Advanced Robotics

ISSN: 0169-1864 (Print) 1568-5535 (Online) Journal homepage: http://www.tandfonline.com/loi/tadr20

Neural substrates involved in the control of

posture

Kaoru Takakusaki, Mirai Takahashi, Kazuhiro Obara & Ryosuke Chiba

To cite this article: Kaoru Takakusaki, Mirai Takahashi, Kazuhiro Obara & Ryosuke Chiba (2017)
Neural substrates involved in the control of posture, Advanced Robotics, 31:1-2, 2-23, DOI:
10.1080/01691864.2016.1252690

To link to this article: http://dx.doi.org/10.1080/01691864.2016.1252690

Published online: 06 Dec 2016.

Submit your article to this journal

Article views: 30

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at

http://www.tandfonline.com/action/journalInformation?journalCode=tadr20

Download by: [FU Berlin] Date: 05 January 2017, At: 15:44

Advanced Robotics, 2017
VOL. 31, NOS. 1–2, 2–23
http://dx.doi.org/10.1080/01691864.2016.1252690

SURVEY PAPER

Neural substrates involved in the control of posture

Kaoru Takakusaki, Mirai Takahashi, Kazuhiro Obara and Ryosuke Chiba
The Research Center for Brain Function and Medical Engineering, Asahikawa Medical University, Asahikawa, Japan

ABSTRACT ARTICLE HISTORY

This review argues neuronal mechanisms of postural control. Multi-sensory information such as Received 19 April 2016
somatosensory, visual, and vestibular sensation act on various areas of the brain so that adaptable Accepted 23 May 2016
postural control can be achieved. Automatic process of postural control, which is termed as KEYWORDS
postural reflexes including head–eye coordination accompanied by appropriate alignment of Body schema; postural
body segments, is mediated by the descending pathways from the brainstem. Cooperation of the verticality; postural
vestibulospinal, reticulospinal, and tectospinal tracts contributes to this process. On the other hand, reflex; motor programing;
walking in unfamiliar circumstance requires cognitive process of postural control, which depends anticipatory postural
on knowledge of self-body, such as body schema, sense of postural verticality, and body motion adjustment
in space. Such a bodily cognitive information is produced at the temporoparietal cortex. They are
fundamental to sustention of vertical posture and construction of motor programs. The programs
then run to execute anticipatory postural adjustment which is appropriate for achievement of goal-
directed movements. The basal ganglia and cerebellum may affect both the automatic and cognitive
processes of postural control through reciprocal connections with the brainstem and cerebral cortex,
respectively. Consequently, impairments in cognitive function in addition to damages in the motor
cortex, basal ganglia, and cerebellum may disturb appropriate postural control, resulting in falling.
Abbreviations: APA: anticipatory postural adjustment; BF: basal formation; CNF: cuneiform nucleus;
COR: cervicoocular reflex; CPGs: central pattern generators; CCR: cervicocollic reflex; DA: dopamine;
DBS: deep brain stimulation; E: extensor motoneuron; D: flexor motoneuron; FN: fastigial nuclei;
GABA: gamma aminobutyric acid; LC: locus coeruleus; LVST: lateral vestibulospinal tract; M1: primary
motor cortex; MLR: midbrain locomotor region; MVST: medial vestibulospinal tract; PD: Parkinson’s
disease; PIVC: parieto-insular vestibular cortex; PM: premotor area; PMRF: pontomedullary reticular
formation; PPN: pedunculopontine tegmental nucleus; PRF: pontine reticular formation; RD:
raphe dorsalis; RSNs: reticulospinal neurons; S1: primary sensory cortex; SC: superior colliculus;
SMA: supplementary motor area; SNc: substantia nigra pars compacta; SNr: substantia nigra pars
reticulate; VCR: vestibulocollic reflex; VOR: vestibuloocular reflex

