or electrical changes may be found in the nervous
system.
An investigator who pursues research that falls under either
of these categories must ask the following question: What is
the best way to categorize the behaviors that are observed?
The level of behavioral analysis has a profound effect on the
kinds of conclusions that can be reached; the conclusions are
constrained, regardless of the results that are finally obtained.
To take a striking example, Delgado (1969) claimed to have
"pacified" a charging bull by telestimulation, while the
apparent truth of the matter was that he simply stopped
attack by stimulating motor systems that caused the animal to
turn, thus aborting its charge (Valenstein 1973). In this case a
behavioral description is clearly superior to one that makes
reference to an inferred process.
The level of behavioral analysis is determined in large part
by the level of the nervous system that one studies. If one
studies the spinal cord, behavioral observations will probably
be made in terms of specific muscle movements. Conversely,
if one is interested in cortical function one generally observes
learning, or attention, or arousal, or other "higher" processes.
The problem is, of course, that these inferred behavioral
phenomena are poorly and inconsistently defined. Vander-
wolf & Robinson (V&R) make the case for an objective
behavioral analysis of reticulo-hippocampal and reticulo-
cortical "arousal."
Most of the time, hippocampal synchrony (theta) and
cortical desynchrony (beta) indicate "arousal," in the sense
that the animal is awake and potentially reactive to stimuli.
Of course, these forms of electrical activity are also recorded
during RKM ("paradoxical") sleep, during which the animal
is presumably reacting to internally generated stimuli,
('diversely, cortical synchrony and hippocampal desynch-
rony indicate (most of the time) that the animal is not
"aroused," and is either asleep or not "attending to" sensory
stimuli. The relation between electrophysiological activity
and the presumed level of arousal has led many investigators
to use the EEC as a measure of activation in an animal that is
unable to perform normal behaviors.
V&R point out that there are many examples of noncorres-
pondence between probable level of "arousal" and the elec-
trical activity of the hippocampus and cortex. Instead of
dismissing these observations as exceptions to a general rule,
the authors assert that one should record specific behaviors
and not attempt to infer the presence of physiological/
behavioral "states." Since the functions of the hippocampus
and neocortex undoubtedly comprise many complex
processes, one is tempted, when studying the electrophysi-
ology of these parts of the brain, to describe the animal's
behavior in terms of inferred complex processes rather than
the specific movements that are being observed. However,
V&R demonstrate that cortical and hippocampal rhythms
correlate much better with particular classes of behavior than
with any internal state that one might reasonably hypothe-
size. In fact, the data they summarize suggest that the concept
of "general arousal," at least as defined electrophysiological-
ly, has little to recommend it.
V&R do an excellent job describing the data that suggest
the existence of two neurochemically distinct reticulo-fugal
systems that are active during Type I ("voluntary") or Type
II ("automatic") behaviors, independent of the animal's puta-
tive state of alertness. I find their analysis especially interest-
ing in light of the results of some studies that my students and
1 have undertaken to determine the functions of the septum.
Until recently, I would have said that most of the behavioral
effects of lesions of the septum could be attributed to an
enhancement of the consequences of reinforcement, caused
by disinhibition of neural mechanisms of reinforcement. This
enhancement would explain many of the phenomena that
constitute the "septal syndrome," such as increased response
rate during performance of an operant behavior, impaired
acquisition of a schedule of reinforcement that requires a low
rate of responding (DRL, or differential reinforcement for
low rate), and more rapid acquisition of alternation tasks,
which may be regarded as discrimination tasks that are cued
by the presence or absence of the reinforcer. (See Fried 1972;
Grossman 1974, 1978; Isaacson 1974 for reviews of the "septal
syndrome.") However, recent (unpublished)*evidence that we
have gathered suggests another interpretation, one which
might be related to the distinction between Type 1 and Type
2 behaviors.
Some classes of behaviors, many of which might be
regarded as species-typical, are impaired or even abolished by
septal lesions. For example, mice with septal lesions do not
hoard, build nests (during pregnancy or lactation, or in
response to cold stress), retrieve their pups, gather string,
climb on the lids of their cages, or run in an activity wheel.
They do kill cockroaches, mate, eat, and drink. They very
readily perform a variety of arbitrary responses (Type 1
behaviors?) when these are reinforced (e.g., they will press a
lever, run through an alley, or poke their head into a hole),
and will sustain a rate of responding far in excess of that of a
normal animal. However, they perform very poorly when a
"species-typical behavior" such as string-pulling or-wheel-
running serves as the operant response. It is as if a class of
behaviors is removed from the animals' repertoire. Even the
behavior of remaining immobile is imparted; mice with septal
lesions do not learn to hold their head still in the poke hole,
although they very quickly learn to poke it in and out,
repeatedly.
The hypothesis that I previously favored - disinhibition of
reinforcement mechanisms - might be replaced by a more
parsimonious one: The unavailability of a class of behaviors
means that the animal spends more time performing the
operant response because it spends less time performing the
various adjunctive behaviors that occur during almost every
schedule of intermitent reinforcement.
The behaviors that survive septal lesions appear to conform
to V&R's description of Type 1 behavior; the animals readily
perform rapid changes in movement or posture. Unfortunate-
ly, the behaviors that are lost do not correspond very well
with Type 2 behaviors, although both might be loosely
characterized as species-typical. The fact that hippocampal
rhythms are controlled by neural systems that travel from the
reticular formation through the septum suggests that V&R's
analysis might provide useful guidance for future research in
this area.
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 479
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
A behaviorist in the neurophysiology lab
Howard Eichenbaum
Department of Biological Sciences, Wellesley College, Wellesley, Mass.
02181
Vanderwolf & Robinson (V&R) and others have added a
great detail to the description of slow wave correlates of overt
behavior. But the new synthesis by V&R is not sufficient to
replace a sophisticated arousal theory of cortical-reticular
relationships. Investigators 30 years ago knew that decortica-
tion does not produce coma, and they knew that neocortical
LVFA occurs during "paradoxical sleep." That is, we have
known for some time that cortico-reticular (as opposed to
more local brainstem) mechanisms in arousal are complex
and subtle. Their understanding will require analyses more
sophisticated than those provided to date.
V&R suggest that such analyses are better served by
detailed behavioral description than by inference to the
underlying psychological phenomena. But their "behavioral
analysis," as such, is unsuccessful, because the described
EEG-behavioral correlates (a) are dissociable and (b) do not
avoid inference to psychological process.
The evidence V&R provide against "traditional" slow-
wave correlates of behavior consists of (1) the exceptions to
their concurrence in subcomponents of normal aroused
behavior and sleep, and (2) the exceptions to disruption of
arousal-sleep patterns following brain damage. Yet V&R's
elegant correlation of behaviors with neocortical LVFA and
hippocampal RSA are also dissociable, in this case by pharma-
cological manipulations. The finding that LVFA can occur in
the brain-damaged, comatose animal convinces V&R that
LVFA is not the proper EEG correlate of arousal. By similar
logic, the finding that atropine eliminates slow-RSA (4-8 Hz)
but not "automatic" behaviors, suggest that "automatic"
behavior is not the proper behavioral correlate of slow-RSA.
Fast-RSA (7-12 Hz) and voluntary movement are more
difficult to dissociate with anesthetics. This may be because
voluntary movement and fast-RSA are causally linked.
(Although anesthetics which affect fast-RSA eliminate both
voluntary and automatic movements.) Curare eliminates
movement and leaves fast-RSA intact. The relevant effect of
curare may in this case be entirely peripheral, but the clear
dissociation of EEG from overt behavior makes obvious the
need for considering internal mechanisms.
Vanderwolf's contrasting of "voluntary" vs. "automatic"
behavior is insightful and appealing, but such terms cannot,
as V&R admit, be described as specific movement patterns,
and they definitely infer the underlying psychological
purposes of behavior. The terms are no less clear than those
they are meant to replace (e.g., "attention"), although they do
introduce a potentially valuable, ethologically relevant
dimension. Nevertheless, it seems unavoidable to use psycho-
logical intermediaries when discussing the hippocampus and
neocortex. The elimination of such terms will come when we
can substitute sufficient mechanistic detail to obviate their
need in explanation.
V&R suggest that we would do better to compare the
details of behavior to EEG, but the success of this strategy
requires a good choice of what to observe, and in how much
detail. For example, Vanderwolf et al. (1975) found "no
consistent phase relation" between RSA and sniffing in corre-
lating EEG and inhalation cycle for long periods during
which other details of exploratory behavior were not consid-
ered. But exploratory sniffing is a complex, epochal behavior
(Welker 1964), and the appropriate "level of detail" for
behavioral description must take into account both its
complexity and intermittency. Macrides (1974) and Eichen-
baum et al. (1979) observed a preferred phase relation
between inhalation cycle and RSA in short bouts of intense
480 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
sniffing of relevant olfactory stimuli. Others have found that
RSA phase is related to the onset of relevant auditory stimuli
(e.g., Thompson 1980). Each of these experimental paradigms
was characterized by great detail in timing, replication of
behavioral minutiae, and statistical qualification. Moreover,
the necessary selectivity of behavioral observation was guided
in each case by a theory of RSA involvement in stimulus
analysis. It is impossible to observe all ongoing behavior at this
level of detail; the selectivity of observation requires a focus
on particular behaviors and on their psychological relevance.
Furthermore, contrary to V&R's suggestion, behavioral
scientists do have quantitative tools for indirect observation of
psychological processes. For example, through clever manip-
ulation of reward contingency, Ranck (1974) and O'Keefe
(1976) discovered that some hippocampal neurons fire prefer-
entially where and when the subject does not find expected
reward. The key aspect of expectancy was not observable in
the gross behavior of the subject. The procedures suggested
here (selective detailed behavioral observation and indirect
observation of psychological process) might best be used in
combination to clarify behavioral correlates-of neurophysio-
logical phenomena.
Unfortunately, V&R's new synthesis of cortico-reticular
involvement in determining "when" behaviors happen is no
more sophisticated than the arousal theory it is meant to
replace. Perhaps by the tedious detail and trickery which are
trade to psychologists we will gain some insight into the subtle
questions about the EEG, such as, "why a slow rhythm (RSA)
during active, attentive behavior?"
Is hippocampal theta an artifact?
Glynne Hirschman
Department of Psychology, University of Cape Town, Rondebosch 7700,
Republic of South Africa
Following the interpretation of Green and Arduini (1954),
investigators commonly assume, as do Vanderwolf & Robin-
son (V&R), that hippocampal theta (RSA) indicates an acti-
vated hippocampus. This is by no means a universal senti-
ment, however. Several authors have suggested that theta in
fact reflects an inactive hippocampus (Bennett 1973; Black et
al. 1970; Douglas 1967; Grastyan et al. 1959) and, indeed,
recent evidence seems to support this contention.
1. Unit activity during paradoxical sleep (PS): PS presents
an ideal opportunity for assessing the activity of hippocampal
neurons with regard to theta, since virtually uninterrupted
theta is present throughout this state. Most studies have
reported a decrease in the rate of firing during PS (Delacour
1980; Mink et al. 1967; Ranck 1973), and discrepant findings
(e.g., Noda et al. 1969) have been clarified by Ranck's
distinction between projection (output) cells and interneurons
(Fox and Ranck 1975; Ranck 1973). With this classification it
has been convincingly shown that hippocampal output cells
are strongly inhibited during PS, while interneurons (which
are generally thought to inhibit output cells) fire rapidly.
Since it is only via its output neurons that the hippocampus
can exert any influence, the conclusion seems inescapable
that, in this case, theta indicates an inactive hippocampus.
2. Unit activity and theta during the waking state: In
general, findings have been equivocal: Some units increase
their rate of firing during theta, while others decrease it
(Lidsky et al. 1974; Mays & Best 1975; O'Keefe & Dostrovsky
1971). Delacour (1980), however, has been able to make a
more definite statement. He found that during the elicitation
of a classically conditioned neocortical desynchronisation
(which is usually associated with hippocampal theta) hippo-
campal Type I (output) units were clearly inhibited.
 Commentary /V anderwolf & Robinson: Reticulo-cortical activity and behavior
Certainly it is the conclusion of Ranck (1973) that different
output neurons are concerned with different types of behav-
iour, rather than the presence of theta. The only cells which
show a consistent activation during theta are interneurons.
While a recent study by Bland et al. (1980) disagrees with this
finding, it should be noted that they used urethanised
animals - a fact which makes interpretation of their results
difficult (Mercer et al. 1978).
It is perhaps not surprising that sampling the activity of a
minute percentage of neurons during the waking state (when
many stimuli occur simultaneously) does not present a clear
picture. To assess the general excitability level of large
numbers of neurons at any particular point in time it is
perhaps more appropriate to turn to evoked potentials. Segal
(1978), using unrestrained rats, produced evoked potentials in
the hippocampus by stimulating the hippocampal commi-
sural fibres. He found that during theta the primary wave of
the evoked potential was much reduced, while the late
component was enhanced. This result is consistent with the
interpretation that the output neurons (which are the first to
receive the commissural activation) are in a more inhibited
state during theta, while the interneurons (whose firing is
secondary to that of the output neurons) are in a more excited
state.
3. Amphetamine, which is routinely administered to
produce theta, has been shown to inhibit hippocampal unit
activity (Segal & Bloom 1976).
4. Theta can be recorded during locus coeruleus (LC)
stimulation (Macadar et al. 1974; Robinson et al. 1977) even
though such stimulation specifically inhibits what appear
from their firing characteristics to be hippocampal output
neurons (see Segal & Bloom 1976). [Note: Robinson et al.
(1977) have argued that theta production during LC stimula-
tion is due to current spread, but this presumably does not
alter the fact that LC-mediated inhibition is still operative.]
5. Both ablation (see Altman et al. 1973; Douglas 1967;
Kimble 1968) and stimulation studies (e.g., Bland & Vander-
wolf 1972a; Vanegas & FLynn 1968; Votaw 1960) implicate
the hippocampus in some form of behavioural inhibition, and
yet it is not theta, but low voltage fast activity (LVFA) in the
hippocampus which is associated with both behavioural and
spinal reflex inhibition (Yokoto & Fujimora 1964).
Taken together, the above evidence implies that, in the
hippocampus as elsewhere, it is EEG fast activity which
indicates activation; and since the output cells are large and
numerous, it is they that seem likely to most influence the
EEG. Certainly the elegant work of Steriade (1978) supports
this contention with regard to the neocortex. He has shown
clearly that it is the activity of the large output cells of the
neocortex that is closely related to neocortical LVFA. The
interneurons show the opposite behaviour, being active
during synchronous EEG activity.
Unfortunately, there is little work on unit activity during
hippocampal LVFA, but the work of Whishaw et al. (1978) is
suggestive. From their records it can be seen that as an
electrode traverses the hippocampus, fast activity (15-55 Hz)
is closely related to the pyramidal and granule cell layers. In
addition, theta was not markedly affected when approxi-
mately 90% of the granule cells were destroyed by X-
irradiation, but the amount of fast activity was reduced
dramatically.
The fact that theta is present when the output neurons are
inhibited presents somewhat of a puzzle - if theta is not
produced by the output neurons, what then does cause theta?
The possibility that interneurons (which do fire in phase with
theta) might be involved is weakened by the fact that they are
few in number (less than 1% according to Fox & Ranck
1975).
Thus, in the absence of a suitable neural substrate, I would
like to submit the rather radical proposal that theta may be an
artifact. Specifically, I would suggest brain movement as the
artifact-generator, since it has long been established as a
source of EEG artifact (see, e.g., Li & Jasper 1953; Walsh
1956), and can be produced by any agent which causes
fluctuations in cerebrospinal fluid pressure (e.g., respiration -
especially sniffing - heart beat, head movements, and vigor-
ous body movements). Support for this contention derives
from a series of experiments designed to investigate this
phenomenon (Hirschman, in preparation), the main points of
which can be summarised as follows:
(«) "Theta" could be produced in a dead rat (whose head
was fixed in a stereotaxic frame) by rhythmically squeezing
the thorax, or moving the body relative to the head.
(ii) Hippocampal tissue movement and the concomitant
EEG were recorded in lightly anaesthetised animals. Brain
movement was found to bear a one-to-one correspondence to
theta.
(iii) Under conditions of anaesthetisation heartbeat was
found to be ineffective in pulsing the brain. However, when
halothane anaesthesia was applied to the point of respiratory
depression, the consequent increase in strength of cardiac
contraction did produce neural tissue movement; and a well-
developed theta, which bore a one-to-one relation to heart-
beat, was seen.
(iv) Sniffing was found to be an especially effective cause
of brain movement and theta. A bout of sniffing was always
accompanied by theta, and each sniff corresponded to a theta
wave. Figure 1 illustrates the correspondence between theta,
hippocampal tissue movement, and respiration. The large
amplitude deflection resulted from a sharp intake of breath as
the animal changed from normal respiration to sniffing.
(v) In the awake curarised animal, theta was found to
follow the respirator setting, provided that the ventilation
pressure was adequate. This finding supports earlier reports
to this effect (Li & Jasper 1953) and contrasts with Komisa-
ruk's (1970) failure to find such a relationship. It seems
possible that the discrepancy is due to Komisaruk's underven-
tilating his animals, since his records show a close correspon-
dence between heartbeat and theta.
(tri) The freely moving animal represents a more complex
situation in that many other variables can produce brain
movement, thus obscuring the simple relationships observed
during anaesthetisation. Nevertheless, several authors have
noted a one-to-one correspondence between sniffing and
synchronous EEG activity in the unrestrained animal (Gault
& Leaton 1963; Komisaruk 1970; Lippold 1973; Macrides
1975).
(vii) Distortions introduced by the capacitative coupling of
the electrode to the electrolyte are especially important when
two or more variables combine to produce brain movement.
Under these conditions brain movement does not always bear
I
Figure 1 (Hirschman). Illustrating the correspondence
between theta (HPC), hippocampal tissue movement
(MOUbr), and respiration (RESP). The large deflection marks
the transition from normal respiration to sniffing. A one-
to-one correspondence between the three measures is present.
Cal: 500 nV, 1 sec.
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 481
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
a simple relation to the induced EEG fluctuations. Moreover,
it was found that theta produced by thoracic manipulation
could be blocked by LVFA. it is suggested that this blocking is
due to high levels of neural activity and thus that theta will be
seen only in a relatively inactive hippocampus.
(viii) The fact that theta has been found to be dependent on
the integrity of the septum (Green & Arduini 1954) may seem
to provide strong evidence that theta has an exclusive neuro-
biological origin. However, there are other possible explana-
tions. For example, the medial septal nucleus has been shown
to exert an inhibitory effect on the hippocampus (Miller &
Groves 1975). Thus its destruction will release the hippocam-
pus, resulting in excess neural activity and therefore a
predominantly desynchronised hippocampal EEG.
EEG, pharmacology, and behavior
Herbert H. Jasper
Department of Physiology, University of Montreal, Montreal, Quebec,
Canada H3C 3T8
Although I very much appreciate Vanderwolf & Robinson's
(V&R's) sincere efforts and their critical review, I believe that
there are too many points of question in their treatment of the
subject for me to deal with adequately in a brief commentary.
Furthermore, the complications of arguments based on phar-
macological evidence, of which V&R make extensive use, do
not, I believe, provide a very firm basis for conclusions. For
example, there is much evidence that the effect of atropine on
behavior and on the electroencephalogram is more compli-
cated than V&R would imply; if proper testing is carried out,
there are very significant alterations in behavior, and espe-
cially in learning processes, under the influence of atropine
accompanied by EEG slow waves. (Scopolamine, for exam-
ple, is used clinically to produce amnesia while maintaining
reactivity in patients during childbirth or surgery.) The
assumption that animals are as alert under atropine as under
normal waking conditions certainly does not involve a very
critical approach, yet it is one upon which much of the
evidence for V&R's evaluation of the arousal hypothesis is
based.
On the other hand, I do feel that the suggestion that more
than one transmitter may be involved, such as, for example,
acetylcholine and amino acids, is a very good one; we have
positive evidence that there is a remarkable change in the
liberation of amino acids from the cortical surface in arousal
as compared to sleep states, as well as marked change in
measures of acetylcholine. This would tend to favor V&R's
conclusions. The evaluation of the effects of the catechol-
amines is somewhat doubtful, however, since they may also
interact with either amino acids or acetylcholine; such inter-
actions have been thoroughly demonstrated.
