Roger M. Enoka and Simon C.

Gandevia
J Appl Physiol 101:1009-1010, 2006. doi:10.1152/japplphysiol.00739.2006

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J Appl Physiol 101: 1009 –1010, 2006;
doi:10.1152/japplphysiol.00739.2006.
HIGHLIGHTED TOPIC Neural Changes Associated with Training
THE PURPOSE OF THE MINI-REVIEWS on this Highlighted Topic is to
provide a contemporary synthesis of knowledge on the changes
that occur in the physiological properties of the nervous system
in response to repeated exposure to physical training such as
exercise. The focus of the series is on the motor system, which
corresponds to those parts of the nervous system involved in
the production of movement. A key goal in this field is to
identify the adaptations that are responsible for the changes in
performance evoked by a training intervention. As indicated in
the mini-reviews, the level of inquiry on most questions is
limited to examination of associations between neural adapta-
tions and changes in performance, because it is more difficult
to identify causal relations.
Two features of this work deserve emphasis: the approaches
that are used to study the neural changes associated with training
and the methodological issues that constrain this field. One end of
the range of approaches is exemplified by work that describes a
training adaptation and subsequent studies that attempt to identify
the mechanisms responsible for the change in performance. This
approach is used by Tim Carroll and colleagues to characterize the
phenomenon known as the contralateral strength training effect,
which appears to be mediated by mechanisms that reside within
the nervous system. The performance of a strength-training pro-
gram by muscles in one limb can evoke a small strength gain in
the homologous muscles of the untrained limb. Carroll et al.
propose that the contralateral strength training effect might be
caused by either of two classes of neural mechanisms: one is
related to the spread of cortical activity to the pathways for the
contralateral limb, and the other involves adaptations in the
control system for the trained limb that can be accessed by the
contralateral limb. Although the specific mechanisms responsible
for the contralateral effect have not been identified, the adapta-
tions are likely to be distributed among cortical, subcortical, and
spinal levels. This approach provides a template for the investi-
gation of neural mechanisms that cause improvements in perfor-
mance in response to training.
The other end of the range can be characterized by studies that
examine the effects of training on the function of the nervous
system and seek to determine the mechanisms that produce the
adaptation. This approach is exemplified by studies on the effects
of exercise on cognition and dementia and is reviewed by Art
Kramer. Both observational and intervention studies indicate that
aerobic exercise can improve performance on various measures of
cognition in humans. Although these studies have produced
mixed results, meta-analyses suggest that aerobic fitness training
has a positive influence on cognition. Interestingly, the training
effects are greater when aerobic training is combined with
strength and flexibility training. Attempts to identify the respon-
sible mechanisms have involved imaging studies in humans and
invasive studies on experimental animals. The animal models
have provided evidence that voluntary exercise improves perfor-
mance on learning and memory tasks, enhances a cellular process
in learning (long-term potentiation) that upregulates molecular
factors associated with brain plasticity, and promotes growth of
new neurons and vasculature in old animals. These results indicate
that physical activity and aerobic exercise can have a positive
influence on cognition, brain function, and brain structure. Fur-
http://www. jap.org 8750-7587/06 $8.00 Copyright © 2006 the American Physiological Society
Editorial
thermore, levels of social interaction that can accompany aging
and exercise are likely to modulate this positive effect (9).
Most studies use approaches that lie along this spectrum and
tend to focus either on assessment of the adaptability of various
components of the nervous system, such as motoneurons (consid-
ered in the mini-review by Phillip Gardiner and colleagues),
motor units (Jacques Duchateau and colleagues), somatosensory
reflex pathways (Paul Zehr), and the corticospinal system
(DeAnna Adkins and colleagues), or on identification of the
constraints imposed by the nervous system on the adaptations
evoked by training (Richard Carson). These studies often do not
attempt to determine the functional consequences of a specific
adaptation. For example, Gardiner et al. describe work that fo-
cuses on molecular mechanisms that might be responsible for
changes in the biophysical properties of motoneurons in response
to exercise programs. An increase in voluntary activity can influ-
ence dendrite structure, protein synthesis, axonal transport, neu-
romuscular propagation, and other biophysical properties. These
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technically difficult studies demonstrate that motoneurons are
responsive to the demands imposed by physical activity, but they
have not yet indicated a causal relation between a cellular adap-
tation and an improvement in performance. Similarly, Zehr de-
scribes studies that found evidence of plasticity in muscle afferent
pathways in response to various training interventions. For exam-
ple, several weeks of strength training increase strength and the
amplitude of the H reflex. These studies, however, do not indicate
the relative significance of the change in a reflex pathway to the
accompanying strength gains or improvements in coordination.
Fortunately, there are some paradigms that do enable a more
direct comparison between changes in the function of the nervous
system and motor performance. For example, Van Cutsem et al.
(10) found that a training intervention with rapid, submaximal
contractions improved both the rate of torque development and
the instantaneous discharge rate of motor units. This result was
interpreted to indicate that the more rapid increase in torque after
training was attributable to an increase in the rate at which motor
units could discharge action potentials. Of course, the observation
does not indicate whether the adaptation was due either to an
increase in the intrinsic capacity of motoneurons to discharge
rapidly or to a change in the synaptic input received by the
motoneurons.