1. Introduction process of postural control, which requires self-body

information together with spatial localization of object
Postural control is one of the innate motor functions in
in extra-personal space so that one can appropriately
animals. Particularly, the human being acquires the ability
adjust one’s posture in advance to achieve goal-directed
of standing and walking by legs and within 15 months
movements. Processing of the cognitive information by
after birth. During this developmental period, one has
the higher brain function is particularly important when
learned two aspects of postural control mechanisms: one
the subject has to learn motor skills and to behave in unfa-
is to build up upright body posture against the forces of
miliar circumstance.[1–3]
gravity, and the other is to obtain the knowledge of the
Intentional locomotor control, such as gait initia-
orientation and motion of the body in space. Here, we
tion and avoiding obstacles during walking, is skillful
define the former as the automatic process of postural
and goal-directed motor performance that requires the
control, because the subject is largely unaware the auto-
optimal response in a context involving external and
matic adjustment of postural muscle tone, maintenance
internal constraints. The external constraints are those
of upright standing, and the postural reflexes or postural
imposed by the environmental conditions under which
reactions that accompany purposeful action. On the other
the action is performed under such as the gravitational
hand, the latter mechanism is defined as the cognitive

CONTACT Kaoru Takakusaki kusaki@asahikawa-med.ac.jp

© 2016 Taylor & Francis and The Robotics Society of Japan
 ADVANCED ROBOTICS  3

forces, the reaction forces from the supporting surfaces,
imposed accelerations and obstacles. The internal con-
straints are those which originate from the body itself:
the geometrical configuration of the body segments, the
inertial characteristics of the segments, and the internal
forces associated with muscle contraction. Therefore, the
central organization of a motor skill requires motor pro-
grams which take into account all the external and internal
constraints. It requires long-term learning as the result
of which these constraints are predicted in the central
control of the motor act.[4] The predictive operations of
postural programs as well as those of precise movements
of particular body parts utilize the cerebral cortex, basal
ganglia, cerebellum, and brainstem, whose influences are
brought to bear through the descending systems acting
on the spinal cord.[4–6] The critical question is, there-
fore, how the central nervous system learns to organize
motor skills by predicting and fulfilling the external and
internal constrains. Answering to this ultimate question in
the motor control is of extreme value for neuroscientists
including clinicians and therapists so that they enable to
understand pathophysiological mechanisms and create
innovative treatment strategies of posture–gait disorders.
These knowledges are also quite available for engineers to
artificially design bipedal posture–gait models.
This review consists of two purposes. One is to
describe overview of the basic framework of the neural
mechanisms of posture control. Here, we first summa-
rize the current understanding of the core systems of the
automatic process of postural control, which is mostly
achieved by the brainstem and spinal cord. Another pur-
pose is to consider how the forebrain structures and cer-
ebellum act on the brainstem–spinal cord systems so that
cognitive process of postural control can be achieved. A
particular emphasis is placed on the importance of the
cortico–brainstem projection systems in the execution of
the higher ordered cognitive process of postural control,
such as sustention of vertical posture and anticipatory
postural adjustment (APA) for full execution of goal-­
directed movements.
2. Basic framework of the motor control
Figure 1 illustrates basic signal flows involved in motor
control. Sensory signals arising from external stimuli and/
or internal visceral information have various functions.
For example, they are to be utilized for cognitive process-
ing such as production of working memory which guides
future behavior. Alternatively, they may affect emotional
and arousal states. Sensory signals are further available

Figure 1. Basic signal flow involved in postural control.