The above is just a sample of some of the many complica-
tions involved in the evaluation of V&R's approach. The
neurophysiological mechanisms underlying the various
behavioral "states of consciousness" are more complex than
the original EEG arousal hypothesis presumed; however, the
apparent exceptions or "contradictions" in states designated
as "sleep " or "waking " do not contradict the hypothesis but
serve to indicate the need for more careful and critical
behavioral analysis of the mechanisms underlying the many
different behavioral states designated as "wakefulness" or
"sleep." V&R have made an important contribution in this
direction. [For further information see Jasper 1966; Celesia &
Jasper 1966; Jasper & Koyama 1967; Jasper & Krnjevic 1969;
Jasper & Tessier 1971; Reader, Ferron, Descarries & Jasper
1979.]
482 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
Understanding the physiological correlates
of a behavioral state as a constellation of
events
Barbara E. Jones
Laboratory of Neuroanatomy, Montreal Neurological Institute, Department
of Neurology and Neurosurgery, McGill University, Montreal, Quebec,
Canada H3A 2B4
Rather than creating a new synthesis of current concepts,
Vanderwolf & Robinson (V&R) merely reject an anachronis-
tic and oversimplified view of the relation of electrocortical
activity to behavior, thus setting up a strawman; moreover,
they do so with less rigor, offering a piecemeal model of the
brain reconstructed by surgical and pharmacological means
to explain pathological behavioral states.
With contemporary computer technology, a monolithic
analysis, involving a single physiological correlate of behavior
such as electrocortical activity, has now been superseded
(Friedman & Jones 1981). Through the quantification of the
amplitude or frequency of multiple physiological parameters
(including electrocortical activity, neck muscle tonus, eye
movements, ponto-geniculo-occipital spikes and yes, V&R's
preferred variable hippocampal activity), it becomes appar-
ent that all these physiological measures covary with observ-
able behavior through the sleep-waking cycle. Contrary to
V&R's statement, electrocortical activity, like each of these
variables, is indeed strongly correlated with behavioral state
in the normal animal. However, any one variable, including
behavioral phenomena (as V&R admit) is inadequate for the
reliable identification of the sleep-waking state. Instead, the
states of waking, (high amplitude) slow wave sleep, and
paradoxical sleep are defined and reliably identified as a
particular constellation of physiological and behavioral
events. In fact, through the simultaneous quantification of
multiple physiological variables (particularly electrocortical
activity, muscle tonus, and ponto-geniculo-occipital spikes),
cluster analysis algorithms have been successfully applied to
the computerized classification of the sleep-waking states in
the normal animal.
In an experimental animal with surgical destruction of the
cortex or pharmacological interference with the acetylcholine
receptors, the physiological and behavioral events of the
normal constellations are (and here I disagree with V&R)
truly dissociated. These pathological states should therefore
not be used (as they have been by V&R) to evaluate the
normal correlation between electrocortical activity and
behavior. Sleep, which is normally characterized by high
amplitude electrocortical activity, is no longer normal sleep
without cortical activity, even though one aspect, the behav-
ioral phenomena, may appear normal. Waking, which is
normally characterized by low amplitude electrocortical
activity is no longer normal waking when this activity
increases in amplitude with atropine, even though certain
superficial behavioral parameters might appear normal.
Studies would suggest, in fact, that the entire constellation of
events, including the behavior, has changed after these
manipulations. Recently, cluster analysis of multiple physio-
logical and behavioral variables has revealed a complete
alteration of the associations among these parameters after
brainstem lesions in the cat (Jones & Friedman 1981).
These pathological states have been more appropriately
used to determine the essential mechanisms for states or for
particular components of states. V&R have not taken into
account the existing suggestion that two different reticulo-
telencephalic systems may be important for tonic electrocor-
tical activation and behavioral arousal of the waking state (see
Jones, Bobillier, Pin & Jouvet 1973). By definition, it cannot
be denied that the reticulo-cortical system (as V&R call it) is
essential for the tonic cortical activation of waking. The fact
 Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
that other reticulo-telencephalic and reticulo-spinal systems
are necessary for behavioral arousal has already been demon-
strated.
As to the specific role of catecholamine neurons in waking,
(proposed by Jones et al 1973), numerous critical studies
involving selective lesion and pharmacological techniques
have permitted a full appraisal of their importance in arousal
and have thus made it necessary to assign a modulatory,
rather than an essential mediating, arousal function to these
neurons (Jacobs & Jones 1978). As V&R suggest, the re-
ticulo-telencephalic systems that underlie the regulation of
behavioral state are probably multiple and include as constit-
uents the monoamine neurons. As these authors emphasize,
pharmacological and biomedical evidence suggests that
acetylcholine neurons are also a component of re-
ticulo-telencephalic activating and arousal systems. However,
without histochemical identification and neuroanatomical
localization of acetylcholine neurons, they cannot be submit-
ted to the same rigorous physiological tests as have the
monoamine neurons (see Jacobs & Jones 1978). Therefore, to
formulate a model of the essential role of acetylcholine
neurons and their target cells in arousal, especially based
upon the action of one drug (atropine), is quite premature.
In summary, I would agree with V&R that multiple re-
ticulo-telencephalic systems, probably including monoamine
and acetylcholine neurons, contribute to the electrographic
and behavioral manifestation of sleep-waking states. But I
would suggest that these mechanisms should be approached
through a more holistic view, involving constellations of
physiological and behavioral events that define sleep-waking
states.
Rhythmic modulation of sensorimotor
activity in phase with EEG waves
Barry R. Komisaruk* and Kazue Sembab
'Institute of Animal Behavior, Rutgers University, Newark, N.J. 07102 and
'Department of Anatomy, College of Medicine and Dentistry of New Jersey,
Rutgers Medical School. Piscataway, N.J. 08854
A major conclusion of Vanderwolf & Robinson's (V&R's)
review is that hippocampal rhythmical slow activity (RSA) is
controlled by two different neural pathways, each of which is
active in a different behavioral context. In this commentary,
we point out certain limitations of the criteria on which V&R
base their conclusions, and discuss an aspect of RSA that they
have not addressed. V&R present evidence that, under appro-
priate conditions, two different pathways control hippocam-
pal RSA. In anesthetized rats, RSA that becomes activated
spontaneously or in response to sensory stimuli is blocked by
atropine. Atropine also blocks the RSA that occurs during
immobility when rats are awake (Type 2 behavior), so the
authors contend that this RSA has a neural basis in common
with that under anesthesia. They propose that this Type
2 - anesthesia RSA is under cholinergic control and is
involved in the "stimulus control of behavior." They contrast
this pathway with the RSA of "Type 1 - voluntary behavior"
(e.g., walking) that is abolished by anesthesia but not by
atropine and "appears to be related to motor activity."
This classification into two different RSA systems is unfor-
tunately not so clear-cut as V&R imply, even on the basis of
their own findings. They claim that Type 2 behavior, which
includes immobility is "ordinarily not accompanied by RSA."
However, the EEG recording shown in their Fig. 3 (upper
left) shows a pattern during the immobile (Type 2) condition
that they indicate is an RSA pattern and is sensitive to
atropine (Fig. 3, upper right). This points up an ambiguity in
their criteria for the occurrence of RSA, for sometimes the
authors emphasize its nonexistence (i.e., Type 2 behavior is
"ordinarily not accompanied by RSA") and other times they
emphasize its blockage (i.e., by atropine). Furthermore, there
is a question as to which components of the RSA are blocked
by atropine; in Fig. 3, upper right, although the waves do not
persist in a steady rhythm, 2 or 3-wave segments can
nevertheless be seen. There is also a problem regarding the
criteria for the absence of theta. For example, in Fig. 2 (lower
trace) in the example shown of hippocampal activity related
to Type 2 ("nontheta") behavior, evenly spaced wave crests
occurring at the theta frequency are evident. Thus, even in
this assumed absence of theta, rhythmic brain activity at the
theta frequency is nevertheless present. Thus the difference
between theta and nontheta activity may be quantitative
rather than qualitative.
However, let us assume that criteria can eventually be
identified that reliably distinguish two different RSA mecha-
nisms. A question then remains of whether these two mecha-
nisms are operational in the normal awake rat, and if so, what
their functions are. For example, are the cholinergic and
noncholinergic mechanisms both active in concert with each
other during Type 1 behavior? Do they mediate sensory and
motor patterns, respectively, in an integrated system?
We submit that a behavior pattern which is particularly
well suited to such an analysis has not been considered in
V&R's present discussion, although they raise questions about
the sensory and motor functions of RSA. This behavior
pattern is sniffing-vibrissal-whisking during exploratory
behavior. In this behavior pattern, which is almost invariably
associated with the Type 1 RSA activity, motor and sensory
systems are precisely coordinated with each other (see Komis-
aruk 1970). The motor patterns of inhalational sniffs and
protractions of the vibrissae generate sensory bursts of olfac-
tory and vibrissal tactile afferent activity. We have proposed
(Komisaruk 1970; 1977; Semba & Komisaruk 1978) that each
individual theta (RSA Type 1) wave can be viewed as a single
excitation cycle of systematically varying sensory and motor
neural excitability. These excitability cycles normally occur
one after the other, in rhythmic succession, forming the theta
rhythm. We have suggested that the function of this mecha-
nism is to enable the CNS to sample and respond to the
sensory environment in successive "bits." Characteristically,
although not invariably, there is one sniff cycle to one theta
wave in rats (Komisaruk 1970) and hamsters (Macrides 1975).
In rats, this one-to-one relationship is maintained over the
normal range of sniffing and theta frequencies (Komisaruk
1973).
The sensory "gating" property of the theta rhythm is
indicated by the finding that the number of unit action
potentials generated in the lateral hypothalamus by constant
current single shocks to the olfactory bulb varies systemati-
cally as a function of the phase of the theta rhythm at which
the stimulus was delivered (Komisaruk 1977). Similar effects
in hippocampal afferents have been demonstrated recently
by Rudell, Fox & Ranck (1980) and Buzsaki, Grastyan, Czopf,
Kellenyi & Prohaska (1981). Motor performance is also modu-
lated in phasic relation to the hippocampal theta rhythm.
Rats were trained to press a lever ad lib for a food pellet
reward. We found that they were most likely to press the
lever at the peak of their spontaneous concurrent theta wave,
and were most likely to withdraw their paw from the lever at
the opposite polarity peak of their theta wave (Semba &
Komisaruk 1978). Integration of sensory, motor, and atten-
tional processes in relation to the theta wave was demon-
strated by the study of Eichenbaum & Macrides (1979) in
which individual sniffing cycles and hippocampal theta
cycles became entrained and phase-correlated with each
other when stimulus salience was reversed in an olfactory
discrimination task. The authors concluded that entrainment
of sniffing and theta rhythms is involved in the assessment of
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 483
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
the significance of odors.
Modulation of sensorimotor activity in phasic relation to
brain rhythms appears to be a general phenomenon, as
demonstrated by similar findings in relation to the thalamo-
neocortical rhythmic EEC This approximately 9 Hz pattern
(which V&R call "spindle activity") appears in rats during
alert immobility ("freezing"). We have observed that it is
characteristically accompanied by a low amplitude tremor of
the vibrissae and occasionally of the lower jaw in the absence
of gross bodily movement (Semba, Szechtman & Komisaruk
1980). Both the vibrissal tremor and the EEG pattern cease
when the vibrissae are touched lightly. A remarkable syn-
chrony exists between each individual tremor movement of
the vibrissae, recorded as EMG (electromyogram), individual
neocortical waves, and individual bursts of neuronal activity
in the ventrobasal thalamic nuclear complex. We have identi-
fied this EEG pattern as "alpha rhythm" in the rat, on the
basis of its frequency, its neuroanatomical and functional
characteristics, and the behavioral context in which it occurs
(for further discussion, see Semba et al. 1980). It does not
occur during whole body tremor or tooth-gnashing (chatter-
ing). As in the case of the theta rhythm, phasic modulation in
relation to individual waves of the alpha rhythm has been
reported for sensory thresholds and reaction time (see Komis-
aruk 1977, for review).
The observations described above provide specific behav-
ioral endpoints that are correlated with specific brain EEG
paterns and could help provide insight into the sensory,
motor, and integrative mechanisms which V&R suggest are
differentially related to these EEG patterns. The findings of
phasic relationships between individual EEG waves and indi-
vidual muscular movements raise the basic question that the
authors have not addressed: What is the functional signifi-
cance of the rhythmic nature of the EEG patterns, the Type 1
RSA: 7-12 Hz; Type 2 RSA: 6 Hz; and neocortical spindle
activity during Type 2 behavior: 6-9 Hz. Since V&R have
raised the question of the behavioral correlates of these brain
rhythms, we suggest that whatever different behavioral
systems they may regulate, they may all share the common
property in which their excitability cycle, i.e., their afferent
sensitivity and efferent potency, fluctuates in relation to the
EEG wave phase. This may serve a variety of functions, such
as increasing the range of sensitivity to afferent excitation,
maximizing the degree of integration possible by increasing
the number of neurons available for excitation at certain
moments (e.g., wave peaks), and maximizing the ability to
excite postsynaptic neurons, by increasing the likelihood of
temporospatial summation via a synchronous barrage at the
wave peaks.
Cellular mechanisms of cholinergic arousal
K. Krnjevic
Departments of Physiology & Anaesthesia Research. McGill University,
Montreal. P.O., Canada H3G 1Y6
It is notoriously difficult to interpret "brain waves" (EEG
activity). When an attempt is made to correlate certain types
of wave activity with specific aspects of behavior - another
"phenomenon" that does not readily lend itself to precise,
objective analysis - the complications are further com-
pounded. One can therefore only wonder at the fearlessness
of authors who are willing to expose themselves to the
inevitable accusation of gross oversimplification. And yet this
kind of approach is important, because even if only tentative
conclusions may be justified at the present stage, they should
point increasingly toward more vigorous tests and better
hypotheses.
484 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
Since Vanderwolf & Robinson (V&R) emphasize the appar-
ent involvement of cholinergic pathways in behavioral arou-
sal, I would like to comment more specifically on cellular
mechanisms of cholinergic activation in the brain and why
they may be particularly involved in some forms of arousal.
In the first place, it is now clear that as a muscarinic
(atropine-antagonized) agent, ACh is not a simple transmitter
in the sense that ACh (nicotinic) is an all-or-none transmitter
of excitation in muscle. Its role can be characterized more
usefully as that of a modulator, because its primary action
appears to be to reduce membrane outward currents:
Normally, such currents tend to slow down neuronal depolari-
zation, thus impeding the generation of action potentials;
moreover, by accelerating repolarization after a Spike, they
also prevent repetitive firing. Hence, a depression of outward
currents facilitates excitation and promotes repetitive
discharges in response to single inputs. [See also Dismukes:
"New Concepts of Molecular Communication Among
Neurons" BBS 2(3) 1979.]
Two kinds of outward currents are now well known: One
set, the K currents, is intrinsic to the neuronal membrane,
being generated in response to depolarization. Cl" current on
the other hand, is elicited especially by inhibitory synaptic
action. There is now strong evidence that in structures such as
the neocortex and the hippocampus (and no doubt various
sites in the brain stem)ACh selectively inactivates these
outward currents through two different mechanisms.
The first is the muscarinic depression of neuronal K
conductance originally described in the neocortex (Krnjevic
et al. 1971), and even more recently shown to operate also in
the hippocampus (Dodd et al. 1981; Ben-Ari et al. 1981). In
both regions, ACh makes pyramidal-type neurons strikingly
more responsive to any form of depolarizing input (electrical
or synaptic). According to Brown & Adams's (1980) study of a
comparable muscarinic facilitation of sympathetic neurons,
ACh blocks selectively a special, voltage-dependent K current
("M-current") which is activated by small depolarizations
from the resting level, and is therefore normally particularly
effective in preventing repetitive discharges.
The second mechanism first became apparent in very
recent studies of the hippocampus (Krnjevic et al. 1980;
1981). It is especially evident when local applications of ACh
are combined with fimbrial stimulation. In rats under
urethane, very low frequency stimulation of the fimbria -
which activates both excitatory and inhibitory inputs to the
pyramidal cells of CA1 - does not lead to overt excitation, the
predominant response being strong inhibition (which
presumably masks the excitatory effect of EPSPs). When ACh
is applied, the previously inactive neurons generate large
population spikes, evidently because ACh weakens the inhibi-
tory suppressive action, thus "releasing" excitation. What is
even more significant from the point of view of V&R's target
article is that a similar "release" of population spikes is
provoked by medial septal stimulation (Ropert et al. 1980).
Thus, through two quite different mechanisms, one a
postsynaptic facilitatory influence and the second a presynap-
tic disinhibition, ACh enhances hippocampal responsiveness
to various inputs, presumably carried by more conventional
synapses. Although evidence of a disinhibitory action of ACh
in the neocortex is less compelling, it is likely that both kinds
of cholinergic facilitatory mechanisms also take part in
neocortical arousal (Steriade 1978).
There is increasing evidence that some other agents can
increase the responsiveness of certain (more peripheral)
neurons by diminishing K currents: For example, peptides
such as substance P (Krnjevic 1977) and luteinizing hormone
releasing hormone (Adams & Brown 1980), as well as mon-
amines such as noradrenaline and 5HT (VanderMaelen /
Aghajanian 1980); while another peptide, the opioid enke-
phalin, may also facilitate pyramidal firing in the hippocam-
 Commentary/Vanderwolf
pus by causing disinhibition (Zieglgansberger et al. 1979). It is
therefore conceivable that the atropine-resistant phenomena
described by the authors are mediated by some of these other
modulators.
Needed: More data on the reticular
information
Robert B. Malmo and Helen P. Malmo
Department of Psychiatry, Neuropsychology Laboratory, McGill University,
Montreal, P.O.. Canada H3A 1A 1
We have a strong conflict in commenting on Vanderwolf &
Robinson's (V&R's) paper. We so admire Vanderwolf's
pioneering work on moment-to-moment covariations be-
tween bodily movements and hippocampal EEGs that we
would like to praise that tremendous contribution and end the
commentary there. Behavioral monitoring of brain recording
is no longer an option, because failure to monitor is failure to
acquire indispensable data, and possibly results in erroneous
conclusions.
Data on the reticular formation. There is a curious inconsis-
tency between the choice of reticulo-cortical relations as their
central theme, and the relative neglect of the reticular forma-
tion (RF) in the research program of Vanderwolf and his
co-workers. They mention no RF recording from their labora-
tory, citing only one RF stimulation experiment from it, and
they refer to only one RF recording study (Vertes 1979). They
hardly mention any studies using multiple-unit (MUA)
recording from the RF in freely moving rats with behavioral
monitoring (Klemm 1971; Malmo & Malmo 1977; Schwartz-
baum 1975). Figure 1 shows a typical covariation of RF MUA
with head movement and body movement in a rat.
Dichotomy. It seems to us that in their commitment to the
Type 1-Type 2 dichotomy V&R have paid insufficient atten-
tion to the problem of relations between extent of skeletal-
Figure 1 (Malmo & Malmo). Decline in reticular formation
multiple unit activity (MUA) when rat stopped walking and
stood still. Top three lines: photographic recording of reticu-
lar formation MUA (from oscilloscope); fourth line: inte-
grated MUA; fifth line: head movement; bottom line: body
movement. Arrows indicate same moment in time. Horizon-
tal line: 2 sec for film and 5 sec for other 3 traces. Vertical
line: 200 jiV calibration for film. (From Malmo and Malmo
1977, with permission of Elsevier/North-Holland Biomedi-
cal-Press).
& Robinson: Reticulo-cortical activity and behavior
motor activity and degree of change in recorded brain
activity, which was studied earlier in Vanderwolf s laboratory
(Whishaw & Vanderwolf 1973) with positive results. Other
studies suggesting such correlations include EEG, MUA, and
unit recording (Arnolds, Lopes da Silva, Aitink & Kamp
1979a, 1979b, 1979c; Klemm 1971; Malmo & Malmo, 1977;
Schwartzbaum, 1975; Siegel, McGinty & Breedlove, 1977).
The reliance of V&R on visual inspection of analog records is
conducive to dichotomizing. Although they cite Arnolds et al.
(1979a, 1979b, 1979c) in defending eye-balling of EEG
records, Arnolds et al. themselves are extremely critical of
nonquantitative EEG analyzing and dichotomizing (Arnolds
et al. 1979a, p. 565). Black (1975) draws the following
conclusion (p. 154): "In general, the operational definitions of
'voluntary' and 'automated' are not clear; it often seems as
though 'voluntary' and 'automated' are defined post-hoc by
the correlation of hippocampal EEG patterns with a
response. " V&R themselves say, "Unfortunately, there are, as
yet, no clear behavioral criteria by which Type 1 or Type 2
behavior can be classified." Yet, throughout the article, they
write as though these behavioral criteria had in fact been
established. For example, in the paragraph preceding the
above quotation, V&R stated that Vertes (1979) demonstrated
"the existence of pontine neurons which fire in relation to
Type 1 behavior. . ." Actually, Vertes clearly states that the
firing of those cells (although concomitant with theta EEG)
was not specific to the kind of movement.