Another example of an association between changes in nervous
system function and motor performance was obtained in a study
of coordination. Carson and Riek (2) trained subjects to perform
abduction-adduction movements with the index finger to match
the increasing frequency of a pacing metronome. The improve-
ment in performance was accompanied by a change in the coor-
dination of the intrinsic and extrinsic hand muscles involved in the
task. Although the greatest changes occurred in the extrinsic
muscles, the specific adaptation varied across individuals. The
conclusion was that improved performance required learning of a
new pattern of muscle activation. This is a first step, and the
challenge is now to identify the central adaptations that drive the
change in strategy.
These examples of a neural adaptation and its contribution to a
change in performance underscore a basic tenet in science:
progress depends critically on the technology available to address
a question (5, 7). The observation by Van Cutsem et al. (10), for
1009
Editorial
1010
example, begs the question of what adaptations enabled the
motoneurons to discharge action potentials at a greater rate. The
classic approach to evaluate the potential role of changes in the
biophysical properties of the motoneurons is described in the
minireview by Gardiner et al. In this paradigm, the properties of
motoneurons in experimental animals are quantified when the
preparation is quiescent and usually anesthetized. One obvious
concern with such measurements, as emphasized by Gardiner et
al., is the relevance of the findings to the in vivo state when the
neurons are bathed in neuromodulators that can alter their function
(6). It would be preferable to determine the motoneuron properties
in the behaving state, but this technology is not yet available. In
the absence of this, an alternative strategy is to develop a com-
putational model. They provide an example of this strategy with a
model of motoneurons to estimate the changes in ionic conduc-
tances that could produce the observed changes in electrophysio-
logical properties. In general, agreement between model output
and experimental observations does not mean that the intermedi-
ate processes in the model replicate actual events (11).
Another constraint indicated by the study of Van Cutsem et al.
(10) is sample size. In most motor unit studies it is only possible
to record the behavior of a few motor units, and these differ before
and after an intervention. A common assumption in this work is
that the function of a motor unit population can be characterized
by the behavior of a few motor units. One approach, that can yield
qualitative information about motoneuronal output across differ-
ent groups of subjects is to record the discharge properties of large
samples of units during the same task (3). However, when an
intervention imposes a differential effect across the motoneuron
pool, the minimal requirement is for the study to record a suffi-
cient number of motor units to span the range of properties present
in the population. Ideally, the same motor units would be recorded
before and after the intervention. Technical capabilities limit both
prospects: spanning the range of properties and recording from the
same units.
Methodological issues in this field also involve the continual
validation of standard techniques as new methods are developed.
Two examples illustrate this point: interference electromyogram
and the Hoffmann (H) reflex. Despite decades of advising caution
in the interpretation of the interference EMG (1), it is only within
the last decade that the magnitude of the limitations has become
evident (4). Similar concerns apply to the H reflex. Although it is
incorrectly regarded as an electrical analog of the stretch reflex
(8), the readily evoked H reflex is often used as a measure of the
neural changes that can occur during training. Although some
investigators use the amplitude of the H reflex as an index of the
excitability of a motoneuron pool, this interpretation is overly
simplistic. The amplitude of the H reflex is influenced by a
number of factors, including presynaptic inhibition, disynaptic
inhibition, axonal excitability of both motor and sensory axons, as
well as the procedures used to normalize the size of the reflex (8).
Most importantly, as emphasized in the mini-review by Zehr,
reflex amplitudes vary with the functional state of the individual,
and this complicates the interpretation of the response.
Perhaps the most significant methodological limitation in this
field involves the inability to access central circuits during behav-
ior. Advances in medical imaging appear capable of providing
some new insight at this level of inquiry. As described in the
mini-review by Kramer et al., for example, functional magnetic
J Appl Physiol • VOL 101 • OCTOBER 2006 •
resonance imaging has revealed an increase in neural activity in
the frontal and parietal regions in the brain of aerobically trained
older adults during a focused attention task. Such procedures will
not reveal the cellular adaptations responsible for the changes in
coordination described in the mini-review by Carson. Instead, it
will be necessary to use the approaches described in the mini-
review by Adkins et al. to examine the cellular and molecular
events associated with changes in performance. Although it is
challenging to demonstrate a direct link between a cellular adap-
tation and a change in performance, such reductionism is neces-
sary and a hallmark of progress in science (11).
Despite the advances in field, the state of the knowledge is
rather rudimentary. Although it is possible to demonstrate neural
changes in response to a training intervention, few causal relations
have been identified. Furthermore, these relations largely involve
details about the motor output from the spinal cord, and there are
not yet links to the underlying cellular and molecular events. The
challenge is formidable, but the reviews indicate that progress is
inevitable.
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GRANTS
The authors’ work receives major support from the National Institutes of
Health (to R. M. Enoka) and the National Health and Medical Research
Council (to S. C. Gandevia).
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Roger M. Enoka
Department of Integrative Physiology
University of Colorado
Boulder, Colorado
Simon C. Gandevia
Prince of Wales Medical Research Institute and the
University of New South Wales
Sydney, New South Wales, Australia
e-mail: s.gandevia.jap@unsw.edu.au
www.jap.org