Notes: Multisensory signals from the visual, vestibular, auditory, somatosensory, and visceral receptors act on various sites in the central nervous system. These
signals may provide cognitive and emotional references to the cerebral cortex and limbic system, respectively, so that the subject may elicit either voluntary
movements or emotional motor behavior depending on the context. In each case, automatic process of postural control, such regulation of postural muscle tone
and basic postural reflexes, by the brainstem and spinal cord is required. On the other hand, cognitive postural control is particularly important when the subject
learns motor skills and behaves in unfamiliar circumstance. See text for detail explanation.
4  K. TAKAKUSAKI ET AL.
to detect and correct postural instability by acting on the
cerebral cortex, cerebellum, and brainstem.
Accordingly, animals initiate movements depending on
either a ‘cognitive reference’ or an ‘emotional reference.’[7,8]
Voluntary movements are derived from intentionally
elicited motor commands arising from the cerebral cor-
tex to the brainstem and spinal cord. On the other hand,
emotional reference may contribute to emotional motor
behavior which is generated by the projections from the
limbic-hypothalamus to the brainstem, such as fight or
flight reactions.[8,9] Regardless of whether the initiation is
volitional or emotional, goal-directed behaviors are always
accompanied by automatic process of postural control such
as balance adjustment and regulation of postural muscle
tone. The subject is largely unaware of this process which
is evoked by sequential activations of neurons in the brain-
stem and spinal cord. However, in order to learn motor
skills or behave in unfamiliar circumstance, the subject
requires cognitive process of postural control that depends
on cognition of self-body information together with spatial
localization of object in extra-personal.
The cerebellum regulates the cognitive and automatic
processes of postural control by acting on the cerebral cor-
tex via the thalamocortical projection and on the brain-
stem, respectively. Both the feed-forward information
from the cerebral cortex and real-time sensory feedback
via the spinocerebellar tract to the cerebellum may play
major roles in these operations. The basal ganglia may also
contribute to the modulation of each process though its
GABAergic projections to the cerebral cortex and brain-
stem.[7,10,11] The degree of GABAergic influence from
the basal ganglia is regulated by the midbrain dopamin-
ergic neurons.[10–12]
3. Mechanisms of automatic process of postural
control
Quadruped animals, like cats, decerebrated at precolli-
cular-premammillary level can stand, maintain equilib-
rium, and generate postural corrections in response to
lateral tilt of the supporting platform.[13,14] Therefore,
an essential part of the mechanisms responsible for basic
postural reactions in quadrupeds is located below the
decerebration level, that is, in the brainstem, spinal cord,
and cerebellum. This section summarizes the mechanisms
of automatic process of postural control in which descend-
ing pathways from the brainstem to the spinal cord and
intraspinal neural circuitry play pivotal role.
3.1. Functional architecture of the brainstem
descending tracts
Lawrence and Kuypers [15] classified descending path-
ways to spinal cord into main two systems: the dorsolateral
and the ventromedial brainstem pathways. The dorsolat-
eral systems, which are composed of the corticospinal and
rubrospinal pathways, are involved in the control of pre-
cise limb–hand movement by acting on lateral cell groups
in the spinal cord which mainly innervate distal flexor
muscles. These two pathways descend in the contralat-
eral dorsolateral funiculus of spinal cord. On the other
hand, the ventromedial pathways are important in main-
taining balance and in postural fixation, both of which
relay especially on proximal muscles. The ventromedial
pathways are phylogenetically the oldest component of
the descending motor systems and consist of three major
tracts: the vestibulospinal, reticulospinal, and tectospinal
tracts. These pathways descend in the ipsilateral ventral
columns of the spinal cord and terminate predominantly
on interneurons and long propriospinal neurons in the
ventromedial part of the intermediate region, thus influ-
encing motoneurons that innervate axial and proximal
muscles. They also terminate directly on some moto-
neurons particularly those of the medial cell groups that
innervate axial muscles. The wide area of termination of
individual axons is important in distributing control of a
variety of functional-related motor nuclei. In the follow-
ings, role of the above descending tracts is described in
relation to the postural control.
3.1.1. Vestibulospinal tract
The vestibular system receives labyrinthine and utricle
inputs, and contributes to the generation of conjugate
eye movements, spatial orientation, and postural control
with head stability depending on gravity-based reference
frames (Figure 2(A)). The vestibular nuclei (medial, lat-
eral, and inferior nuclei) also receive proprioception and
visual sensation. The vestibular nuclei receive signals from
the cerebellum.[16,17]
The medial vestibulospinal tract (MVST) in the cat
originates from the medial and inferior vestibular nuclei
and projects as far as the mid-thoracic region via ipsilateral
ventral funiculus.[18] The MVST terminates to only axial
motoneurons. There are bilateral monosynaptic inhibition
of neck motoneurons [19] and monosynaptic excitation
of contralateral neck motoneurons.[20] This tract also has
excitatory and inhibitory connections with lower cervical
and thoracic motoneurons.[19–21] On the other hand, the
lateral vestibulospinal tract (LVST) extends ipsilaterally
throughout the length of the spinal cord and branch off
their collaterals within each segment,[22] indicating that
the LVST has the potential to influence muscles located
in different parts of the body.[23,24]
The paired otolith organs, the utricles placed approx-
imately horizontally, and the saccules vertically, respond
to linear acceleration including gravity. Their influence
leads to control neck muscles via the MVST during ori-
enting head–eye movements (vestibuloocular reflex, see
 ADVANCED ROBOTICS  5

Figure 2. Major descending pathways in the medial system.