EEG recording too limited. Teitelbaum (1976) criticized
the hippocampal EEG electrode placements used by V&R,
and it does appear that their program would gain greatly in
flexibility if they were to use some other brain recording
techniques, such as unit recording or MUA. This would meet
Teitelbaum's objection that the atropine-resistant phenomena
may be artifacts of their electrode placement.
In some unpublished experiments we (Malmo & Mundl)
have stimulated the RF core serially with a descending
electrode while recording mean arterial pressure, heart rate,
and respiration and found circumscribed facilitatory areas
and depressive areas in the same vertical line of descent.
Therefore, the possibility exists for functionally identifying
two areas with reciprocal autonomic functions and then
recording from these two areas during atropinization, in
order to determine whether only one area was atropine
resistant. It appears that some kind of direct attack on the
problem like this is needed prior to claiming a new synthesis
involving the reticular formation, and one based on a
cholinergic-adrenergic differentiation.
Importance of recording head movement. Even when
sensitive body movement recording drops to baseline, head
movement often continues, and the covariation of head
movement and MUA (which we have found to be highly
significant) cannot be observed satisfactorily without a sepa-
rate recorder for head movement (Mundl & Malmo 1979).
The importance of observing head movements during record-
ing of brain activity has been stressed by Malmo & Malmo
(1977), by Siegel et al. (1977), by Teitelbaum, McFarland, &
Mattson (1977), and by Vertes (1979).
Quantitive neuropsychology. As O'Keefe and Nadel (1979)
say in agreeing with Bures, there comes a time when a
neuroethological approach should be followed by a "quantita-
tive neurophyschological approach." Correlation between
brain activity and behavior is higher for midbrain than for
forebrain (Malmo & Malmo 1977). Where along this
continuum does the hippocampus fall?
In RF MUA, what are the exceptions to positive covariance
between low RF MUA and quiescence? There are situations
in which immobility is associated with a high level of RF
MUA. One such situation is rising RF MUA preceding move-
ment (see Figure 1 for an example). Moreover, we have
designed appetitive situations that consistently produce high
THE BEHAVIORAL AND BRAIN SCIENCES (1981). 4 485
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
RF MUA in quiescent animals. What is the role of the RF
here? What are the species differences in correlations
between brain activity and behavior? To what extent can one
generalize from decorticate rats to decorticate primates?
What are the implications of the findings of Halgren, Rabb &
Crandall (1978) indicating that hippocampal RSA may be
lacking in humans? We wonder why these questions were not
considered by V&R.
Arousal theory. In human psychophysiology there is a
substantial amount of work on relations between quality (or
efficiency) of performance and accompanying physiological
activities (including quantified EEG). Some of this work has
involved the study of human brain-behavior relations with
the same kind of close behavioral monitoring as that of
Vanderwolf and his colleagues in their animal studies. The
behavior of the human subject was continuously monitored,
and EMGs (electromyograms) were recorded in addition (see
Malmo & Belanger 1967, pp. 309-10). The interest was in
recording tonic background activities (invisible without
instruments) in their relation to quality of performance. It
was in this experimental context that EMG gradients were
discovered (Malmo 1965). We believe that these psychophy-
siological experiments went well beyond the point of trying to
infer a psychological process. In fact, Goodman (personal
communication) was following up this line of research when
he recorded directly from the reticular formation of monkeys
during reaction time experiments. In multiple-unit recording
experiments, Goodman (1968) demonstrated the role of the
reticular core of the brain stem in generating supportive tonic
background neural activity for phasic acts. Goodman found
that there was a level of RF neuronal activity that was
optimal for reaction time performance. Above and below this
optimal level, performance was relatively poor. This work,
which was generated by arousal theory, used the kind of
objective methodology that V&R recommend. Yet it was not
mentioned. Furthermore, recent reviews of arousal theory
(Fowles 1980; Pribram & McGuinness 1975; and Thayer
1978) were ignored. Therefore, one can hardly regard the
V&R article as a comprehensive critique of arousal theory.
Acetylcholine, amines, peptides, and
cortical arousal.
J.W. Phillis
Department of Physiology, College of Medicine, University of Saskatche-
wan, Saskatoon, Saskatchewan Canada S7N OWO
In their fascinating exploration of contemporary opinion
regarding reticulo-cortical activity and behavior, Vander-
wolf & Robinson (V&R) expose a number of deficiencies in
the classical interpretation of arousal phenomena and substi-
tute an audacious new proposal. Their paper addresses itself
to some of the paradoxes which have plagued investigators,
such as how can a decorticate animal exhibit a wide range of
relatively normal behaviors, and why does an atropinized
animal display awake behavior simultaneously with a sleep-
type electroencephalogram? To account for these discrepan-
cies, the authors propose that there are two pharmacologically
distinct inputs from the reticular activating system to the
cerebral cortex and hippocampus.
One of these inputs, the traditional cholinergic arousal
system, may be responsible for the performance of normal
responses to environmental cues involving both learned and
spontaneous behavior. Responses in this category would
include behavioral immobility or simple reflexive or consum-
matory behaviors (classified as Type 2 behavior). The cholin-
ergic cortical arousal response can readily be elicited by
sensory stimulation in the absence of any accompanying
486 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
phasic motor activity.
The second arousal system, which is not affected by atro-
pine, is involved only if voluntary behaviors involving move-
ments such as locomotion and head turning (Type 1 behav-
iors) are being performed or if muscular twitches are occur-
ring during episodes of active (REM) sleep. The effects of this
system can be abolished by reserpine and are restored by the
administration of /3-phenylethylamine but not by L-dopa.
Further, since the effects of /3-phenylethylamine are not
abolished by dopamine or norepinephrine antagonists, it is
proposed that the /8-phenylethylamine interacts with an
unknown type of monoamine receptor. The endogenous
ligand for this receptor is unlikely to be j3-phenylethylamine,
which is not depleted by reserpine, and may be another trace
amine.
Experiments on acetylcholine (ACh) release have yielded
some interesting insights into the nature of the cholinergic
pathways to the cerebral cortex. ACh release occurs widely
from both cerebral hemispheres following unilateral stimula-
tion and is not restricted to the appropriate primary receiving
area of the cortex for a specific modality of stimulation
(Phillis 1968). Experiments in which forelimb nerves were
excited with graded stimute which evoked afferent volleys in
Group I, Groups I and II, Groups I, II and III, and Groups I,
II, III and IV nerve fibers clearly demonstrated that ACh
release is enhanced only by volleys in Group III and IV fibers
(Mullin & Phillis, 1975). Activity in Group III and IV fibers is
also a prerequisite for EEG desynchronization (Pompeiano
1973), and like its effects on the EEG, such stimulation elicits
a widespread increase in ACh release from both hemispheres.
ACh release is therefore clearly associated with cortical
arousal and the pathways involved must have an extensive
distribution to most, if not all, cortical regions. Attempts to
define the cholinergic input with electrophysiological tech-
niques have revealed the existence of a pathway from the
globus pallidus/magnocellular nucleus region of the basal
forebrain to the sensorimotor cortex (Edstrom & Phillis 1980).
Another pathway may project through the septum (Phillis
1974). There is also evidence for local intracortical choliner-
gic circuits (Phillis & York 1968).
It has been widely assumed that desynchronized electrocor-
ticogram reflects excitation of the underlying cortical
neurons. When applied iontophoretically, ACh inhibits many
of the neurons in the more superficial layers of the cerebral
cortex and excites only those in the deeper layers, including
the output, corticospinal neurons (Phillis 1974). EEG
desynchronization may therefore result from inhibition as
well as excitation of cortical neurons. This combination of
inhibition and excitation may serve to enhance the respon-
siveness of the output neurons to incoming thalamocortical
volleys. Activity in intracortical circuits which normally regu-
late the firing of the output neurons would be suppressed,
thus facilitating the action of other inputs.
Inhibition may be a prominent factor in the EEG desyn-
chronization elicited by stimulation of ascending catechol-
aminergic pathways to the cerebral cortex. When applied
iontophoretically bo*h norepinephrine and dopamine inhibit
the spontaneous firing of cerebral cortical neurons.
/?-phenylethylamine and a number of other trace amines also
have a depressant action on the spontaneous firing of cortical
neurons (Henwood et al. 1979) and this action may account
for the recovery of low voltage fast activity in the electrocorti-
cogram of reserpinized animals given /3-phenylethylamine.
A number of polypeptides present in the cerebral cortex
have pronounced depressive or excitatory actions on cerebral
cortical neurons; these included motilin, substance P, luteiniz-
ing hormone releasing hormone, vasoactive intestinal peptide,
somatostatin, cholecystokinin, thyrotropin releasing hormone,
and the enkephalins (Phillis & Kirkpatrick 1980). Little is
presently known about the putative peptidergic pathways in
 Commentary/Vanderwotf & Robinson: Reticulo-cortical activity and behavior
the cerebral cortex, but given their presence and the demon-
strable potency of these peptides, it is likely that they function
as neurotransmitters or neuromodulators in the brain.
Evidence is emerging that peptides are responsible for some
of the late slow synaptic potentials in sympathetic ganglia and
this may be the role that they fulfil in the brain. It seems
inevitable that peptidergic neurons will receive more atten-
tion in future analyses of the neural pathways involved in
EEG arousal. [See also Dismukes: "New Concepts of Molecu-
lar Communication Among Neurons" BBS 2 (3) 1979.]
An obituary for old arousal theory
James B. Ranck, Jr.
Department of Physiology, Downstate Medical Center, State University of
New York, Brooklyn, N. Y. 11203
Over thirty years ago the newly formulated theory of the
unitary relation of arousal to neocortical low voltage fast
activity and the midbrain reticular system was a major
advance. For the last ten years this theory has been quietly
dying. Its slow death has not been generally noted because the
theory does deal with important issues and, however inade-
quate, there has been nothing to substitute for this old arousal
theory. It has survived by default. As in politics, you can't
beat something with nothing. Over the last few years, and
especially in this target paper, Vanderwolf & Robinson
(V&R) have given us a substitute theory. Now armed with this
substitute, even with its problems, I for one, feel the old
arousal theory has finally died. I will therefore write about it
in the past tense. I will first drive some nails in the coffin and
discuss what was wrong with the theory, beyond what V&R
say. I will then discuss V&R's theory, i.e., as in any obituary I
will talk about the relatives which survive the deceased.
Thirdly, I will discuss their general approach, which is in
many ways more important than this specific theory.
1. What was wrong with the old arousal theory. It is
certainly the case that there are such things as behavioral
states, i.e., general characteristics of the animal beyond
specific stimuli or motor acts. An animal is more than just the
sum of all stimuli impinging on him and his responses to
them. Arousal, or something like that, is one of the important
behavioral states. Thirty years ago in many circles it was not
considered proper to talk about things like behavioral states.
However, since arousal seemed to have an electroencephalo-
graphic and anatomic correlate it gained a respectability it
would not have otherwise had.
In the last thirty years we have changed our standards of
how we can properly talk about behavior and we have
learned more about behavior and about the nervous system.
This theory has not kept up with these changes. I think the
presumed relation of arousal to EEG and the reticular forma-
tion inhibited clear behavioral definitions of arousal. In any
case, the arousal was not adequately defined behaviorally.
There are many behaviors for which I do not know the level
of arousal (e.g., in eating, REM (Rapid Eye Movement) sleep,
running a treadmill) and I do not know how to find out. I
cannot simply rely on EEG criteria. Arousal, or something
like it, deserves a clear behavioral definition independent of
neural correlates, otherwise the correlation cannot be tested.
Our knowledge of the nervous system also outgrew arousal
theory. The reticular formation is now known to be an area
mediating many specific functions, rather than being the
homogenous "activating center" of 1950. Single neuron stud-
ies of many parts of the midbrain and pontine reticular
formation do not show a simple relation to arousal (even if
one assumes it can be defined behaviorally). I think Siegel
(1979a) is close to being right in pointing out the strong
specific motor relations in the reticular formation. V&R point
out many errors in arousal theory. But these more general
problems made it unlikely that the theory could be patched
up. It had to be replaced.
2. The Vanderwolf & Robinson theory. V&R's theory recog-
nizes many behavioral states, but puts them into two major
categories in the awake state. This is surely an oversimplifica-
tion. However, an important advance is that V&R do not
introduce a one-dimensional spectrum (arousal) to span across
all awake states. Dividing awake states into two categories
naturally invites other categorizations within these states or
cutting across them. Since hippocampal theta rhythm has not
been unequivocally recorded in primates, a major difficulty
with V&R's theory at present is that it is not applicable to
primates. In addition, hippocampal theta rhythm has also not
been clearly seen in nonmammals, so that this limits its
applicability as well. We do not yet know the mechanisms of
the hippocampal theta rhythm or of neocortical low voltage
fast or rhythmic waves. Indeed the V&R theory only makes
correlations with slow waves and drug changes and behavior
and does not get much involved in mechanisms at all. If the
mechanisms were known, perhaps the theory could be
extended to nonmammals and primates.
Relatively nonmotor behaviors such as those they call Type
2 are not well defined by V&R. This is partly because of
V&R's general approach, as discussed in the next section.
However, these behaviors could be more sharply defined, and
should be, before the theory can be adequately tested.
For rats, which are the only nonhuman animals that I know
well, the V&R theory deals with much of the current data,
and can potentially be expanded to deal with more. Most of
the data V&R use to develop the theory is from rats; I would
like to see work on nonrats to test the theory fully in other
animals. I think the theory is the best we have now, so it
would be worth doing this work on other animals.
3. The nature of the V&R approach. Whatever may come of
their theory, V&R have produced major advance by their
approach. In Vanderwolf's landmark 1969 paper on rat
hippocampal theta rhythm, where the approach is perhaps
first used fully, the rat behavior is described in a variety of
situations. The key is that what is described is what the rat is
actually doing in detail, including very small movements.
This is in contrast to some descriptions of animal behavior
which only describe a few behavioral facts in a particular task
which the describer assumes are sufficient to demonstrate
that some internal process is occurring. Arousal was usually
described this way. In most published reports on arousal it
was difficult to find out much about what the animal was
actually doing or not doing. We were only told that the
animal was at a certain level of arousal. I, for one, often had
trouble understanding these descriptions. I did not find that
my estimates of a level of arousal were the same as those of
other observers. I could never be sure I was using the same
criteria as someone else, because there were only neocortical
electroencephalographic criteria, no clear behavioral criteria.
Vanderwolf and his many collegues have shown what can be
done by actually describing behavior.
There are difficulties with their approach, especially in
dealing with animals that are not very motoric, such as cats
and rabbits, or with largely immobile states such as attending
(which can in theory be defined behaviorally). In this target
article V&R seem more willing than usual to try to discuss
some nonmotoric activities. This will be an important
advance if they continue to apply their careful descriptions of
what an animal really does to less active behaviors.
V&R also really look at both neocortical and hippocampal
EEGs and describe what is there in simple terms ("measured
with a clear plastic ruler") rather than describing some highly
analyzed property of the EEG. Their approach to describing
the EEG is the same as their approach to describing behavior.
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 487
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
Any analysis throws some data away and makes inferences
about what are important properties to be retained and
examined. Their theory is the result of describing what is
really there in simple terms. I would like to see them do more
analysis along with their descriptions of raw data as they do
with behavior. Their simple approach is sometimes down-
right primitive. However, a simple, primitive approach is an
essential first step. It has too often been the case with others
that the simple first step of observating EEG or behavior was
ignored in order to get on with fancier analysis, and what
turned out to be the most important observations were lost.
The V&R approach is a good basis on which to build.
Significance of localized rhythmic activities
occurring during the waking state
A. Rougeul, J.J. Bouyer, and P. Buser
Laboratory of Comparative Neurophysiology, University Pierre el Marie
Curie, Paris 75005. France
Vanderwolf & Robinson's (V&R's) target article contains
some interesting hypotheses regarding hippocampal activity
in relation to behavior. It is possible that this conceptual
model, with two distinct systems for theta activity, one
resistant to atropine, the other nonatropine resistant, may one
day contribute to solving the riddle of correlations between
hippocampal activities and behavioral states, a problem that
has generated so many contradictions in the past decades. We
shall not consider this specific aspect of the paper, which goes
beyond our own domain of competence.
On the other hand, we shall briefly comment on points on
which we unfortunately disagree. One of V&R's theses is that
neocortical slow wave activity is not well correlated with
"arousal levels or conciousness." This assumption is based on
what we think is an oversimplistic view that neocortex
displays either desynchronized activity (their "LVFA") or
what they call "slow waves." Their paragraph 2a, where they
state that "a large number of investigators have shown that
slow waves and spindles frequently occur in neocortex during
various kinds of waking behaviors " is erroneous. Semantical-
ly, and physiologically, the terminology is unsound. The
rhythmic neocortical activities that were described during
waking by several groups, including our own (Roth et al.
1967; Rougeul-Buser et al. 1975, 1978, Bouyer et al. 1981) are
completely distinct from slow sleep activities. The latter
consist, as is well known, of two patterns, delta slow waves
(2-3 c/sec) and spindles. On the other hand, at least three sets
of rhythms could be recorded over the anterior cortex during
immobility of the animal (cat or monkey), none of those
displaying the least similarity with sleep patterns. One set of
rhythms (36 c/sec) occurs when the animal is in a high state
of vigilance (e.g., immobile and watching prey). These
rhythms develop over two foci of very restricted size, one
over the pericruciate cortex, the other over the anterior
suprasylvian cortex and only there, the rest of the neocortex
remaining in the LVFA state.
Another set of slightly slower (14 c/sec) rhythms appears
during a state (common in the cat) of "quiet wakefulness,"
with similar localization. Finally, when the animal becomes
drowsy, rhythms of a slower frequency (6 c/sec) occur with a
slightly more extensive distribution. Such rhythms all differ
from the sleep patterns; moreover, they can only be observed
if the electrodes are placed at the right places on the cortex. If
the electrodes are implanted elsewhere, especially middle
suprasylvian cortex, or marginal gyrus, which are the most
popular sites for ECoG (electrocorticogram) recording,
LVFA occurs, at least during the states of attentive behavior.
Therefore, the concept of "paradoxical alertness" is not
488 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
adequate, the more so since the waking immobility rhythms
have nothing in common with spindles or slow waves. Even
human EEG studies, performed with scalp electrodes and
hence with a very low spatial resolution, have long recognized
that the occipital alpha rhythm and the central "mu" rhythm
(the latter probably corresponding to the above described
frontal rhythms, see Jasper & Penfield 1949; Gastaut et al.
1967; Chatrian et al. 1959; Kuhlman 1978; Covello et al.
1975) correlate well with situations that are quite distinct
from sleep. Nobody would seriously identify these alpha or
mu "synchronized" activities with sleep patterns!
More generally, our working hypothesis (based on the
above-mentioned facts, as well as others) is that a number (not
yet completely determined) of thalamocortical sectors may
give rise to synchronized activities of limited extent over the
neocortex (let us call them "modular rhythms"). This devel-
opment takes place in connection with certain behavioral
conditions, especially states of selective attention (to either
visual or somatic stimuli). Due to their spatial restrictions,
these activities may be completely overlooked in a "standard"
ECoG recording when no special care is taken regarding
localization. Therefore, the development of "slow-activities '
(i.e., non-LVFA in V&R's classification) is by no means
paradoxical; it is just that if enough electrodes were placed on
the neocortex, we could presumably observe a considerable
number of different conditions under which one focal rhythm
or the other would develop, depending on the organism's
prevailing cognitive or conative state. It is only in the extreme
states of alertness, with or without movement (emotional
situations, fight or flight) that the whole neocortex would
eventually display generalized LVFA.
In sum, it is our feeling that if electrocortical correlates of
waking behavior are to be studied, "holistic" electrocortical
exploration has to be replaced by more refined and topo-
graphically well-defined investigations. If sleep studies have
been so successful, it is in part precisely because in this case a
limited number of electrodes may suffice, the whole neocor-
tex being in more or less the same electrophysiological state.