Notes: (A) Vestibulospinal systems. The medial vestibulospinal tract originates from the medial and inferior vestibular nuclei and projects to the cervical and
mid-thoracic region via ipsilateral ventral funiculus. The lateral vestibulospinal tract extends ipsilaterally throughout the length of the spinal cord. The vestibular
nuclei receive visual, vestibular and proprioceptive sensations so that the medial and lateral vestibulospinal tracts contribute to vestibuloocular reflex and balance
control, respectively. The vestibular nuclei also receive corticofugal inputs from the vestibular cortex. This cortico-vestibular projection may contribute to sustain
vertical posture. (B) Reticulospinal systems. Neurons in the pontomedullary reticular formation which descend through the ventral and ventrolateral funiculi
constitute medial and lateral reticulospinal tracts, respectively. Reticulospinal neurons project to whole spinal segments. Therefore, the reticulospinal system
simultaneously organizes the contraction of the neck, trunk, and limb muscles so that synergistic control of postural muscle tone of whole body and postural
figure can be achieved. Flux of sensory information into the reticular formation contributes to the above process. Cortico-reticular projection arising from motor
cortical area (area 6) may be critically involved in anticipatory postural adjustment. (C) Tectospinal tract. Neurons in the superior colliculus project to upper cervical
cord and give off collaterals to the pontine gaze center in the medial reticular formation. Tectospinal tract is involved in head–eye coordination in response to
visual, auditory, and proprioceptive sensation. Cortico-collicular projection from frontal eye field (area 8) contribute to this process. See text for further explanation.