Our knowledge of the states of waking, with constant atten-
tional shifts, qualitative (selective) and quantitative (levels of
alertness), is far from complete; we are evidently dealing with
subtle and sometimes very short-term processes. We believe
that no clear correlation with ECoG will be established unless
these focal rhythmic systems are better known, and only if
"recording electrodes [are] placed correctly in the generator
zone." (A quotation from V&R, but unfortunately only with
reference to the hippocampus!).
With these considerations in mind, we must indicate our
disagreement with this part of V&R's "critique of the arousal
theory."
Neocortical activation and adaptive
behavior: Cholinergic influences
P. Shiromani and William Fishbein
Psychobiology Laboratory, Department of Psychology, City College of the
City University of New York, New York, N. Y. 10031
Over the years, we have followed with a great deal of
enthusiasm the efforts of Vanderwolf & Robinson (V & R)
toward understanding the role of the ascending reticular
system in behavior. We believe that their work has crucial
importance because it shows how purposive and reflexive
forms of behavior correlate with activity in the hippocampus,
neocortex, and the reticular system. We have some new data,
however, which raise some questions about their conclusion
that the "ascending reticulo-cortical pathways are not
directly involved in the basic phenomena of sleep, arousal,
and waking."
 Commentary/VanderwoN & Robinson: Reticulo-cortical activity and behavior
All the amassed evidence suggests that cholinergic mecha-
nisms are implicated in neocortical activation. However,
research on the cholinergic system has been handicapped,
from the outset, primarily because of the inability to localize
and map cholinergic pathways in the CNS. This research may
be gaining momentum as a result of recent advances in
detection of cholinergic receptor sites. For example, Lewis et
al. (1980), using a new autoradiographic technique, have
localized muscarinic receptor sites in the rat brainstem. One
area that was found to contain a high concentration of
autoradiographic grains was the pontine reticular formation.
This finding fits nicely with our own data (Shiromani &
Fishbein 1980). In our experiments, with rats, carbachol or
scopolamine is infused, via an Alzet mini-pump, into two
pontine nuclei: Reticularis Pontis Caudalis and the Giganto-
cellular Tegmental Field (FTG). The results show that carba-
chol augments active (paradoxical) sleep, i.e., hippocampal
RSA and neocortical LVFA, for at least five days while
scopolamine decreases it. The augmentation is due primarily
to an increase in the active sleep cycle frequency and not
because of an increase in its duration. Further, the augmenta-
tion due to carbachol is seen mainly during the night cycle,
when the animals are normally awake, while scopolamine
acts mainly during the day cycle, when the animals are
normally asleep.
Our findings, taken together with other cholinergic stimu-
lation data (Baxter 1969; George et al. 1964; Hobson &
McCarley 1977), as well as electrophysiological results from
pontine nuclei (Vertes 1979), would seem to suggest that the
eholinergic component of the ascending reticular pathway,
probably originating in the pontine reticular formation, is the
trigger responsible for hippocampal theta and cortical activa-
tion during both waking and active sleep.
Might the cholinergic pathways be involved in adaptive
behavior? We agree with V & R that the evidence so far
suggests that alterations of central cholinergic function
improve or impair learned and spontaneous behavior.
However, we must point out that these results come from
experiments in which the acetylcholine modulating agents
were administered peripherally. To our knowledge there is as
yet no study demonstrating that injection of acetylcholine
agonists/antagonists directly into the cholinergic reticular
system alters adaptive behavior, and most specifically
memory. Until this is known, we can only speculate about
how the activity in this pathway determines the rate of firing
of hippocampal theta cells (Ranck 1975) and association
cortical interneurons (Steriade 1978), which in turn may
influence the durability of the memory trace.
Reticular formation, brain waves, and coma
George G. Somjen
Duke University Medical Center, Department of Physiology, Durham, N. C.
27710
In 1959 Aclametz reported a very basic and important discov-
ery. He found that if the midbrain reticular formation of a cat
is destroyed, not at once, but in two or more stages one to
three weeks apart, the animal does not go into coma after the
operation and its sleep-wake rhythm is not disturbed. The
finding was confirmed by Chow & Randall (1964), and was
then peculiarly ignored. Two quite fundamental and so far
unanswered questions are raised by this observation. First,
what is the real reason that bilateral acute destruction of the
midbrain reticular formation invariably causes coma lasting
at least three to four weeks? And, equally important, why
does the same lesion inflicted in two stages not have the same
effect? Comparing the condition to spinal shock, or calling it
"diaschisis" may amplify the question, but does not answer
it.
Vanderwolf & Robinson (V & R) present an admirably
argued case for abandoning the accepted notion that the
degree of desynchonization (or LVFA) of the electrocortico-
graphic activity of the neocortex is a reliable measure of the
level of alertness. They also succeed in rendering plausible
their own concept of a duality of the LVFA state, controlled
by two different systems, and subserving different functions.
In the light of the report by Adametz (1959) one must,
however, question whether either or both of the LVFA states
defined by V & R is dependent on input from the reticular
formation to the forebrain. The two-stage lesion of the
midbrain reticular formation, described by Adametz (1959),
presents a gold mine of opportunity for neuropsychological
experimentation. Hippocampal and neocortical ECoG (elec-
trocorticogram) recording, behavioral experiments, and drug
studies on such lesioned subjects suggest themselves in such
variety that it would exceed the limits of this commentary to
detail them.
There is another quite different point of V & R's paper
worth discussing. One must wonder whether there are truly
sufficient reasons to abandon the concept that synchronized
rhythmic activity in the 0.5-15 cps frequency range repre-
sents an "idling rhythm" of unengaged neuronal populations.
Two considerations are relevant here, one a point of fact, the
other of theory. The slow-wave activity of neocortex observed
under the influence of atropine in apparently awake animals
is rather different from the sleep spindles and delta waves
seen in natural sleep, under general anesthesia, and in the
coma caused by bilateral midbrain lesion. Furthermore, Elul
(1972) has presented theoretical evidence that, in order to
produce electrical waves detectable by surface electrodes, it is
sufficient for a fraction of the available neuronal pool to be
engaged in synchronous activity; the remainder could be
desynchronized and remain undetected in conventional EEG
or ECoG recordings. This realization may be the key to the
apparent dissociations of behavior and ECoG. Atropinized
animals presumably do show neuropsychological deficits. The
behaviors that seem relatively intact may be performed by
neuron populations which discharge in "desynchronized"
patterns; the deficiencies in performance may be due to the
"idling" of those cells which generate the large amplitude
slow waves.
EEG desynchronization is associated with
cellular events that are prerequisites for
active behavioral states
M. Steriade
Laboratory of Neurophysiology, Department of Physiology, Faculty of
Medicine, Laval University, Quebec, Canada GIK 7P4
Many concepts have had a rough time before being accepted.
Tribulations have often been due either to the absence of
appropriate tools for testing a hypothesis when it is formu-
lated or to misinterpretations of the original idea. Both of
these conditions have attended Moruzzi & Magoun's (1949)
pioneering work. The concept of generalized reticular activa-
tion was taken by a thirsty audience to imply ubiquitous
ascending projections of (unknown) reticular origin, acting in
a diffuse excitatory way on (all) postsynaptic targets. The
reticular formation was viewed at the time as an undifferen-
tiated structure. Its neuronal networks were left ill defined
because they were not thought to be amenable to morphologi-
cal and electrophysiological analyses. This caused temporary
neglect of the concept of a reticular activating system. The
revived interest in the reticular formation during the last
decade is due to the advent of morphological methods which
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 489
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
circumvent the problem of passing fibers and to the develop-
ment of electrophysiological techniques which allow one to
record the activity of identified neurons in behaving animals.
Another source of confusion has been that, after Moruzzi &
Magoun's 1949 paper, the descriptive term "EEG desyn-
chronization ' and the behavioral notion of arousal were
sometimes used interchangeably by physiologists working on
the thalamus and neocortex of acutely prepared animals. This
was obviously an unjustified leap-one made by many of us.
Moruzzi & Magoun (1949) reported experiments performed
under conditions in which no behavioral observation was
possible; they described the reticularly elicited activation of
the EEG, and, aware of T. H. Huxley's dictum that those who
decide not to go beyond facts rarely get far, they advanced
their theoretical concept. But nowhere in that paper was EEG
desynchronization equated with waking or EEG synchroniza-
tion with sleep. As a rule, the difference in level between
electrical activity and behavior has been cautiously stressed
by Moruzzi in subsequent publications: "The main idea is to
make a sharp conceptual distinction between EEG synchroni-
zation and sleep, ' and "Clearly EEG synchronization reveals
. . . a process that must reach a critical level to give origin . . .
to genuine manifestations of sleep ' (Moruzzi 1972, p. 136).
The critique of the arousal theory in the target article is
based on some data leading to the claim that the desynchron-
ized and synchronized patterns of EEG rhythms are not well
correlated with "arousal" and "sleep." The first and most
striking example chosen is the EEG desynchronization that
occurs during a behavioral state (active sleep) associated with
a sleeping posture and relative unreactivity to stimuli.
Towards the end of their paper, however, Vanderwolf &
Robinson (V & R) reach the reasonable conclusion that, in
fact, "brain activity and patterns of motor output during
active sleep are quite similar to the patterns that occur during
waking." In other words, active sleep is not a depressed or
extreme type of slow-wave sleep, but a true yet paralyzed
arousal (Jouvet 1972), a state with a high degree of reticular
activation (Moruzzi 1972). These views have been tested in
my laboratory and demonstrated to be valid at a cellular
level, as discussed later in this commentary. So, there is no
surprise that EEG desynchronization accompanies active
(dreaming) sleep, a state to which the qualification of "abject
mental annihilation" in Eccles's opening remarks to the
symposium on The Nature of Sleep (1961) certainly does not
apply. Along with the same class of EEG-behavioral dissocia-
tions it is not fair to cite the case of desynchronized EEG
rhythms of the midpontine pretrigeminal cat in the context of
deep coma following brainstem injury (V & R's point lc). The
transected animals were carefully tested in the studies of the
Pisa group and "a genuine state of alertness was present when
the EEG was desynchronized" (details in Moruzzi 1972, p.
27), including the possibility of elaborating conditioning and
differentiation in chronic midpontine pretrigeminal prepara-
tions (see Zernicki's findings in his review, 1968).
Is the ascending reticular activation hypothesis invalidated
by recent developments? If we discard the unjustified EEG-
behavioral extrapolations mentioned above, we find that the
evolution of research has not only confirmed the data of
Moruzzi & Magoun's paper (1949), but it has fully justified its
major theoretical proposal: "The presence of a steady back-
ground of . . . activity within this cephalically directed brain-
stem system . . . may be an important factor contributing to
the maintenance of the waking state, and absence of such
activity in it may predispose to sleep" (p. 470, italics mine).
High levels of reticular activity in rostrally projecting
elements should not be viewed as responsible for all behav-
ioral components of arousal, but may create "the conditions
for the organism to be actively interested in the outside
world, . . . the readiness to receive only some kinds of stimuli
490 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
to the exclusion of others and to perform the motor patterns
of one definite instinct" (Dell 1958, p. 198). If changes in
ascending reticular influences are hypothesized to prepare
conditions for the occurrence of genuine behavioral compo-
nents in wake-sleep states, it would be worth studying the
cellular correlates of EEG desynchronization and synchroni-
zation processes to determine (a) whether or not neuronal
events in thalamocortical systems adequately account for
what we expect from an activated or deactivated state, and
(b) what are the most likely brainstem neuronal candidates
endowed with tonic ascending activating influences (reticular
in the classical sense or the more recently discovered
monoaminergic systems?) It is clear that point (a) takes for
granted that the activity in the thalamus and neocortex is
relevant to complex phenomena of waking and sleep. I
understand that decorticate rats may display head move-
ments, walking, and rearing, but I assume that waking
processes transcend this repertoire.
If the reticular activating concept were valid, one would
expect improved receipt of messages and performance of
commands either with artificial stimulation of the rostral
reticular core or during naturally occurring active behavioral
states. What are the correlates of adaptive behavior at a
cellular level? Basically, synaptic transmission in thalamic
nuclei and cortical areas should be facilitated, output
elements (such as pyramidal tract cells) should be in a state of
adequate depolarization for a quick response, and inhibitory
mechanisms should act efficiently to provide accurate
discrimination combined with rapid recovery. All these
events have been demonstrated to characterize identified
thalamocortical and corticofugal neurons during reticularly
induced EEG desynchronization, natural waking, as well as
active sleep.
Figure 1A shows the increased rates of spontaneous
discharge and the enhanced responsiveness in a corticothal-
amic cell during waking and active sleep. This is now a
general finding for long-axon neurons in various thalamic
nuclei and for corticospinal, corticopontine, and corticothal-
amic cells recorded from motor, somatosensory, and associa-
tion areas (see review by Steriade 1981). Also, the time-course
of inhibition varies with changes in the state of vigilance. A
powerful inhibition of cellular responsiveness follows the
initial excitation. The duration of the inhibitory period is
shorter and cyclic inhibitory-rebound sequences are blocked
during midbrain reticular stimulation and natural waking, in
both thalamic and cortical long-axon neurons (Fig. IB). It
follows that the whole sequence of events triggered by a
stimulus is telescoped during EEG desynchronization (Fig.
1C). The fact that inhibition is very sharp in the waking state
and recovers much faster than in slow-wave sleep provides a
mechanism subserving accurate control of thalamic and corti-
cal performances, and allows neurons to follow rapidly recur-
ring activity (Steriade & Deschenes 1974).
Some of the above cellular correlates of activated states,
namely the increased firing rate and enhanced somatic
responsiveness, can be detected in intralaminar thalamocorti-
cal neurons some 10 seconds before EEG desynchronization
in natural transitions from slow-wave sleep to waking or
active sleep (Steriade & Glenn, in preparation). Conversely,
in the transition from waking to slow-wave sleep, long inhibi-
tory periods can be seen during drowsiness in precentral
neurons of the behaving monkey, prior to overt EEG and
behavioral signs of slow-wave sleep (Steriade et al. 1974).
Long inhibitory pauses provide a mechanism for closing
sensory channels. Testing the excitability of lateral thalamic
nuclei during the sleep-waking cycle reveals that monosynap-
tic responses to afferent volleys are inhibited as of the first
sign of drowsiness (Steriade et al. 1969). Such deafferentation
in thalamocortical systems is a necessary prelude to attaining
 Commentary/Vanderwotf & Robinson: Reticulo-cortical activity and behavior
2ms
5QJ U8/S 13.1/S 30.1/s
w s D processes and described above. The effects consist of hyper-
B polarization and decreased spontaneous firing in neo- and
rr •
SYNCHRONIZED
Figure 1 (Steriade). Somatic responsiveness and inhibitory
events in thalamic and cortical neurons during states asso-
ciated with EEG desynchronization and synchronization. A:
A cell in parietal association area 5 of chroncally implanted
cat, antidromically invaded from the center median thalamic
nucleus; the antidromic responsiveness was investigated with
a four-shock train at 225/s, with an intensity 30% above
threshold allowing fluctuation in response probability; at that
intensity responsiveness increased from the first to successive
shocks in the train; graph depicts the percentage responsive-
ness (ordinate) to the first, second, and fourth shock during
waking (W), synchronized sleep (S), and desynchronized
sleep (I)); the mean rate of spontaneous firing (per second) is
also indicated. B, 1: Periods of suppressed firing (a, b, and c)
and postinhibitory rebounds in a lateralis intermedius tha-
lamic neuron following single-shock stimulation of cortical
area 5 (arrow); and 2: the effect of a preceding train of
high-frequency pulses to the midbrain reticular core; note
reduced duration of the period of silenced firing and disap-
pearance of the c period. C: Simplified diagram to show the
whole sequence of excitatory-inhibitory events in thalamus
and cortex during EEG synchronization and desynchroniza-
tion; the changes during states characterized by EEG
desynchronization consist of: enhanced primary excitation
due to antidromic (or monosynaptic) volleys, diminution of
the secondary synaptic excitation (dotted part), sharp inhibi-
tion but with reduced duration (black part) and blockade of
rhythmic inhibitory-rebound sequences (modified from Ster-
iade 1981).
the critical level at which genuine manifestations of sleep
may occur.
As to the question (b) concerning the neuronal aggregates
subserving activating influences on thalamocortical systems,
one should first note the difficulties in interpreting experi-
ments involving electrically stimulating and lesioning the
reticular formation (which may have affected passing fibers
arising in nonreticular neuronal aggregates) and the discovery
of extensively ramified monoaminergic systems; these have
together generated a challenge to the reticular concept as well
as hypotheses concerning the role of serotoninergic, dopamin-
ergic, or noradrenergic systems in mediating different
components of arousal and waking behavior. Restricting the
discussion to tonic activation processes, several aspects should
be borne in mind:
(a) Electrical stimulation of the raphe system and locus
coeruleus complex, as well as iontophoretic application of
5-hydroxytryptamine and norepinephrine, induce cellular
phenomena opposite to those observed in forebrain activation
allocortical neurons; identified corticospinal neurons are
inhibited by locus coeruleus stimulation, an effect opposite to
that of cholinergic excitation of these elements and to wake-
fulness (Phillis & Kostopoulos 1977; Stone et al. 1975).
(b) The other difficulty in considering monoaminergic
systems responsible for tonic ascending activation phenomena
is the following: Long-axon thalamic and cortical neurons
display essentially the same activity during both wakefulness
and desynchronized sleep (see above), while raphe and coeru-
leus neurons have opposite behaviors during these two states:
highest discharge rates in waking and lowest in active sleep
(McGinty 1973; Hobson et al. 1975).
(c) Finally, the failure to induce any change in EEG
desynchronization following bilateral destruction of the locus
coeruleus complex with 85-95% depletion of cortical norepi-
nephrine, together with other experimental data, lead to the
conclusion that monoaminergic neurons do not mediate tonic
EEG activation (data also cited in V & R's target article).
While the effects of locus coeruleus stimulation are not
consistent with what is expected from a presumed tonic
activating system, their involvement in specific components
of activated states should not be discounted. The most inter-
esting action might result in an increased signal-to-noise ratio
(Foote & Bloom 1979) or in switching emphasis from one set
of inputs to another (see Dismukes 1979).
Returning to the classical hypothesis of a cephalically
directed influence arising in the midbrain reticular forma-
tion, we find good reasons to concentrate the search for
neuronal candidates underlying tonic activation at this level.
The midbrain reticular formation is characterized by well-
defined ascending projections and direct routes for transfer-
ring reticular excitatory influences to cortically projecting
thalamic neurons. Midbrain reticular neurons with identified
rostrally projecting axons exhibit tonic discharge features and
higher firing rates during active behavioral states, compared
to slow-wave sleep. It is noteworthy that such neurons show a
statistically significant increase in discharge frequency 15
seconds before the end of slow-wave sleep epochs that
develop into awakening (data in collaboration with Oakson &
Ropert, in preparation). Although this analysis discloses a
temporal but not necessarily a causal relation, it suggests that
midbrain reticular neurons play a leading role in the transi-
tion from synchronized sleep to activated behavioral states. It
is obvious that the properties of midbrain reticular neurons
are very unlike those of pontine reticular neurons that prefer-
entially discharge during movements in waking and during
REM's in active sleep (cited in the target article). We tested
the ascending activating reticular influences for which the
criterion of tonic activity is of major importance (Moruzzi
1972) and, therefore, discarded periods with phasic motor
events which may introduce uncontrolled factors into the
evaluation of discharge due to the proprioceptive feedback
generated by movement itself.
From the midbrain reticular core, ascending axons contact
and excite neurons in medial (centrum medianum-parafas-
cicularis, CM-Pf; and ventralis medialis, VM) and intralami-
nar (centralis lateralis-paracentralis, CL-Pc) thalamic nuclei
with direct projections to neocortex (Glenn & Steriade, in
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 491
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
preparation). Inputs to VM are important as this nucleus is a
source of a contingent that terminates almost exclusively in
layer I of neocortex in both rat (Herkenham 1980) and cat
(Glenn, Hada, Roy, Deschenes & Steriade, in preparation), as
expected for a thalamic nucleus transferring reticular influxes
and exerting modulatory influences over widespread cortical
areas. The recent findings by Hyvarinen et al. (1980), show-
ing that the effect of attentive behavior is particularly
pronounced in the elements recorded at the junction of
cortical layers I and II of the monkey, fit well with the
evidence for an activating superficial thalamocortical projec-
tion. [See also Lynch: "The Functional Organization of Poste-
rior Parietal Association Cortex" BBS 3(4) 1980.]