Section 3.2.1.1). On the other hand, these influences excite
ipsilateral extensor motoneurons of the limbs and trunk
and inhibit reciprocal flexor motoneurons via the LVST
(vestibulospinal reflex, see Section 3.2.1.2).
3.1.2. Reticulospinal tract
The reticular formation – the area of the medulla and
pons composed mainly of interneurons and their pro-
cesses – can best be considered as a rostral extension
of the spinal intermediate zone into the brainstem. The
reticular formation receives proprioceptive, visceral,[25]
visual,[26,27] vestibular,[25,28] and auditory [29] sensa-
tions. The reticular formation also receives inputs from the
forebrain structures (the cerebral cortex, limbic system,
and basal ganglia) and cerebellum in addition to spinal
cord.[7–11] Therefore, the reticular formation contributes
to fundamental vital activities in relation to the vigilance
state of animals via the ascending and descending projec-
tions. Ascending projections modulate cortical activities
via the thalamocortical networks.[30] Projections within
the brainstem and those descending to the spinal cord
contribute to innate motor functions such as eye move-
ments,[31–33] eye–head coordination,[34,35] oral–­
pharyngolaryngeal movements,[36–38] and control of
posture and locomotion.[39–48]
Medial and lateral reticulospinal tract arises from
the pontomedullary reticular formation (PMRF), and
descends through the ventral and ventrolateral funiculi,
respectively.[49–53] A considerable number of reticulo-
spinal neurons (RSNs) send axons through the neuraxis
from the cervical to lumbosacral segments (Figure 2(B)),
and branch off their collaterals to each segment.[51–53]
Such specific morphological features are functionally
advantageous in orchestrating synergistic contractions
of the neck, trunk, and limb musculature.
In the cat experiments, electrical stimulation applied to
the PMRF induce early (~20 ms), middle- (20–30 ms) and
late- (30–100 ms) latency responses.[54–56] Concerning
6  K. TAKAKUSAKI ET AL.
to the early latency responses, reticular stimuli pro-
duces monosynaptic excitation of the flexor and exten-
sor motoneurons of the neck, trunk, and limbs as well
as monosynaptic inhibition of neck motoneurons.[57,58]
Reticulospinal tract also has disynaptic inhibitory connec-
tions with extensor and flexor motoneurons of forelimb
and hindlimb muscles.[55,56] However, axial motoneu-
rons, especially those of the neck, are the principal targets
of the reticulospinal tract.[57,58] Because most RSNs has
a conduction velocity faster than 80 m/s, early latency
responses such as the monosynaptic and disynaptic effects
can be due to activation of fast-conducting RSNs.[59,60]
The fast-conducting RSNs may also be involved in the
activation of central pattern generators (CPGs) in spi-
nal cord to elicit locomotion.[48,61] The middle-latency
effects are mostly excitatory whose time course is similar
to those evoked by the activation of coerulospinal and
raphespinal tracts, indicating the involvement of the mon-
oaminergic systems in the middle latency effects. On the
other hand, late-latency effects are exclusively inhibitory,
which can be mediated by slow-conducting axons with
a velocity of 20–30 m/s.[54,55] The sites from which the
late-latency inhibition was evoked were widely distributed
to the dorsomedial part of the PMRF [55,56] and the lat-
eral part of the mesopontine tegmentum including the
pedunculopontine tegmental nucleus (PPN).[48,62,63]
In chronic cat preparation, reticular stimulation induced
prominent late-latency inhibitory effects on motoneurons
during rapid eye movement (REM) sleep. However, they
were completely diminished during wakefulness,[64,65]
indicating that the neuronal mechanisms of generating
late inhibitory effects are involved in the state-dependent
modulation of postural muscle tone.
3.1.3. Tectospinal tract
The tectospinal tract originates in the tectum of the
midbrain (superior colliculus [SC]), a structure that is
important for the coordinated control of head and eye
movements directed toward visual targets (eye–head coor-
dination; Figure 2(C)). Specifically, the superficial layers of
the SC receive direct retinal input, and are primarily visual
sensory in nature. They project to the visual thalamus and
pretectum, and influence visual perception. The deep lay-
ers of the SC receive information of somatosensory and
auditory sensations in addition to visual information via
the superficial layers.[66] The SC receive efferents from
the basal ganglia and cerebellum. Sensory, association,
and motor areas of the cerebral cortex provide another
major source of collicular input. For example, projections
from the visual cortex terminate superficially, while those
from the frontal eye fields (Area 8) target the deeper lay-
ers. The deeper layers provide the major projection to the
paramedian pontine reticular formation (pontine gaze
center) so that saccadic eye movements are generated.
The output from the SC also produces head turning that
associates eye movements via the tecto-reticulospinal and
tectospinal systems.[67]
3.1.4. Other descending systems
Three additional brainstem nuclei in motor function con-
tribute to the ventromedial system: the interstitial nucleus
of Cajal, the raphe nuclei (a serotonergic cell group),
and the locus coeruleus (a noradrenergic cell group).
Monoaminergic descending pathways such as the coeru-
lospinal and raphespinal tracts belong to the muscle tone
excitatory system. Because monoaminergic fibers widely
arborize in the gray matter,[68] the background excitabil-
ity of spinal neurons is increased by these tracts so that
the spinal locomotor networks sensitively respond to the
supraspinal signals and sensory afferents.
3.2. Mechanisms of postural reflexes (postural
reactions)
3.2.1. Balance control
3.2.1.1. Vestibular control of head–eye coordination.
The bony labyrinths in the inner ear contain several fluid-
filled membranous sensory end organs, which comprise
three mutually perpendicular semi-circular canals
(vertical anterior, vertical posterior, and horizontal or
lateral) and two mutually perpendicular otoliths (utricle
and saccule). This arrangement permits the most efficient
signal detection in three-dimensional space. The three
canals communicate with the otoliths. Because motion
detected by these vestibular organs is encoded in a head-
fixed frame of reference, a coordinate transformation is
thus required to encode body motion.[69]
All head movements generate vestibular signals. Most
body movements generate head movements due to the
inertial forces acting on the head atop the flexible neck.
Descending signals from higher centers also influence the
control of head and body movements through expecta-
tion of the consequences of actions. Multi-sensory signals
(vestibular, visual, auditory, and somatosensory) converge
at the vestibular nuclei, and the output of which reflects
the combination of these inputs. Loss of anyone of these
pathways to this center changes the nature of the response
to destabilization.
Vestibular and cervical reflexes stabilize the head and
neck by exciting neck muscles in opposition to head
and body movements.[70] Sugiuchi et al. [71] showed
that single MVST neurons innervated a functional set
of multiple neck muscles, and thereby implemented a
canal-dependent, head-movement synergy. Because the
medial vestibulospinal tract and reticulospinal tract have
similar innervation patterns for neck muscles, both tracts
 ADVANCED ROBOTICS  7