Let me conclude that there is good evidence that ascending
reticular projections provide an important source for poten-
tiating thalamic and cortical processes that are prerequisites
for behavioral components of activated states. Moruzzi &
Magoun's concept is alive and well.
A ghost in a different guise.
R. J. Sutherland, I. Q. Whishaw and B. Kolb
Department of Psychology, The University of Lethbridge. Lethbridge,
Alberta. Canada T1K3M4
Hebb (1972), in his Textbook of Psychology, makes two
points about theories of how the nervous system works. The
first is that these ideas are important in determining the kind
and quality of research conducted; the second is that it is
important that we must not actually believe that these ideas
are correct. Vanderwolf & Robinson (V & R) have done a
laudable job of indicating why we should not believe the
traditional account of the reticulo-cortical arousal system and,
perhaps more importantly, how careful descriptions of behav-
ior must play a crucial role in elucidating brain function.
(They should also have mentioned that it is surprising that this
view ever obtained prominence since Goltz - summarized in
Luciani, 1915 - in widely publicized experiments in 1892 had
observed sleep-waking cycles and the various postures and
phasic motor patterns of the waking state in decorticated
dogs.) Despite our complete approval of these fundamental
aspects of V & R's paper, we feel the necessity of attending to
Hebb's second point; that is, we would like to indicate why we
do not believe the "new synthesis."
On a general level, their suggestions that the atropine-
sensitive reticulo-cortical system plays a role in "stimulus
control" or in making "normal responses to environmental
situations," that the atropine-resistant reticulocortical system
may play a role in "the control of Type 1 behavior," while the
cerebral cortex determines "the occasions on which particular
motor patterns are to be displayed," are hopelessly vague. A
moment's reflection should convince anyone that we could
characterize each part of the nervous system, from the
receptor cells in the retina to the ventral horns of the spinal
cord, in such a fashion. In order to be helpful in generating
research, the new synthesis must be made more explicit, even
though (given Hebb's dictum) we won't believe it.
More specifically, V & R claim that because sleep, arousal,
and waking behavior patterns occur in decorticate rats, the
reticulo-cortical projections are not essential for these aspects
of behavior. They may not be essential for an animal without
a cortex, but they may be necessary for an animal that still has
a cortex. So far, no one has ever observed an animal following
removal of only the ascending reticulo-cortical projections;
decortication removes these ascending systems, as well as the
descending cortical output. Following Hughlings Jackson, we
believe that the control over these aspects of behavior is
organized at each level of the nervous system, including the
492 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
cortex, but that the behavioral significance of the control
processes changes from level to level. First, as evidence for
this view, we can cite the observations that damage to
ascending catecholamine systems (by 6-OHDA) produces an
akinetic rat (without a circadian rhythm in its postural
adjustments). Removal of the neocortex of such a rat produces
an immediate release from the akinesia and results in hyper-
activity; administration of atropine can produce a similar
effect in these rats (unpublished observations; Schallert,
Whishaw, Ramirez & Teitelbaum 1978). Removal of both
ascending and descending pathways together may thus mask
a possibly opposing contribution that each makes to behavior.
Second, decortication definitely does have an effect on sleep-
waking behavior patterns and phasic motor patterns during
the awake state. We have observed that decorticate rats often
sleep out in the open when a sheltered spot is available, adopt
unusual postures during locomotion, swimming, eating, etc.,
do not retain normal tongue or mouth movements, and are
hyperactive in many situations (Vanderwolf, Kolb & Cooley,
1978; Whishaw, Nonneman & Kolb 1980; Whishaw, Schallert
& Kolb, in press). From a Jacksonian perspective of functional
hierarchies, it is not the case that the "motor score" for
behavior patterns is subcortically represented and that the
cortex decides when to act, as V & R suggest, but rather that
the cortical and subcortical mechanisms differ in terms of the
nature of the resident control processes - the environmental
triggers and guidances involved in the movements (Whishaw
et al. in press).
In regard to the suggestion that the atropine-sensitive
reticulo-cortical system is involved in "stimulus control" it
should be noted that this probably cannot be a general or
unitary involvement, although it is easy to find examples of
loss of stimulus control after lesions that damage this system,
the following examples indicate the presence of enhanced
stimulus control over elicitation, guidance, and reinforcement
mechanisms: (1) the decorticate displays heightened startle
responses to a variety of stimuli and exaggerated relaxation
and activation by warm and cold water, respectively; (2)
atropine-treated rats show enhanced guidance of locomotion
and head movements by snout contact with surfaces (Schal-
lert, De Ryck & Teitelbaum 1980; Whishaw et al. in press,
and (3); decorticate rats and rabbits show enhanced stimulus
control and cross-modality discrimination in Pavlovian condi-
tioning procedures and are capable of learning in instrumen-
tal conditioning procedures (Oakley 1979).
A final criticism concerns the notion that the deficits
observed in decorticate animals (e.g., in feeding, food hoard-
ing, nest building, mating, etc.) indicate that the cortex (or
some of its input) exhibits a general function. This is only
acceptable if these behavioral deficits cannot be doubly
dissociated (Teuber 1955) and associated with specific local-
ized cortical damage. It is now known, however, that many,
and possibly all, of the deficits observed to follow decortica-
tion also follow damage to discrete cortical regions (Kolb &
Whishaw 1978). For example, deficits in food hoarding,
feeding, and nest building are produced by frontal, but not
posterior, cortex lesions in rats (Kolb & Whishaw 1978; in
press). If there are actually no deficits after decortication that
indicate the loss of some general function (as we suspect),
then there certainly is no compelling reason to search for a
neuroanatomical substrate for it. In fact, through the history
of neuropsychology, this well-travelled general function has
migrated from the pineal with Descartes, to the cerebrum
with Flourens, to the cerebral cortex with Lashley, to the
right cerebral hemisphere with Semmes and others (Kolb &
Whishaw, 1980), and now to the reticulo-cortical pathway
with V & R. We believe that this ghost will finally come to
rest only with continued careful behavioral studies concern-
ing the specific functions of each particular neural system.
 Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
Where does the cholinergic modulation of
the EEG take place?
J. C. Szerb and J. D. Dudar
Department of Physiology and Biophysics, Dalhousie University, Halifax,
N.S., Canada B3H4H7
The finding of a relationship between the susceptibility of
EEG rhythms to antimuscarinic drugs and two types of
behavior described by Vanderwolf & Robinson (V&R) is an
important new development in our understanding of brain
function. While the behavioral part of this relationship is well
described, the interpretation of the sources of the rhythms is
at variance with accepted views.
The first point to make is that the EEG rhythms in both the
archi- and neocortex are likely to be the result of rhythmic
inputs which originate in pacemaking areas; the lateral tha-
lamic nuclear complex in the case of the neocortex (Andersen
& Andersson 1968) and the medial septum in the case of the
hippocampus (Petsehe, Stumpf & Gogolak 1962). The
evidence for the pacemaking role of the lateral thalamic
nuclei consists of their rhythmic activity, which persists after
ablation of the neocortex, and the suppression of rhythmic
activity in the neocortex after ablation of the lateral thalamus.
In the hippocampus, the essential role of the septum in the
generation of hippocampal RSA is also well established.
However, this rhythmic activity may require feedback from
the hippocampus through the fimbria (McLennan & Miller
1976), although septal pacemaking burst activity can still be
observed in the absence of hippocampal RSA under certain
conditions, such as that produced by LSD (Stumpf, Petsehe &
Gogolak 1962) or during the electrical silence following
hippocampal seizures (Petsehe et al. 1962). The role of the
pacemaker area in regulating the EEG implies that behav-
ioral or pharmacological factors which alter the EEG are
likely to exert their effect on the pacemaker nuclei and not on
the cortex via the reticulo-cortical system, as suggested by
V&R.
In accordance with this view, evidence for the subcortical
location of the cholinergic link which modulates the EEG in
Type 2 behavior is extensive. With one exception, early
investigators observed drug effects on the EEG following
systemic or intracarotid administration of drugs. The one
exception, Miller, Stavraky & Woonton (1940), applied eser-
ine directly to the cortex and observed EEG desynchroniza-
tion. This was accompanied by twitching of muscles and
vibrissae, indicating that the local application may have
produced a generalized arousal which was reflected in the
EEG. Furthermore, when atropine was applied directly to the
cortex of locally anesthetized, curarized cats, it failed to
synchronize the EEG, even though it clearly reached an
effective concentration within the cortex because it enhanced
the release of acetylcholine from the area of application
(Szerb 1964). Yet atropine synchronized the EEG when given
i.v. in this preparation.
Although hippocampal feedback to the septum may be
necessary for the generation of hippocampal RSA, recent
evidence indicates that the septo-hippocampal cholinergic
tract is not responsible for the generation of the atropine-
sensitive RSA (Dudar, Whishaw & Szerb 1979). In freely
moving rats, both sensory stimulation and motor activity
increase the release of acetylcholine from the hippocampus,
although only sensory RSA is "cholinergic," according to
V&R. Systemic atropine abolishes the increase in acetylcho-
line release due to sensory stimulation but not that due to
running. Therefore, both the RSA and the increased septohip-
pocampal cholinergic activity induced by sensory stimulation
reaches the septum through a pathway containing a choliner-
gic link. On the other hand, motor activity activates the
septum through a different pathway, which lacks cholinergic
synapses. Furthermore, since both "cholinergic" and "non-
cholinergic" RSA is accompanied by increased cholinergic
activity in the hippocampus, these terms are misleading.
V&R refer to the "ascending cholinergic reticular forma-
tion" of Shute & Lewis to explain the effect of atropine on the
EEG. However, this concept is now somewhat outdated due
to the nonspecific distribution of cholinesterase, which was
used as a marker for cholinergic neurons by Shute & Lewis.
With more sophisticated methods, the origin of the choliner-
gic afferents to the neocortex have now been identified in the
n. basalis magnocellularis located in the ventral pallidum
(Emson & Lindvall 1979; Lehmann, Nagy, Atmadja &
Fibiger 1980). These cholinergic neurons are clearly not
identical with the thalamocortical neurons responsible for
modulating the EEG. Furthermore, the cholinergic input to
the cortex may be activated independently of the EEG (Szerb
1967). Therefore, the corticopetal cholinergic neurons do not
appear to be the ones that mediate the synchronizing effect of
atropine. A much more likely site for the action of atropine is
the cholinoceptive units in the n. reticularis thalami (Ben-Ari,
Dingledine, Kanazawa and Kelly 1976), which are inhibited
by acetylcholine through muscarinic receptors. These neurons
have a well-documented inhibitory projection to the ventro-
basal complex of the thalamus and probably receive choliner-
gic input from the mesencephalic reticular formation. Thus,
during Type 2 behavior, activation of the cholinergic tract
from the mesencephalon causes a disinhibition of the thala-
mocortical neurons in the ventrobasal thalamus, leading to a
desynchronized EEG. This disinhibition is readily blocked by
atropine acting on the cholinoceptive units in the n. reticularis
thalami. During Type 1 behavior, activation of a noncholiner-
gic pathway may lead to a disinhibition of the same thalamo-
cortical projection.
In summary, the difference in the susceptibility of EEG
activation to atropine during Type 1 and Type 2 behaviors is
probably due to different tracts being activated in the dien-
cephalon and not due to differences in the tracts projecting
directly to the archi- and neocortex.
An atropine-sensitive and a less
atropine-sensitive system
Robert P. Vertes
Department of Physiology, University of Michigan, Medical School, Ann
Arbor, Mich. 48109
As one who is actively engaged in research investigating the
role of the brainstem in the control of the forebrain, I do not
find the distinction between atropine-sensitive and atropine-
resistant RSA and LVFA (see Glossary in target article)
extremely useful. I go on record here as a fan of Vanderwolf's
early hypothesis that in the behaving rat RSA (theta) is
correlated with Type 1 behaviors and irregular nonrhythmic
hippocampal activity is associated with Type 2 behaviors. I
admit to a great deal of difficulty with the new two-system
theory, especially with respect to the species that I am most
familiar with, the rat. One significant problem I see is that
according to Vanderwolf & Robinson (V&R), rats, unlike
other species such as rabbits, manifest only one type of RSA
(the atropine-resistant kind) rather than two types during
waking behavior. The absence of any behavioral manifesta-
tion of atropine-sensitive RSA in the rat would suggest that in
this species, at least, the atropine-sensitive system is of little
importance during behavior.
LVFA. V&R propose that there are two forms of LVFA
during behavior and REM sleep in the rat. However, no
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 493
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
electrophysiological criteria are presented by which the two
types of LVFA can be distinquished. In contrast, the criteria
for separating the two types of RSA are clearly stated, i.e.,
atropine-sensitive RSA is slow (5-6 Hz) and atropine-resistant
is fast (7-12 Hz). The absence of similar criteria for LVFA
would suggest that under natural conditions of waking and
REM sleep the cortical EEG does not significantly differ
during either Type 1 and 2 behaviors or during phasic vs.
nonphasic periods of REM. In this respect, the situation does
not appear radically changed from the classical association of
LVFA with alert waking behavior and REM sleep.
RSA during active (REM) sleep. It was stated that during
REM sleep there are two naturally occurring forms of RSA,
the slow (6 Hz) atropine-sensitive type associated with
nonphasic events and the fast (>6 Hz) atropine-resistant type
correlated with the phasic events of REM. My experience
does not substantiate this distinction. I do not find that RSA is
predominantly at 6 Hz during nonphasic REM but rather that
it varies between 6-9 Hz, which is the same frequency
normally present in the waking rat during Type 1 behaviors.
In agreement with V&R, I do observe that during periods of
very intense phasic activity during REM, RSA frequency
increases to 9-10 Hz. This, however, appears no different
from similar conditions during waking in which RSA can
increase in frequency during vigorous movements.
In summary, I see no evidence that in the rat under natural
conditions (waking behavior and REM sleep) the hippocam-
pal RSA or cortical LVFA can be differentiated into two
types on the basis of electrophysiological criteria. As a result I
am not convinced that for the rat, at least, there are two forms
of RSA or LVFA. I would acknowledge that the situation may
be entirely different in other species. As an alternative, I
would propose that there is a single RSA (LVFA) system that
is atropine-sensitive and depends upon the integrity of the
brainstem-septal-hippocampal axis for its expression. It was
pointed out that the atropine-sensitive system could only be
disrupted by very large doses of atropine (25 mg/kg, ip, in
the rat). Several explanations for why this might be the case
were provided, i.e., large doses must be given to extensively
occupy the muscarinic cholinergic receptors; atropine does
not penetrate the brain well; and normal RSA patterns can
persist with only a very small fraction of the RSA-generating
system intact. I believe that each of these explanations is very
reasonable. I would, however, go one step further and suggest
that possibly even with these exceptionally large doses of
atropine the ACh-mediated RSA (LVFA) system is partially
but not completely blocked. I would propose that in the
presence of large doses of atropine, RSA could be generated if
an ascending ACh system were highly activated. V&R
supported their claim for an atropine-resistant system by the
demonstration that RSA can be generated in the atropinized
rat during Type 1 behaviors and during the phasic events of
REM. An equally possible explanation for this phenomenon
could be that during Type 1 behaviors and phasic REM the
reticular formation is intensely active and capable of driving
some cholinergic RSA-generating sites in the forebrain not
completely saturated with atropine. The one-system theory
would be supported by the finding that (1) anatomically
distinct atropine-sensitive and atropine-resistant systems
could not be identified in brainstem stimulation studies (Rob-
inson & Vanderwolf 1978 and Vertes 1980); (2) discrete
reticular and hypothalamic lesions were incapable of selec-
tively eliminating the atropine-sensitive or atropine-resistant
system (Robinson & Wishaw 1974) and (3) the search for a
transmitter for the atropine-resistant system has been largely
unsuccessful. One obvious test of this hypothesis would be to
inject doses of atropine well in excess of those necessary to
disrupt the atropine sensitive RSA. This may prove to be
futile, however, because it may be impossible to completely
saturate ACh receptors at any dose of atropine.
494 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
In conclusion, I believe that the results supporting the
hypothesis of two RSA (LVFA) systems could be explained by
proposing a single ACh system with some components that
are disrupted by atropine at 25 mg/kg and others which are
only affected at doses greater than 25 mg/kg - a highly
atropine-sensitive and a less atropine-sensitive system, if you
will.
Independent forebrain and brainstem
controls for arousal and sleep
Jaime R. Villablanca
Mental Retardation Research Center and Departments of Psychiatry and
Anatomy, School of Medicine, University of California, Los Angeles, Calif.
90024
The main goals of the Vanderwolf & Robinson (V&R) article
are: (1) To disqualify the reticular formation (RF) theory of
arousal; (2) To propose a new role for the "reticulo-cortical
systems." The themes of my commentary will be that the first
purpose is only apparently accomplished and that the authors
do not really offer any substantial original view to replace the
theory. In addition, I will criticize the concept of the RF as
the brain "center" for arousal but, still arguing that the theory
is essentially sound, I will propose that the RF is only a
portion of a more complex activating-deactivating system of
the brain.
V&R use two clusters of arguments: (a) The lack, under
many conditions, of correlation between EEG neocortical
desynchrony and behavioral wakefulness (W) or between
EEG synchrony and behavioral sleep (S); (b) The fact that
sleep-waking (S-W) as well as a variety of other behaviors are
still seen in decorticate and decerebrate animals. Regarding
the EEG-behavioral "dissociation" in their examples, there is
a body of experimental data which, I believe, offers an
adequate explanation for these apparent paradoxes. This
information will be briefly summarized.
In a series of studies (Villablanca 1962, 1965, 1966b, 1966c;
Olmstead & Villablanca 1977) we demonstrated that the
forebrain of the cat, entirely separated from the brainstem by
a permanent, complete transection of the mesencephalon, i.e.,
the isolated forebrain, shows the following:
(a) Sustained periods of EEG low-voltage, fast-wave
desynchronized rhythms which, as in the intact animal,
alternate with periods of sustained high-voltage, slow-wave
synchronized patterns. These events are even seen after
premesencephalic transection.
(b) EEG desynchrony and synchrony in the isolated fore-
brain are functionally equivalent to similar EEG patterns
observed during W and S, respectively, in the intact animals
because (i) the EEG of both patterns in the neocortex and
hippocampus is comparable to those during W and S of intact
cats; (ii) in animals with mesencephalic transections caudal to
the third nerve nuclei, pupillary diameter and ocular move-
ments follow well the fluctuations of the EEG; (iii) the EEG
synchrony can be interrupted by olfactory stimulation, and
this arousal is accompanied by mydriasis.
(c) The effectiveness of an olfactory stimulus for arousing
the sleeping isolated forebrain depends on the duration of the
EEG synchrony prior to the stimulus onset. This graded
character of the arousal response suggests a variable tonus of
an active S mechanism.
(d) Where additional visual and olfactory deafferentations
are carried out the S-W alternation persists.
(e) The theta rhythm is the predominant EEG pattern of
the hippocampus. Assuming that theta represents a moderate
level of hippocampal activity (Kemp & Kaada 1975; Parmeg-
 Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
giani et al. 1967), we have hypothesized that a moderate level
of arousal is the dominant state of the isolated forebrain.
(f) The S-W patterns of the isolated forebrain are usually
dissociated from those of the decerebrate animal, i.e., the
animal itself can be sleeping while the forebrain displays
waking activity and vice versa.
(g) The drugs tested in the isolated forebrain, including
atropine and eserine, produce EEG patterns identical to those
seen in the intact brain.
(h) In preliminary experiments in kittens, we have
observed that the EEG and behavioral patterns of the isolated
forebrain develop approximately normally even though the
mesencephalic transection is done at a time of immaturity of
the EEG (10 days of age); this ontogenetic independence
further documents the importance of the forebrain processes.
Most of these observations have now been replicated by at
least nine laboratories around the world in cats (Batsel 1964,
Belardetti et al. 1977; Naneishvili et al. 1975a, Serkov et al.
1966; Slosarska & Zernicki 1973; Sterman 1972), dogs (Batsel
I960), rats (Gottesmann et al. 1980), and monkeys (Massopust
et al. 1968). In the monkey, waking EEG rhythms are present
immediately after transection, whereas in cats, depending on
the lesion technique, (Olmstead & Villablanca 1977; Villa-
blanca 1972) there may be a delay of days (which was the
effect that gave rise to the erroneous deafferentation theory
of sleep following Bremer's (1937) experiments). This fits
with the demonstration that the more rostral mesencephalo-
diencephalic components of the RF are more important in
primates (Bricolo 19/5; Mogoun 1954; Rossi 1980). Thus, the
relatively protracted course of recovery of arousal in the cat
may be interpreted as a neurological shock which tends to
disappear with encephalization.
In another series of reports we demonstrated that cats
without the telencephalon (Villablanca & Marcus 1972) or
even decerebrate animals (Villablanca 1966a) can S or W and
display a variety of related behaviors. The concomitant
polygraphic events also were defined. These findings have
also been replicated (Houston & Borbely 1974; Jouvet 1962;
Sterman 1972) and have been reviewed extensively (Moruzzi
1972, 1974; Villablanca 1974).
An important conclusion from these data is that the fore-
brain possesses intrinsic systems for the control of S and W
which can function independently of brainstem influences.
Similar capabilities are also present in the lower brainstem
separated from descending forebrain controls. A dual system
for both arousal and S, one in the forebrain and the other in
the brainstem, can therefore be postulated. Moruzzi (1972,
1974) has critically reviewed our findings, and additional
evidence, reaching conclusions similar to ours. The multiple
areas demonstrated to be involved in the control of W and S
in both segments of the encephalon provide ample structural
and functional bases for these systems (see Belardette et al.
1977; Brodal 1969; Moruzzi 1972; Dement & Villablanca
1974; and other recent reviews).
We have further hypothesized that the rostral system may
be uncoupled from brainstem mechanisms either physiologi-
cally or by pathological and pharmacological events (Villa-
blanca, 1966 a,c). Therefore, considering this potential of the
two areas for independently displaying intrinsic behavioral
and EEG manifestations of S and W, the "dissociations"
mentioned by V&R can be incorporated into the RF theory.
For example, in an intact individual REM sleep and cataplexy
may be conceived, respectively, as resulting from a physiolog-
ical "disconnection" in which the rostral brain is awake
enough to be aware of the contents of dreams (REM sleep) or
is fully awake, with normal awareness (cataplexy), but with
both states occurring in a "deactivated," sleeping, brainstem
and body. Conversely, somnambulism may be understood as
a state in which the forebrain remains asleep, as evidenced by
the synchronized EEG and lack of awareness (Kales et al.
1974), while the brainstem and body are awake, thereby
accounting for the erect posture and locomotion. In patholog-
ical conditions, a number of etiologies could anatomically
uncouple the rostral from the caudal S-W mechanisms,
thereby creating, depending on the topography as well as the
time course of the process, a variety of EEG-behavior combi-
nations in the rostral brain versus independent combinations
in the brainstem and body (Bricolo 1975; see Harner &
Naquet 1971).
Another phenomenon which apparently conflicts with the
RF theory is the presence of synchronized EEG activities in
the neocortex of awake, performing animals. Those activities
are not generalized over the entire cortex but consist of
specific EEG spindle-like events occurring in discrete regions
which are associated with the display of well-defined behav-
iors. Concomitantly, rhythmic field potentials or single unit
activities occur in the corresponding thalamic nuclei (Rou-
geul-Buser et al. 1978). A reasonable interpretation is that
these "focal rhythms" represent the replacement of EEG
desynchrony of arousal by synchronized oscillations of excit-
ability within a given thalamocortical channel, with the
consequence that they "prevent normal sensory or sensory-
motor processing in that particular thalamocortical channel"
(Buser 1980). Thus, the presence of the rhythms does not
contradict the RF theory but would indicate selective deacti-
vation of only portions of a thalamocortical system.
It has been shown that atropine and eserine can produce
electrocortical effects similar to those seen with the same
doses in intact animals when injected systemically in prepara-
tions with an isolated forebrain (Villablanca 1966), or with
the cortex totally disconnected from subcortical influences
(see Villablanca 1966c; Villablanca 1966/1967), or following
topical application (see Longo 1971). Furthermore, within a
certain range of atropine dosage, external (see Villablanca
1966c) or RF stimulation (Bradley 1968) can still desynchro-
nize the EEG such that at relatively low doses the dissociation
is either partial or nonexistent. These data offer an alternative
explanation for the well-known EEG-behavioral dissociation
produced by these drugs. Indeed, treating the neocortex as an
effector for the desynchronizing actions of the RF one can
propose that adequate doses of atropine or eserine can effec-
tively block the cortical circuitry, thus rendering it insensitive
to the RF physiological inputs. Similar local effects have been
described for other drugs (see Longo 1971 and Villablanca et
al. 1970) such that ignoring this basic phenomenon is one of
the pitfalls in interpreting effects of drugs in S-W physiology
and in EEG control.
I do not see how the presence of S-W in decorticate or
decerebrate animals contradicts the RF theory. Although
V&R call it the "reticulo-cortical" theory, there is no doubt
that the core component is the RF. The forebrain structures
are important as long as they are there to be "awakened" or
enabled by the arousal action to process information and
produce outputs. Since the RF is essentially intact in decorti-
cate cats, it should not surprise anyone that such animals can
display features of W and S to the extent permitted by the
CNS areas still available. Indeed, in order to validate V&R's
viewpoint it would be necessary to show that eliminating the
RF in the decorticate animal does not impair waking. But this
does not seem to be the case. For example, in acute thalamic
cats we demonstrated that following a mesencephalic transec-
tion the thalamic EEG spindles and interspindle lulls are
replaced by almost continuous high voltage, slow-wave activ-
ity (Villablanca & Schlag 1968). Indeed, one would predict
that destruction of the RF in decorticate or decerebrate
animals would result in a total abolition of the W state.
The above certainly does not mean that the neocortex or
striatum do not play a role in the control of S-W. We
(Villablanca & Marcus 1972; Villablanca et al. 1976) as well as
others (Jouvet 1962; Moruzzi 1972) have extensively discussed
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 495
Commentary/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
their role and I refer the reader to those papers. Moreover, I
have proposed (Dement & Villablanca 1974) that the overall
brain organization for S- and W-control follows a Jacksonian
pattern, and I have defined specific roles for the main CNS
"levels" involved. This hypothesis includes the notion that the
deterioration of both S and W manifestations increases as a
lesion progresses from the "highest" to the "lowest" control
"levels" and matches well with our concept of a dual system
for CNS activation-deactivation.
I have great difficulty in seeing that V&R clearly establish
any new function for their two pharmacologically distinct RF
subsystems. Indeed, these projections may still be conceived
as having a role compatible with the broad functional concept
of the RF theory, i.e., ascending influences which enable their
target areas to carry on their specific functions through the
activating process which we call arousal. The lengthy discus-
sion of the neurotransmitter involved is of little help since,
regardless of synaptic mechanisms, the key issue is still the
functional role of the RF. Furthermore, in the attempt to
show a new role for these subsystems, V&R's emphasis is on
the functions of the target areas, i.e., the cortices. Or, at best,
they fail to convince one that the subsystems' role differs from
that of the corresponding projection areas. Adding to my
hesitation are the perplexing final remarks that "there are, as
yet no clear behavioral criteria by which Type 1 or Type 2
behavior can be classified" and that the specific roles of their
reticulo-cortical pathways "is a topic for future research."
In conclusion, I feel that we are not being presented with
any robust innovative theory. As an alternative, I propose the
concepts of independent forebrain-brainstem systems for
arousal and S, and that their organization is Jacksonian. These
ideas establish an integrative framework for an overdue
theoretical "new synthesis" which: (i) incorporates informa-
tion collected after the reticular theory was proposed; (ii)
rejects the notion of CNS "centers" for the control of S and W
and precludes the interpretation of S as merely a reduction of
RF activity; and (iii) effectively explains most spontaneous
events as well as experimental and pathological phenomena
related to W-S, including those discussed by V&R.
ACKNOWLEDGMENT
This work was supported by USPHS Grants HD-05958 and HD-
04612.
Behaviorism and voluntarism
O. S. Vinogradova
Institute of Biophysics of the USSR Academy of Sciences, Puschino-
on-Oka 142 292, Moscow District, U.S.S.R.
The progress of science is immense. The "behavioristic" or
"ethological approach" proposed by Vanderwolf & Robinson
(V&R) allows us to understand electrophysiological and even
biochemical events through their temporal coincidence with
behavior (movements).
V&R's approach is based on the assumption that even such
events as arousal should be regarded as "inferred processes,"
as are perception, attention, motivation, memory and so on;
thus they should be rejected by the true investigator of
behavior. But, strangely enough, the most "inferential,"
psychological, and even philosophical concept of all - voli-
tion - is not only allowed into the behavioristic box (otherwise
so well sterilized against psychological germs), but is even
used as basic differentia specified in the analysis provided by
the authors. Aside from the basic inconsistency of such an
approach from the behavioristic point of view, three argu-
ments invalidate it.
First of all, it is a sweet, but deceptive dream, that any
496 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
brain state, reflected in EEG changes, must be immediately
translatable into easily interpretable overt movements for the
benefit of an experimenter. While I am sitting immobile,
gnawing my pen, according to V&R, I am in state II, and
synchronization reigns in my neocortex. But I am vigorously
thinking about V&R's paper, and I am certain that my
neocortex is desynchronized. (This allusion to myself is justi-
fied by the fact that animal experimental data in the paper
sandwiched between introduction and conclusion are slightly
peppered with human EEG data; this suggests that the
proposed ideas are applicable to humans as well.) Although
animals do not read papers, it is, alas, conceivable, that there
are states (hormonal influences, inner sensations, etc.) which
may exert strong influence on brain activity levels (and thus
on the EEG) without immediately observable manifestations
in behavior.
The second pitfall seems to be obvious to the authors
themselves. It is the absence of reliable criteria for differen-
tiating voluntary movements from automatic ones by means
of simple observation. After it is multiply stated that hippo-
campal theta and cortical desynchronization occur "if, and
only if voluntary behavior is being performed," we learn that
"there are, as yet, no clear behavioral criteria by which Type
1 or Type 2 behavior can be classified." The automatic
behavior is "defined as behavior with no consistent relations
to RSA." Indeed, "it often seems as though "voluntary" and
"automated" are defined post hoc by the correlation of
hippocampal EEG patterns with a response," as Black,
another advocate of the proposed view, wrote in 1975 (p.
154). Thus, first theta is proclaimed to be a correlate of
voluntary behavior; then voluntary behavior is defined as
behavior during which theta is present, and automatic behav-
ior as behavior during which theta is absent. I regard this as a
brilliant example of circulus viciosus in logic.
Third, and maybe most important, is the problem of what
is correlated with theta and desynchronization in voluntary
movements (if we consider such a possibility for a moment.)
From my early scientific youth I was taught by the late Prof.
A. R. Luria that there is nothing more complex than volun-
tary action. It includes the perception and analysis of the
environment (under certain levels of arousal and attention),
proper motivation, decision making, the planning of action,
its execution, feedback information, and the evaluation of the
result obtained. The complex composition of voluntary action
has also been demonstrated by Anokhin, Pribram, and many
others. From V&R we learn that his major finding is that RSA
is not correlated with environmental circumstances or
psychological processes, but only with overt behavior. What
does this mean? Are the movements per se so different during
voluntary and automatic behaviors? What is the difference
between, for instance, turning the head to attend to a stimulus
and turning the head to lick the skin? What happens with
learned (voluntary) movements, such as lever pressing, after
prolonged practice, when they cease to be accompanied by
theta?
As a result of V&R's proposed principles of analysis, we are
confronted with such surprising types of "voluntary behav-
ior" as forced running in the treadmill, immobilization under
curare, and muscle twitches during paradoxical sleep, since
all these states correlate with high-frequency theta. The
example of curarization is used by the authors to show that
proprioceptive impulses, which are provided by the move-
ment, are not necessary for the production of theta. In fact,
V&R show only that movement itself is not necessary for
theta production. The intrinsic similarity between forced
running and the curarized state may reside in the fact that
both are stressful situations with high level of arousal, evoked
by strong and unusual bodily sensations. As for paradoxical
sleep, it has repeatedly been shown by neurophysiological
methods that this state is in fact in many respects equivalent
 Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
to the state of high activity (arousal) of the forebrain. As
Morrison stated recently, ". . . paradoxical sleep can be
viewed as a period during which the CNS acts as if there were
a continual influx of unexpected, or novel, stimuli" (Morrison
1979, p. 572).
In speaking about movement (walking, running, rearing),
we should remember that this provides an animal with a high
inflow of sensory information. The environment, sliding by
during the movement, is the source of rapidly changing visual
information, of acoustic stimuli with shifting characteristics;
movement itself produces a strong inflow of somatosensory
and proprioceptive impulses. It is a scholastic undertaking to
attempt to segregate "pure motor" and "pure sensory"
components in the behaving animal [See also Lynch: "The
Functional Organization of Posterior Parietal Association
Cortex" BBS 3(4) 1980.] For the "ethological" behaviorist it is
also advisable to take into account the fact that small animals
(mice, rats) have narrow visual angles; hence, in order to
perceive and analyse their environment - to orient and
perform adaptive behavior in it - these animals must move
around in this environment much more than do larger
animals.
Thus, it seems that the classical theory of reticulo-cortical
relations has greater potential for explaining various facts,
and much less contradictions, than the "new synthesis."
Many objections against the classical theory of reticulo-
cortical interaction listed by V&R have long ago found their
explanations; some of these objections are just wrong (for
example, the interpretation of the state of the pretrigeminal
animal as "deep coma," just because it cannot move, for
obvious reasons; the prolonged active (aroused) state of the
forebrain in this preparation is demonstrated and well docu-
mented).
But there is one more specific question regarding the
various theta frequency bands. One band, according to V&R,
is of low frequency and cholinergic pharmacologically; the
other is high frequency and its pharmacological nature is first
proclaimed unknown ("Two types of RSA," para. 13) but
later declared "trace aminergic," whatever that may mean.
There are many investigations, both old and new, which show
that stimulating one and the same point in the reticular
formation can produce theta in its full range of frequencies. It
has been shown, moreover, that theta frequency changes as a
linear function of the intensity of reticular stimulation
(Stumpf 1965). Both the frequency of burst discharges and
the number of rhythmically bursting septal cells also grad-
ually increase. Thus, are we indeed dealing with two
different processes, or with a continuum of frequencies,
which may be regarded as measures of the levels of afferent
input from the reticular formation?
Some relevant data have been obtained in our experiments
with deafferented septum (Vinogradova et al. 1980). It was
shown, that in the basally undercut rabbit septum, completely
deprived of MFB (medial forebrain bundle) influences, a
relatively large proportion of the septal units (22%) preserve
the ability to discharge in extremely regular rhythmic bursts,
with a mean frequency of 3.3 per sec. Very low frequency
theta was found to be present in the hippocampal EEG of
these animals. The rhythmic burst activity was also observed
in slices of guinea pig septum, incubated in vitro (burst
frequency was 2-3 per sec). In both conditions the application
of physostigmine (i.v. or in the bath medium) increased the
proportion of rhythmically bursting cells and the density of
their bursts, and slightly shifted their frequency (by 1-2 per
sec) into the higher range. Thus, we conclude that septal
neurons possess the intrinsic ability to produce very low
frequency rhythmic bursts which can only be slightly acceler-
ated by influences on the septum's own cholinergic mecha-
nism. To further accelerate this intrinsic rhythmic mecha-
nism, ascending brainstem influences are necessary. It is very
probable that this basic septal rhythmic mechanism is more
resistent to anaesthetics, which are known to suppress activity
of the reticular formation. In the normal state the basic
frequency of the septal pacemaker is always a little higher
than in the deafferented septum (not less than 4 per sec in the
rabbit), due to the influences of the reticular formation. Any
increased level of excitation of the reticular units is recoded
into accelerated bursts of septal units, and thus into higher
frequency hippocampal EEG theta.
In conclusion, I wish to express my sincere regret that after
so much work done by V&R we have not learned anything
about the mysterious functions of the hippocampus (which
certainly does not participate in triggering the movements, as
both human and animal lesion data show), or about the
functional significance of theta in the machinery of the brain.
The proposed "new synthesis" only proves once more that "to
correlate is not necessarily to elucidate an axiom that is most
apparent in RSA research" (Klemm 1976, p. 23). It certainly
does not shake the classical theory of arousal. The voluntaris-
tic attempt to substitute, for neurophysiological realities,
vague descriptions based on purely subjective observations
and interpretations, seems outdated and fruitless as a contri-
bution to our understanding of brain and behavioral prob-
lems.
Authors' Response
Brain-behavioral studies: The importance of
staying close to the data
C. H. Vanderwolf and T. E. Robinson"
'Department of Psychology, University of Western Ontario, London, Ontar-
io, Canada N6A 5C2and"Neuroscience Laboratory, University of Michigan,
Ann Arbor, Mich. 48109
For the convenience of the reader, we have summa-
rized our discussion of the commentaries in Table 1.
On the left side of the table are the issues raised; on the
right side the commentaries that raised points relevant
to the issue.
Mind and behavior. A very general point raised by a
number of commentators (Bennett, Carlson, Eichen-
baum, Ranck) concerns the basic aims and definition
of brain-behavior research. Should our main aim be to
discover physiological correlates of psychological
processes or should we try to understand the neural
mechanisms that control behavior (i.e., movement and
posture)? It has been pointed out that even if one's long
range goal is the elucidation of psychological processes,
some form of behaviorism is a logical necessity (Ratliff
1962). Mind, regarded as the mechanism that controls
behavior, is not accessible to direct examination, appar-
ently not even in oneself (Hebb 1980). Consequently,
mind can be studied only indirectly, as an inference
from behavior. If this is so, we would do well to study
behavior very thoroughly, regardless of our philosophi-
cal preconceptions. This conclusion is also suggested by
the view that the brain is chiefly a device for regulating
motor output (Sperry 1952). Careful study of motor
output might, therefore, provide clues to the functional
organization of the brain.
Psychological theories tend to relegate behavior to
the role of a gauge or indicator of mental activity
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 497
Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior

Table 1. A guide to replies by Vanderwolf and Robinson to

It is possible that atropine-sensitive RSA and LVFA
specific commentators
(see glossary in target article) play some role in the
stimulus control of adaptive behavior, as we suggest.