Figure 3. Mechanisms of vestibular reflexes.

Notes: Visual, vestibular, and proprioceptive signals converging to the vestibular nuclei contribute to vestibular reflexes, such as vestibuloocular, vestibulocollic,
and vestibulospinal reflexes. It should be noted that the cerebellum receives these sensory signals and regulates vestibular reflexes by acting vestibular nuclei and
reticular formation including the pontine gaze center. Generally, vestibular reflexes are responsible for stabilization of body equilibrium in response to eye, head,
and body movements in space. See text for detail explanation.

may control the same functional sets of neck muscles as
schematically illustrated in Figure 3.
The vestibular-neck reflex, or vestibulocollic reflex
(VCR) aligns the head with respect to the gravitational
vertical. For example, a patient leaning forward over a
walker uses this reflex to lift her head as she ambulates
so that her gaze is stabilized and oriented to the vertical
position in space. The cervicocollic reflex (CCR) aligns the
head with respect to the position of the body. The CCR
was initiated by the cervical proprioceptors via reticulo-
spinal neurons acting on cervical motoneurons; its actions
complemented those of the VCR during movement.[72] If
the body is stationary and the head moves, the VCR and
CCR work jointly to stabilize the head position. These
reflexes are particularly important in conjunction with eye
movements (Figure 3). Visual inputs which converge to
the vestibular nuclei contribute to the vestibular reflexes
in conjunction with head–eye coordination (vestibulooc-
ular reflex [VOR]). Vestibular signals together with visual
information are sent to the pontine gaze center so that
binocular eye movements are adjusted during head move-
ments (Figure 3). The vestibuloocular neurons project-
ing to the upper cervical cord where neck motoneurons
are located may also contribute to VCR.[73,74] Because
compensatory rotations of the eyes are observed during
active head movements in labyrinthine-deficient animals
8  K. TAKAKUSAKI ET AL.
[72] and in patients with absent vestibular ­function,[75]
proprioception from neck muscles may also contributes
to this process (cervicoocular reflex [COR]). It should
be mentioned that head–eye coordination also recruits
the activation of both the tectospinal and reticulospinal
systems (Figure 3). Both tracts contribute to the c­ ontrol
of eye movements and accompanying neck muscle
contractions.[34,76]
3.2.1.2. Vestibulospinal reflexes. Vestibular-bodily
interactions produced by the vestibulospinal tract
are defined as vestibulospinal reflexes (Figure 3). For
example, an activation of each semi-circular canal
results in reciprocal limb movements so that the body
is pushed into a vertical position by extending the
opposite limb.[77] On the other hand, with the head
position fixed relative to the body, an activation of
each canal compensates neck and eye movements away
from the direction of stimulation.[78] Otolith signals
from utricles and saccules also leads limb flexion and
extension patterns that restore the head to a stable
vertical position in response to horizontal or vertical
accelerations in response to gravity [79,80] with or
without vision.[81–83]
Interaction of the reticulospinal tract with vestibulo-
spinal tract plays an important role in the vestibulospinal
reflex. Because reticular formation receives input from
various sources that could influence the control of pos-
ture, including vestibular, somatosensory, cortical, and
cerebellar signals (Figure 2(B)), the reticulospinal tracts
receive inputs from the vestibular labyrinths via projec-
tions from the vestibular nuclei and cerebellum.[16,84]
These combined signals can initiate a series of inter-spinal
reflexes that act to align the body segments.[79,85]
Therefore, converging vestibular and spinal inputs either
combine or cancel their effects so that one can attain a
position of optimum stability and orientation in space.
[86] When both the LVST and MVST were damaged in