However, adequate methods for the electrophysiologi-
Section Commentators cal study of this role have not yet been applied in a
behavioral experiment. It is not possible to conclude, as
1. Mind and behavior Bennett, Buzsaki et al., Carl- Bennett does, that atropine-sensitive RSA is directly
son Eichenbaum, Ranck related to attention or cognitive processes since this
2. Voluntary and automatic Bennett, Buzsaki et al., theory is directly contradicted by the well-known
behaviors Eichenbaum, Malmo & experiments of A. H. Black (1975, see also "A reply to
Malmo, Villablanca,
Vinogradova
Vinogradova" below) which Bennett failed to
3. EEG activation as a corre- Buzsaki et al., Eichenbaum, mention.
late of arousal Jasper, Jones, Ranck, Rou-
geul et al., Somjen, Steriade, Voluntary and automatic behaviors. A number of
Sutherland et al., Villablan- authors (Bennett, Buzsaki et al., Eichenbaum, Malmo
ca, Vinogradova & Malmo, and Vinogradova) have referred to our use
4. Two types of RSA and Buzsaki et al., Eichenbaum, of the term "voluntary." The target article discusses a
LVFA Komisaruk, Malmo & Mal- large number of empirical observations which show
mo, Shiromani & Fishbein,
that certain motor activities are consistently accompan-
Vertes, Vinogradova
5. Characteristics of as- Krnjevic, Phillis, Shiromani & ied by distinctive patterns of brain activity while other
cending cholinergic sys- Fishbein, Szerb & Dudar, motor activities and behavioral immobility are gener-
tems Villablanca ally not accompanied by these patterns. These groups
6. Behavior and unit activity Malmo & Malmo, Steriade of motor activities require names. Initially, we chose
7. Possible influences on Calloway, Carlson, Eichen- the terms "voluntary" and "automatic" since: (1) One
brain-behavior research baum, Komisaruk, Malmo & of the groups of motor activities (voluntary) comprises
Malmo, Ranck such behaviors as locomotion and lever pressing which
8. Interpretation of lesion ex- Somjen, Sutherland et al. are familiar as operant or instrumental responses. (2)
periments The other group of motor activites (automatic)
9. A reply to Hirschman Hirschman comprises more reflexive or consummatory behaviors
10. A reply to Vinogradova Vinogradova
such as the startle response, licking and chewing. (3)
The terms voluntary and automatic, used in this way,
are consistent with the usage of J. Hughlings Jackson
(Hebb 1980). Consequently, the psychological ap- (see Taylor 1958), who was an important innovator in
proach has neglected the careful observation and the brain-behavior field. The need to name the behav-
description of behavior, as Lorenz (1973) and ior patterns is equally well served by the terms Type 1
Tinbergen (1963), among others, have pointed out. As and Type 2, although these clearly have less heuristic
an example of this in the brain-behavior field, it is value.
possible that mentalistic preconceptions have delayed In retrospect, using the term "voluntary" may have
by several decades the appearance of accurate descrip- been an error in public relations. For many people
tions of the relation between hippocampal and neocor- "voluntary" has strong metaphysical connotations and
tical slow-wave activity and behavior. is not acceptable simply as a means of referring to a
Consequently, it seems to us that there has not been group of behaviors. For this reason we preferred using
much progress since the beginnings (historically speak- the terms "Type 1" and "Type 2" behavior in the
ing) of scientific investigation of the relation of target article.
mammalian brain activity to behavior. Quite simply, Villablanca and Malmo & Malmo are puzzled by
since behavior was not regarded as a topic of particular our statement that "there are, as yet, no clear behav-
interest, it was not studied adequately in much of the ioral criteria by which Type 1 or Type 2 behavior can
early work. Ranck makes this point very effectively in be classified." Obviously, there is no great difficulty in
his discussion of the necessity of providing a behavioral distinguishing, for example, among walking, face-
definition of arousal. Buzsaki, Isaacson & Hannigan, washing, and immobility. Therefore, at a practical
Eichenbaum, Komisaruk, and Malmo & Malmo also level, it is easy to distinguish Type 1 from Type 2
favor more accurate description of overt behavior. behavior. The difficulty comes in determining whether
The study of cognitive processes in relation to brain there is anything in comon (other than distinctive
activity, recommended by Bennett and by Eichen- patterns of brain electrical activity) among the various
baum, has usually involved testing in rather complex Type 1 behaviors which is not shared by Type 2
situations (in mazes, in discrimination apparatus, or behaviors. A number of characteristics which Type 1
under various reinforcement schedules in a lever box). behaviors may have in common are discussed in the
The stimuli controlling behavior are often not target article (also see Vanderwolf, 1971; and O'Keefe
adequately known and behavior may be described only & Nadel 1978).
in terms of "correct responses," "errors," or "rate of In reply to Buzsaki et al., we are not concerned with
responding" on a lever. Reports based on such studies whether or not we adhere in a dogmatic manner to the
are often uninterpretable (Arnolds et al. 1979c; doctrines of either B. F. Skinner or the Lorenz-
Whishaw & Vanderwolf 1973) since essential informa- Tinbergen school of behavior study, although we do
tion is not included. acknowledge our indebtedness to these behavioral

498 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4

 Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
Table 2. Models of reticulo-cortical activity and behavior
Model 1: Traditional arousal
theory
Ascending reticiilar acti- EEG arousal (LVFA, RSA);
vating system Behavioral waking.
Model 2: Vanderwolf and
Robinson theory
a) Cholinergic reticulo- Atropine-sensitive LVFA
cortical system
and RSA; Stimulus con-
trol of Type 1 and Type
2 behavior?
b) Noncholinergic reticu- Atropine-resistant LVFA
lo-cortical system and RSA; control of
Type 1 behavior?
c) Descending reticulo- Behavioral waking.
spinal system (plus
other descending
systems)
investigators. What we do claim is that we have
provided a more accurate descriptive account of the
relations between brain slow-wave activity and behav-
ior than was previously available. It may well be that at
some level in the brain there is "a great difference
between a foreleg movement in stepping toward a
receptive female and a similar movement made away
from a predator" but distinctions of this type do not
seem to be reflected by differences in reticulo-cortical
activity.
EEG activation as a correlate of arousal. Table 2
provides a simplified summary of traditional arousal
theory and of our proposed replacement for it.
A number of commentators (Eichenbaum, Jasper,
Jones, Rougeul, Bouyer & Buser, Somjen, Steriade,
Villablanca, and Vinogradova) question our conclu-
sion that the conventional arousal theory of reticulo-
cortical cortical activity is inadequate and should be
abandoned. Rougeul et al. and Villablanca suggest that
the presence of slow-wave activity during Type 2
behavior in the normal waking animal is compatible
with conventional arousal theory since the slow waves
do not occur everywhere and LVFA persists in some
cortical areas. This is true. However, LVFA also occurs
in stages I and 2 of normal sleep (Dement & Mitler
1974) and there is undoubtedly a great deal of similar-
ity between the EEG activity of a cat standing up
drinking milk from a saucer and that of a cat lying
down in an early stage of sleep. When this is considered
together with the other findings mentioned in the
target article (paradoxical sleep, LVFA during anes-
thesia and coma, effects of muscarinic blocking drugs)
it seems to us that the conclusion that EEG activation
correlates poorly with the state of arousal is a simple
statement of fact. Ranck provides additional evidence
in support of this conclusion.
Rougeul et al. also state that synchronized patterns
occurring in the waking state do not contradict conven-
tional arousal theory since such wave patterns are
"completely distinct from slow sleep activities." It is
true that some of the slow wave rhythms occurring in
the waking state have a morphology distinct from those
occurring during quiet sleep, but this is not true in all
cases. For example, Marczynski et al. (1968, p. 236)
state that "The bursts of PRS (post-reinforcement
synchronization, i.e., slow waves occurring in a cat
while drinking) were not discernible from spindle sleep
ECG (electrocorticogram) recorded from the same
cortical region."
In any case, conventional arousal theory has always
emphasized the difference between "synchrony" and
"desynchrony" and has paid scant attention to the
various patterns which large amplitude slow waves can
assume. For example, a cerveau isole preparation
(Bremer 1935; Moruzzi 1972) displays very rhythmic
slow waves which are certainly not identical with the
patterns occurring during quiet sleep. Yet no one, to
our knowledge, has ever objected that this makes the
cerveau isole preparation irrelevant to the physiology
of sleep! Consequently, an appeal to the particular
properties of various types of slow waves cannot
provide a basis for a defense of conventional arousal
theory.
Rougeul et al. suggest that more research should be
devoted to the study of the various patterns of wave
morphology and location which neocortical slow-wave
activity can assume. We agree with this wholehearted-
ly. However, it is necessary to point out that we shall
learn very little about the behavioral significance of
such rhythms unless adequate behavioral techniques
are used in conjunction with electrophysiological stud-
ies. Rougeul et al. are mistaken in their remark that it is
only in the hippocampus that we are concerned about
the correct placement of recording electrodes. In fact,
as Fig. 4 (of the target article) shows, we emphasize the
importance of proper electrode location in the record-
ing of electrical activity in the neocortex as well as in
the hippocampus.
With respect to wave morphology, it should also be
mentioned that Somjen is mistaken in his statement
that the slow waves produced by atropinic drugs are
different from those observed during natural sleep.
Montplaisir (1975) reports that neocortical slow-wave
activity produced by scopolamine in restrained
monkeys is very similar to the slow-wave activity
present during natural sleep. In addition, interval histo-
grams of neocortical unit activity following scopol-
amine treatment closely resembled those obtained
during natural sleep. Our own data indicate that
waking atropinized rats engaged in Type 2 behavior
display large slow waves (2-6 Hz) and spindles (10-16
Hz) which closely resemble the activity present during
natural quiet sleep in the same individual animals
(Vanderwolf 1975). However, since LVFA appears
during Type 1 behavior in atropinized rats, the slow
waves and spindles are frequently interrupted. Casual
examination of such records may be responsible for the
widespread but false impression that atropine does not
reproduce the electrographic phenomena of slow-wave
sleep.
Another point which should be made is that conven-
tional arousal theory attempts to relate all ascending
reticulo-cortical activity to a single behavioral dimen-
sion extending from deep coma to extreme excitement.
If, as we show, there are at least two distinct ascending
reticulo-cortical systems with different relations to
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 499
Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
behavior, then this simple concept must be false on
logical grounds alone.
A number of other points are raised by the commen-
tators in defense of conventional arousal theory. It
seems to us that some confusion results from the use of
such words as "conscious," "waking," "alert," or "vigi-
lant" to refer to two quite different things: (1) the
presence of a waking posture (standing up, head held
up against gravity, eyes open, etc.) plus spontaneous
movement, and (2) an inferred psychological state. For
example, Steriade states that "decorticate rats may
display head movements, walking, and rearing, but I
assume that waking processes transcend this reper-
toire." Nonetheless, since the psychological state is not
susceptible to direct measurement, most sleep research-
ers have been content to define the waking state in
terms of criterion #1 or even simpler measures such as
the electro-myogram or electro-oculogram. Let us
follow this sensible convention and use the term "wak-
ing behavior" to refer to meaning #1 above.
Waking behavior is not dependent on ascending
reticulo-cortical activity, as is shown by the effects of
decortication. Thus, we can reject Somjen's theory that
waking behavior survives in atropinized animals
because some cortical neurons are unaffected by atro-
pine. However, although atropinized or decorticate
animals are undoubtedly capable of waking behavior,
there is also no doubt that adaptive behavior is severely
impaired in such animals (i.e., there are impairments in
feeding, sexual behavior, performance in mazes, etc.)
Jasper is mistaken in his statement that we do not take
this into account. In fact, the behavioral effects of
antimuscarinic drugs provide an important basis for
our suggestion that the ascending cholinergic reticular
formation plays a role in the stimulus control of behav-
ior (see "Synthesis" section below). One might go on to
infer that the alterations in behavior produced by
decortication or atropinization are due to an impair-
ment of "consciousness" in sense #2 above. However,
taking this step leads one inevitably into the quagmire
of psychological speculation. Is it possible that the
behavioral effects of atropine are not due to impair-
ment of "alertness," as Jasper suggests, but are instead
the result of impairment in perception, motivation,
attention, learning, memory, recall, or intelligence?
Questions of this type are, for all practical purposes,
insoluble. This is due, in part, to the impossibility of
defining exactly what the psychological terms mean. It
is simpler to stay close to the facts. Decorticate or
atropinized animals are capable of waking behavior (in
sense #1 above) but the organization of behavior is
abnormal. Detailed observation of a wide variety of
behaviors under various circumstances should lead to a
comprehensive description of these abnormalities
(Schallert et al. 1980; Vanderwolf, Kolb & Cooley
1978). The behavioral abnormalities should then be
interpreted in terms of measurable neural events and
not in terms of hypothetical psychological processes. As
an example, one might suggest (without engaging in
psychological theorizing of any kind) that the poor
performance of an atropinized rat in a maze test is due
primarily to the blockade of a cholinergic reticulo-
cortical pathway. This suggestion may or may not be
correct, but it does have a relatively clear meaning.
500 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
Using present-day techniques, it could be shown to be
either incorrect or probably correct. It is much less
clear what is meant by statements to the effect that
atropine alters maze performance by interfering with
one or more of: alertness, learning, memory, recall,
attention, motivation, drive, etc.
An incidental point which can be mentioned here is
that Buzsaki et al. are mistaken in their statement that
we failed to observe changes in grooming behavior in
decorticate rats. Such changes were documented quan-
titatively by Vanderwolf, Kolb & Cooley (1978).
Villablanca suggests that the forebrain and lower
brainstem possess potentially independent mechanisms
for sleep and waking which normally operate as a
harmonious system but can be dissociated by transect-
ing the brainstem and in other ways. It is very interest-
ing that the neural machinery for generating LVFA
and RSA is intact in the isolated forebrain. One
wonders whether these rhythms are totally atropine-
sensitive or not. Atropine-resistant inputs might origi-
nate in the lower brainstem and be severed by a rostral
brainstem transection.
A separate question, also raised by Villablanca, is
whether the presence or absence of LVFA or RSA in
the isolated forebrain can be taken as evidence of
waking or sleep in either a behavioral or a psychologi-
cal sense. We think that such conclusions would be
unjustified since cerebral electrographic patterns are
not reliable indices of sleep, waking, or consciousness in
the intact animal. For example, we do not attribute
"wakefulness" or "consciousness" to an etherized
animal under light surgical anesthesia simply on the
basis of LVFA in the electrocorticogram.
Villablanca's theory encounters other difficulties.
For example, contrary to Villablanca's suggestion,
investigations by Jouvet (1972; 1974), Pompeiano
(1967), Siegel (1979), Vertes (1979), and others
(reviewed in target article) show that the brainstem is
not "deactivated" during active (REM) sleep. In fact,
the entire brain seems to be very active but skeletal
motor activity is suppressed by inhibition at a spinal
level. Although Villablanca's theory seems to suggest
that the behavior of a high decerebrate human would
be approximately equivalent to the behavior of a sleep
walker with an intact brain, this is improbable. Sleep
walkers can walk about and avoid obstacles, but it is
doubtful that decerebrate humans would be capable of
this.
Finally, contrary to the suggestion of Villablanca,
we do not claim that the entire reticular formation is
irrelevant to waking behavior. The target article states
specifically that descending reticular fibers are of
importance in this but that ascending fibers are not.
Unfortunately, surgical lesions or electrical stimulation
of the reticular formation do not provide a means of
affecting one or another of these sets of fibers in a
selective manner, as Sutherland, Whishaw & Kolb
point out.
We agree with Jones that conventional arousal
theory is anachronistic and oversimplified, but it is
certainly no straw man, as is shown by the fact that a
number of commentators defend it vigorously. The
approach which Jones proposes to refurbish arousal
theory is to identify constellations of correlated physio-
 Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
logical and behavioral events which can then be
labelled as "sleep," "waking," etc. Manipulations such
as drugs or brain lesions give rise to new constellations,
for which (presumably) new names could be invented.
It seems to us that this approach loses sight of the main
aim of brain-behavior research, which is to give an
adequate account of behavior in terms of the activity of
the nervous system. We must aim at a causal analysis
and not content ourselves merely with naming clusters
of correlations. Logically then, we must begin with a
description of behavior which can, subsequently, be
accounted for in terms of nervous activity. (This
consideration does not, of course, dictate research strat-
egy. For example, it might be useful to begin with a
brain eVent, then look to behavior to determine its
functional significance.)
Jones is certainly right in her contention that patho-
logical conditions, such as atropinization, do not tell us
how brain activity is correlated with behavior in
normal animals. However, experimental manipulations
do provide data relevant to a causal analysis. For
example, the effect of atropine shows that LVFA is not
essential for the occurrence of waking behavior, as
Wikler (1952) pointed out many years ago. To state, as
Jones does, that "Waking, which is normally character-
ized by low amplitude electrocortical activity is no
longer normal waking when this activity increases in
amplitude with alropine" is meaningless in the absence
of a behavioral definition of waking. As Ranck puts it,
"Arousal, or something like it, deserves a clear behav-
ioral definition independent of neural correlates, other-
wise the correlation (between arousal and neural activi-
ty) cannot be tested."
Jones's statement that reticulotelencephalic systems
are necessary for behavioral arousal appears to be
incorrect. Mesencephalic (Woods 1964) and thalamic
(Wang & Akert 1962) animals which lack a telencepha-
lon are often intensely active and "aroused." If lesions
restricted to the brainstem reticular formation abolish
"behavioral arousal" then one must conclude that the
lesions have damaged something (e.g., reticulospinal
fibers) in addition to the ascending projections to the
telencephalon.
Both Steriade and Vinogradova have objected to
our reference to Batini et al. (1959) in relation to the
evidence for the presence of LVFA during coma. We
included this reference since Loeb et al. (1959)
mention that comatose human patients who display
normal EEC. activity are often found to have damage
to the lower brainstem, including the pons. Since the
pretrigeminal cat preparation is at least partly similar
to this (and helps to explain the clinical phenomenon)
we included the reference. However, the point was not
discussed adequately, and these commentators are
justified in their objections.
Two types of RSA and LVFA. The commentaries by
Eichenbaum and Komisaruk reveal some misunder-
standing of the relations of hippocampal activity to
behavior which we hope to clarify. While we agree
with Komisaruk (Malmo & Malnio also refer to this)
that there is a degree of arbitrariness in classifying RSA
and LIA by inspection from oscillograph records, we
do not think there is any ambiguity in our criteria for
RSA. The record of an immobile rat shown in the
upper left corner of Fig. 3 is not claimed to be an RSA
pattern. We would consider it to be an LIA pattern,
even though it undoubtedly contains some power in the
5-7 Hz frequency band. The main point is that the
record becomes decidely more rhythmic when the
animal walks and can also assume a highly rhythmic
pattern during ether anesthesia (Fig. 3, lower left). It
may be worth pointing out that RSA cannot be equated
simply with activity in a particular frequency band.
Factors such as rhythmicity and amplitude must also
be considered. For example, hippocampal spikes
contain frequencies that overlap with the upper range
of RSA frequencies. Nonetheless, the spikes can be
distinguished from RSA quite easily on the basis of
amplitude and overall morphology. Hippocampal
spikes and RSA also differ in terms of pharmacology
and relations to behavior.
Clear RSA patterns ordinarily do not occur during
waking Type 2 behavior in a normal rat. However,
RSA (atropine sensitive) can be induced during Type 2
behavior by such agents as electrical stimulation of the
reticular formation, various drugs (including ether),
brain lesions, and prolonged training in learning tasks
involving painful electric shock. Since either LIA or
RSA patterns can occur during Type 2 behavior, we
have never claimed (contrary to Eichenbaum's state-
ment) that Type 2 behavior is a "correlate of slow-
RSA," but merely that such RSA "sometimes accom-
panies waking immobility or other Type 2 behavior."
According to Vanderwolf (1975, p. 300) "One input to
both hippocampus and neocortex is blocked by atro-
pine and stimulated by eserine and is essentially unre-
lated to concurrent motor activity."
An additional point which should be mentioned is
that the pattern we have referred to as LIA is not
identical in all conditions. Records such as those in Fig.
3 suggest that a normal, waking, motionless rat displays
somewhat more 5-7 Hz activity in its LIA pattern than
a motionless atropinized rat or a normal rat in slow-
wave sleep. This impression has recently been
confirmed by a power spectral analysis of hippocampal
activity in normal and atropinized rats by Leung,
Lopes da Silva, and Wadman (Leung, personal
communication). It may be that a low level of activity
is present in ascending cholinergic reticulo-
hippocampal pathways in a waking, motionless rat.
This results in greater power in the 5-7 Hz frequency
band than is present during quiet sleep or in a motion-
less atropinized rat. Under some circumstances,
ascending cholinergic activity becomes sufficiently
intense to produce a clear (atropine-sensitive) RSA
pattern. Thus, Komisaruk's view that the difference
between "theta and nontheta activity may be quantita-
tive rather than qualitative" is partially correct.
However, a qualitatively distinct factor appears to be
introduced during Type 1 behavior, such as walking,
when a noncholinergic input produces RSA. Vertes,
Vinogradova, and Shiromani & Fishbein do not agree
with the latter statement. They propose instead that
there is only one reticulo-hippocampal pathway which
produces RSA and that this pathway is cholinergic.
Thus, Vinogradova, Brazhnik, Karanov, & Zhadina
(1980) propose that low frequency RSA in anesthetized
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 501
Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
animals is due to an intraseptal generator which oscil-
lates at a low frequency when the reticular formation is
depressed as result of the anesthetic. This RSA is
sensitive to atropine. In the waking state, ascending
reticular activity drives the generator at a higher
frequency, producing the higher frequency RSA
observed during Type 1 behavior. This simple explana-
tion is inadequate since, as pointed out in the target
article, the RSA which accompanies Type 1 motor
activity in the waking state is resistant to atropinic
drugs and to hemicholinium. Vertes attempts to
circumvent this difficulty by assuming that ascending
cholinergic reticular activity is particularly intense
during Type 1 behavior and might therefore be more
difficult to block with atropine. In this case, larger
doses of atropine might be more effective. However,
Vanderwolf (1975) mentions that atropine SO4 in doses
of 100 mg/kg does not block the RSA accompanying
Type 1 behavior and even doses of 150 mg/kg are
ineffective (unpublished experiments). A dose of about
25 mg/kg is sufficient to abolish any RSA occurring
during waking Type 2 behavior or during anesthesia.
Moreover, Vertes s hypothesis cannot account for the
selective effect of hemicholinium, a drug which pre-
vents the synthesis of brain acetylcholine by blocking
the high affinity uptake of choline by cholinergic
neurons. If the RSA accompanying Type 1 behavior is
dependent on high levels of activity in ascending
cholinergic neurons, it should be especially sensitive to
the effect of hemicholinium, since acetylcholine stores
would be rapidly exhausted (Rommelspacher & Kuhar
1974). The low levels of ascending cholinergic reticular
activity invoked to account for the RSA occurring in
anesthetized animals should make such RSA relatively
resistant to the drug, according to Vertes s hypothesis.
In fact, the reverse is found. The RSA accompanying
Type 1 behavior is unaffected by intraventricular
injections of hemolinium while the RSA occurring in
urethane anesthetized animals is abolished (Robinson &
Green 1980). Consequently, we think it is necessary to
postulate the existence of two distinct RSA-generating
inputs to the hippocampus, although, as Vertes points
out, our information concerning these systems is rather
limited.
An important clue to the understanding of the
atropine-resistant input to the hippocampus (which we
neglected to mention in the target article) is that large
hypothalamic lesions abolish atropine-resistant RSA, if
only temporarily, but "release" atropine-sensitive RSA
so that it occurs more readily than in a normal animal
(De Ryck & Teitelbaum 1978; Kolb & Whishaw 1977;
Whishaw & Kolb 1979). Stimulation of the hypothala-
mus produces atropine-resitant RSA and vigorous Type
1 motor activity (Bland & Vanderwolf 1972; Kramis et
al. 1975). Therefore, ascending atropine-resistant
inputs to the hippocampus may arise in or pass through
the hypothalamus.
In relation to the comments of Buzsaki et al., Vertes,
and Vinogradova, it must be pointed out that although
atropine-sensitive RSA usually has a frequency of
about 4-7 Hz and atropine-resistant RSA usually has a
frequency of 7-12 Hz, frequency in itself is not an
infallible predictor of the response of a given RSA
pattern to atropinic drugs. Thus, stimulation of the
502 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
midbrain reticular formation in a waking rat produces
an atropine-sensitive RSA of 8-10 Hz during behavioral
immobility. On the other hand, small doses of pento-
barbital reduce the frequency of RSA accompanying
climbing behavior (Type 1) to a value below 7 Hz but
the RSA retains its resistance to atropine nonetheless. In
general, it is true that the RSA accompanying Type 1
behavior is atropine-resistant while any RSA occurring
during waking Type 2 behavior or anesthesia is atro-
pine-sensitive, regardless of the frequency of the RSA
(Kramis et al. 1975; Vanderwolf 1975).
Vertes raises the further question of the significance
of atropine-sensitive RSA in rats, since ordinarily these
animals do not display clear RSA independent of
behaviors such as walking or head movement (Type 1)
in the waking state. One situation in which we claim
normal rats display 5-7 Hz RSA with immobility is
during the nonphasic intervals of an episode of active
sleep. Vertes does not find predominantly low
frequency RSA at this time, although it has been
reported by a number of other authors (Robinson et al.
1977; Soulairac et al. 1965; Usui & Iwahara. 1977;
Whishaw & Vanderwolf. 1973). Vertes's failure to find
a clear difference in RSA frequency between phasic
and nonphasic periods in active sleep might possibly be
due to the use of an insensitive method for monitoring
phasic activity. The descending phasic excitatory
barrages onto motor neurons during active sleep affect
a wide variety of muscle groups (e.g., limbs, trunk,
vibrissae, eyes) but all muscles are not active during
every phasic episode. Consequently, if monitoring is
not extensive, some phasic events might be missed and
the associated hippocampal activity might be incor-
rectly classified as belonging to a nonphasic period.
Robinson et al. (1977) used vibrissal EMG, a movement
sensor, and close visual observation to determine when
phasic episodes occurred. Nonphasic episodes were
defined as periods when all three measures failed to
detect activity at a time at least 1 sec before or after a
recorded phasic episode. Phasic episodes were defined
as periods of motor activity lasting 1 sec or more. With
these definitions, 6-7 Hz RSA was observed during
nonphasic periods but RSA of 8 Hz or more was
observed during phasic periods. Robinson et al. (1977)
also showed that the RSA correlated with phasic events
is atropine-resistant while nonphasic RSA was atropine-
sensitive. Consequently, active sleep is an example of a
normal physiological condition in which rats generate
atropine-sensitive RSA.
Whether atropine-sensitive RSA occurs in rats under
normal conditions in the waking state is less certain.
After prolonged shock avoidance training, low-
frequency RSA occurs during immobility in animals
that have not been subjected to drug treatment of
surgical intervention beyond the implantation or
recording electrodes. Such RSA is atropine-sensitive
(Vanderwolf 1969, 1975; Whishaw 1972). It is also
possible that a cholinergic input to the hippocampus is
active concurrently with a noncholinergic input during
Type 1 behavior (Leung & Vanderwolf 1980). This
hypothesis is supported by the finding of Dudar,
Whishaw & Szerb (1979) that high levels of acetylcho-
line release occur in the hippocampus in rats during
locomotion in a treadmill.
 Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
Finally, Vertes suggests that LVFA, as well as RSA,
is controlled by a single ascending cholinergic reticular
system. The evidence which we have to support the
concept of two distinct inputs to the neocortex which
are independently capable of producing LVFA, is
similar to the evidence supporting the concept of two
inputs to the hippocampus. Essentially, the LVFA
correlated with Type 1 behavior is pharmacologically
distinct from the LVFA which often occurs during
Type 2 behavior. However, we note that neocortical
evoked potentials vary iivrelation to hippocampal RSA
and Type 1 behavior in rats (Racine, Tuff & Zaide
1975; Schwartzbaum & Kreinick 1973). Consequently,
there may be electrophysiological criteria by which
atropine-sensitive and atropine-resistant LVFA can be
distinguished without the use of drugs.
Characteristics of ascending cholinergic systems. In
reply to the points raised by Szerb & Dudar, we did not
mean to imply that atropine necessarily exerts all of its
effects on slow-wave activity by a direct action on the
neocortex or hippocampus. In fact, we specifically
mentioned the possibility that subcortical cholinergic
synapses may play a role in the production of atropine-
sensitive RSA. However, this topic should have been
discussed more extensively and we thank Szerb &
Dudar for doing this. Similarly, we thank Krnjevic and
Phillis for providing additional insights into the mech-
anisms by which ascending cholinergic systems affect
hippocampal and neocortical activity.
We think that the sites at which atropine acts to
abolish one form of neocortical LVFA and hippocam-
pal RSA have not been adequately identified. There
are many indications that acetylcholine normally
influences hippocampal and neocortical neurons, as the
target article and several of the commentaries point
out. (Consequently, one might think that atropine exerts
its effects on slow-wave activity by a direct action in
the neocortex and hippocampus. Thus, Villablanca
refers to a study (Villablanca 1966/1967) showing that
atropine increases slow-wave activity, while eserine
decreases it, in a cerebral hemisphere isolated from the
thalamus. In opposition to this, Szerb (1964) showed
that topically applied atropine increases the efflux of
acetylcholine from the neocortex but does not produce
slow waves. However, acetylcholine efflux from the
cortex may originate from more than one source (corti-
cal cholinergic afferents and intracortical cholinergic
neurons). Therefore, it seems possible than an
increased acetylcholine efflux might appear when atro-
pine is applied topically even though deeply situated
cholinergic synapses remain unblocked. Such synapses
might be sufficient to permit the persistence of LVFA.
Kxperiments of the type discussed by Shiromani &
Fishbein suggest that systemically administered cho-
linergic agonists or antagonists might affect cortical
activity and behavior by actions at a number of sites. It
is obvious that there is a great deal remaining to be
learned.
We note in passing that Shiromani & Fishbein are
mistaken in claiming that Lewis et al. (1980) found a
high concentration of muscarinic receptor sites in the
pontine reticular formation. Lewis et al. do not
mention the pontine reticular formation specifically,
but in a later paper they, and others, show that pontine
reticular nuclei, such as the nucleus pontis oralis or
nucleus pontis caudalis, contain low levels of musca-
rinic receptors (Rotter, Birdsall, Field & Raisman 1979;
Wamsley, Lewis, Young & Kuhar 1981).
Behavior and unit activity. As pointed out by Malmo &
Malmo we omitted many studies on the relation of
reticular unit activity to behavior, although it is not
true that we referred only to Vertes (1979). Our aim
was to confine the review primarily to reticulo-cortical
inputs involved in EEG activation.
However, studies on the behavioral relations of retic-
ular formation cells have been reviewed recently by
Siegel (1979a, 1979b) as we pointed out. Siegel reviews
studies which have related unit or multi-unit activity in
the reticular formation to a wide variety of processes.
These include: sensory processes, pain, conditioning,
habituation, arousal, complex behavioral states, active
sleep, eye movements, respiration, locomotion, and
specific movements. Siegel shows that different func-
tions have been ascribed to the same units by different
investigators. Consequently, many of these functions
may have something in common. What is this common
factor? Arousal level might be such a common factor,
and many investigators have related reticular forma-
tion unit activity to arousal, as Malmo & Malmo and
Siegel point out. However, others have stressed the lack
of a correlation between reticular unit activity and
arousal. For example, in a study of multi-unit activity
in the mesencephalic reticular formation and thalamus,
Goodman & Mann (1967) concluded that activity levels
were sometimes as high during anesthesia as in the
waking state. It would be interesting to know whether
the electrophysiological phenomena Steriade describes
as occurring during waking LVFA might not also occur
during LVFA periods in etherized animals. That is, are
the single unit phenomena related to "arousal" level, as
Steriade suggests, or are they related to an EEG wave-
form independent of "arousal" level?
From his studies in cats, Siegel (1979a) has suggested
that the activity of most cells located in the medial
reticular core is actually correlated with the activity of
specific muscle groups. Vertes (1979) has reported
similar findings in rats. In rats many reticular forma-
tion units increase their rate of firing during specific
behaviors and active sleep (phasic MOV-REM cells).
Vertes (1979) also described tonic MOV-REM cells
which increase their firing rate during active sleep or
whenever a Type 1 behavior occurs. Although Malmo
& Malmo suggest that the activity of these cells, "was
not specific to the kind of movement," it is specific in
the sense that their activity is highly correlated with
Type 1, but not Type 2 behaviors (Vertes, personal
communication). Others have reported similar rela-
tions to behavior using multi-unit recording techniques
(Malmo & Malmo 1977; Schwartzbaum 1975).
In agreement with the conclusions drawn in the
target article, the foregoing studies show that the
activity of many reticular formation units is related to
specific aspects of overt behavior and not to arousal in
the traditional global sense. We suggest that some cells
(e.g., Vertes's [1979] tonic MOV-REM cells) may be
involved in the activation of the hippocampus or the
THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4 503
Response/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
neocortex while others have primarily descending
axons and are directly involved in specific movements.
No doubt many additional types of units will be found
as well.
Malmo & Malmo also suggested that our conclusions
about the relations of atropine-resistant neocortical and
hippocampal slow-wave activity to ongoing motor
behavior would be strengthened if other recording
techniques yielded similar results. Although we did not
review such studies extensively, many investigators
have reported similar correlations using different tech-
niques. Ranck (Ranck 1973; Feder & Ranck 1973) was
the first to relate hippocampal unit activity to ongoing
motor behavior. One class of cells (Ranck's theta cells)
is reported to show exactly the same relations to behav-
ior as hippocampal RSA. More recently, O'Keefe and
others (O'Keefe & Nadel 1978) have described the
same behavioral relations at the single-unit level,
although cells which fire in close relation to Type 1
movements are given different names by different
investigators (e.g., Ranck's "theta cell" is O'Keefe's
"displace cell"). Although many "nontheta" hippo-
campal cells do not fire in relation to motor activity,
some do fire in relation to specific movements, or to
movements which occur in a particular place (O'Keefe
& Nadel 1978; Ranck 1973). In addition to hippocam-
pal slow-wave and unit activity, hippocampal evoked
potentials also vary as a function of motor activity
(Leung 1980; Winson & Abzug 1978). This is also true
of some types of evoked potentials in the neocortex, as
was mentioned above (Racine, Tuff & Zaide 1975;
Schwartzbaum & Kreinick 1973). [See also O'Keefe &
Nadel: "The Hippocampus as a Cognitive Map" BBS
2(4) 1979.]
Malmo & Malmo refer to a hypothesis of Teitel-
baum (1976), which assumes that atropine-sensitive
and atropine-resistant RSA might be related selectively
to the CA1 and dentate RSA generators. This is incor-
rect, since both types of RSA are present in both
generators (Whishaw et al. 1976).
Possible influences on brain-behavior research. Ways
in which our analysis of reticulo-cortical activity in
relation to behavior might be applied to other topics in
the broad field of behavioral research are suggested by
Calloway and by Carlson. Naturally, we welcome this
development. However, we would caution against any
uncritical acceptance of Type 1 and Type 2 behaviors
as totally distinct groups. We agree entirely with
Sutherland et al. that our synthesis does not go very far
in providing an account of how the brain controls
behavior. Type 2 behaviors, in particular, are unlikely
to be a homogeneous class. We think that the most
general lesson which can be derived from our experi-
ence is that brain-behavior research requires an induc-
tive approach involving extensive observation and
description of behavior as well as brain activity. As
Banck points out, our methods have been extremely
simple, involving little more than visual inspection of
both behavior and brain electrical activity. Initially this
was justified, since the possibilities of simple observa-
tion had not been adequately explored. When a good
observational basis has been laid, we hope that analyti-
504 THE BEHAVIORAL AND BRAIN SCIENCES (1981), 4
cal techniques can be more successfully applied to the
analysis of both brain activity and behavior.
A final point that may be worth mentioning is that a
large number of processes are simultaneously active
during any natural behavior. If one wishes to study
sniffing in relation to RSA for example, as recom-
mended by Eichenbaum and by Komisaruk, it would
be a mistake to restrict one's observations to the pattern
of respiration, ignoring head movements, stepping, etc.
Respiration entrains itself readily to the occurrence of
ongoing movement patterns (Wilke, Lansing & Rogers
1975). Therefore, it is possible that an apparent
entrainment of sniffing to RSA may be a consequence
of a more fundamental entrainment of head-move-
ment to RSA. This would be missed if head-movement
were not monitored accurately, perhaps using the
device recommended by Malmo & Malmo (Mundl &
Malmo, 1979). In general, if one restricts one's observa-
tions unnecessarily, incorrect conclusions are likely to
result.
Interpretation of lesion experiments. While reticulo-
cortical projections are not essential for sleep and
waking when the entire cerebral cortex is removed,
Sutherland et al. state, it is nonetheless possible that a
selective lesion of ascending reticulo-cortical fibres
would produce an impairment of sleep or waking. We
agree. However, it is worth pointing out that if a
particular brain lesion results in the disappearance of
some function, one cannot conclude that the damaged
structures are essential to the function in question. It is
always possible that neurons in some other area, which
are essential to the function, are depressed or inhibited
as a result of the lesion. However, if some function
survives despite the presence of a large lesion, one can
conclude that none of the neurons which were
destroyed are essential to that function. [See also
Denenberg: "Hemispheric Laterality in Animals and
the Effects of Early Experience" BBS 4(1) 1981.]
Therefore, it appears that there are no neural elements
in the cerebral cortex (including the elements that
generate the EEG) which are essential for the behav-
ioral phenomena of sleep, arousal, waking, and circa-
dian rhythms. We do not dispute the fact that sleep and
waking behaviors may be altered in various ways by
decortication. However, the fact that decorticate
animals often sleep in the open without walking to a
sheltered place first suggests a deficit in the stimulus
control of locomotion rather than a deficit in the
mechanisms of sleep.
Somjen suggests that the LVFA states which we
describe may not be dependent on reticular input to
the forebrain since large lesions of the reticular forma-
tion do not produce large slow waves in the neocortex,
provided that the lesions are produced gradually rather
than suddenly. While we agree that this phenomenon is
of great interest from the point of view of recovery of
function, it is unlikely to be a reliable guide to the
function of the reticular formation under normal
conditions. The possibilities of neuronal sprouting
(Lynch & Cotman 1975) and of denervation supersen-
sitivity (Stavraky, 1961) mean that the surviving parts
of a chronically damaged nervous system may not be
functioning in the same way as they would under
 References/Vanderwolf & Robinson: Reticulo-cortical activity and behavior
normal circumstances. This difficulty does not apply to
the effects of decortication discussed above. After a
one-stage removal of the cerebral cortex, rats display
waking behavior within a few hours. Sprouting and
denervation supersensitivity presumably would not
have occurred in so short a time.
A reply to Hirschman. Two main suggestions are made
by Hirschman: (1) that hippocampal RSA is not of
biological origin, but arises as a result of movement of
the brain relative to the recording electrode, and (2)
that the presence of RSA indicates that the hippocam-
pus is inactive.
With respect to the first point, the possibility of
recording RSA both extracellularly and intracellularly
under conditions in which the mechanical stability of
the electrode in the hippocampus is sufficient for
prolonged intracellular recording (Fujita & Sato 1964)
shows that RSA can be recorded in the absence of
significant brain movement. In other words, movement
is not necessary for the occurrence of RSA. It can also
be shown that any brain movement which may occur
during spontaneous motor activity in a freely moving
animal is not sufficient to produce RSA. Thus, RSA
cannot be recorded from the rat hippocampus during
the isoelectric period following a hippocampal seizure
even though the rat walks about actively, and its brain,
presumably, continues to move to the same extent as it
does in the normal state. The same point can be made
with respect to the absence of RSA in a behaving
animal following a septal lesion. Consequently, we do
not regard movement artifacts as an important prob-
lem in recording brain activity, provided that a stable,
well-designed recording system is used. However,
there is no question but that movement artifacts can be
a tremendous problem if adequate methods are not
used.
With respect to the idea that the hippocampus is
inactive during the presence of RSA, we suggest that it
is unlikely that large brain structures function in an
"off" and "on" manner. Research must be aimed at
establishing the conditions under which various classes
of neurons are more or less active and the significance
of such activity to brain function. We note that hippo-
campal pyramidal cells are not necessarily inactive
when RSA is present (Bland, Andersen, Ganes & Sveen
1980; O'Keefe & Nadel 1978; Ranck 1975).
A reply to Vinogradova. The commentary by Vino-
gradova includes a number of points which were also
raised by other commentators and have been answered
in the preceding sections. In addition, however, Vino-
gradova's commentary contains a number of
unfounded assumptions and factual inaccuracies which
require detailed point-by-point corrections.
1. We do not state that arousal should be regarded
as an inferred process, but merely that some authors
(not all) appear to use it in this way. We recommend an
objective descriptive approach to behavior.
2. "Volition" is not discussed in the target article.
The term "voluntary" is used as a descriptive label and
does not refer to an inferred process.
3. We do not claim that "any brain state—must be
immediately translatable into easily interpretable overt
movements." Neither do we state that "synchroniza-
tion" is necessarily present during behavioral immobil-
ity or "gnawing on a pen." A large part of the target
article discusses atropine-sensitive RSA and LVFA
which, we have been at pains to show, has no immedi-
ate correlation with any type of motor activity. Vino-
gradova seems to have overlooked this completely.
4. Vinogradova is certain that her cortex is "de-
synchronized" while she thinks about our paper. In the
absence of direct evidence, we are unconvinced. It may
be that the neocortex is desynchronized much of the
time when people claim to be thinking, but we should
not forget that the presence of considerable alpha
activity (synchronization) is compatible with the
performance of a variety of intellectual tasks (Creutz-
feldt, Griinewald, Simonova & Schmiz 1967) and that
thinking or dreaming can occur during slow-wave
sleep (Foulkes 1962). Perhaps slow waves can also
occur during thinking in the waking state.
5. According to Vinogradova, perception, attention,
motivation, decision making, etc. occur during volun-
tary movement but thinking can also occur during
behavioral immobility. Most people would agree with
this. It seems to follow that if a given brain electrical
pattern is found to be consistently present during
movement and absent during the absence of move-
ment, then it must be related to the movement in some
way and not to those psychological processes which are
presumed to occur both during movement and during
immobility. An analysis based on this consideration was
used extensively by Black (1975) to show that RSA in
dogs and rats is related to motor activity rather than
inferred psychological processes. We recommend this
work to Vinogradova.
6. Contrary to Vinogradova s statement, theta (RSA)
does not necessarily disappear during prolonged prac-
tice in a lever-pressing task (Frederickson & Whishaw
1977).
7. We do not know how to evaluate Vinogradova's
statement that curarized animals are highly aroused,
but we wish to point out that curarization produces a
sharp increase in large amplitude slow-wave activity in
the neocortex (Hodes 1962).
8. The statement that mice and rats have "narrow
visual angles" puzzles us, since these animals have
almost circumferential visual fields.
9. Concerning trace amines, we recommend such
recent reviews and symposia volumes as Boulton
(1979), Mosnaim & Wolf (1978) and Usdin & Sandier
(1976).
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