cats, the VCR was not abolished, presumably as a result
of the activation of the reticulospinal tract.[87] With
the similar architectonic organization of descending
fibers within the spinal cord, both the vestibulospinal
and reticulospinal tracts corporate with stabilization of
posture.
Then, what is the functional difference between these
two descending tracts? Matsuyama and Drew [88,89]
examined the role of the reticulospinal and the vestib-
ulospinal tract neurons in the cat during l­ocomotion on
an inclined surface. Specifically, the vestibulospinal tract
controls primarily the overall level of postural muscle
tone, while the reticulospinal tract has an additional role
in determining the relative level of different muscles, par-
ticularly when the pattern is asymmetric.
3.2.2. Control of postural muscle tone
3.2.2.1. Functional organization of the brainstem in
the control of postural muscle tone. It is generally
agreed that the reticulospinal system contributes to
regulation of the level of muscle tone. There may exist
functional organization in the PMRF in relation to the
control of postural muscle tone (Figure 4).[48] This
was examined in decerebrate cat preparation which
maintained reflex standing posture due to decerebrate
rigidity (Figure 4(A-a)). Microsimulation applied to
the particular areas of the PMRF resulted in general
suppression of muscle tone (Figure 4(A-b)), general
augmentation of muscle tone (Figure 4(A-c)) and
tegmental reflexes or asymmetrical postural figures
(Figure 4(A-d)). The tegmental reflex is characterized
by extension of the unilateral limb and flexion of the
contralateral limb. It was observed that the ventromedial
part of the PMRF and the dorsal part of the rostral pons
including the locus coeruleus (LC) and raphe dorsalis
(RD) contributed to the muscle tone augmentation (blue
areas in Figure 4(B)). However, dorsomedial part of the
PMRF and dorsolateral part of the rostral pons including
the PPN were involved in muscle tone suppression
(red areas in Figure 4(B)). Neuroanatomical studies
revealed that RSNs in the dorsomedial and ventromedial
PMRF descend through ventral and lateral funiculi,
indicating that the ventral and lateral reticulospinal
tract are responsible for muscle tone suppression and
augmentation, respectively. Tegmental reflex was evoked
from the area between the inhibitory and excitatory
areas and the lateral part of the PMRF where few RSNs
arise in the cat (green areas in Figure 4(B)).
3.2.2.2. Role of the mesopontine tegmentum in the
control of postural muscle tone and locomotion. The
mesopontine tegmentum including the PPN has been
recognized as one of the critical areas involved in
posture–gait control.[48,90,91] The PPN is located in the
ventrolateral part of the caudal mesencephalic reticular
formation, composed of a heterogeneous population of
neurons, containing GABA and glutamate in addition
to acetylcholine. Different neuronal types within the
PPN area have different functions with their own
inter-connections to multiple parts of the brain. There
are connections to the cerebral cortex, basal ganglia
nuclei, limbic areas, thalamus, brainstem, spinal cord,
and cerebellum. This key location including multiple
segregate functions renders determining the precise
function of these regions quite complicated.
The PPN can be regarded as a part of the midbrain loco-
motor region (MLR), a functionally defined area involved
in controlling locomotion. The MLR appears to be present
in all classes of vertebrates.[92,93] It likely corresponds to
 ADVANCED ROBOTICS  9

Figure 4. Reticulospinal control of posture in decerebrate cat preparation.

Notes: (A) Postural changes in decerebrate cats. Head is fixed by stereotaxic apparatus, and body is suspended by rubber belt. The cat maintains reflex standing
posture due to decerebrate rigidity which is manifested by tonic activation of antigravity muscles (a). Stimulation of the pontomedullary reticular formation (50 Hz,
20–50 μA, 5–10 s) induces bilateral suppression (b) and augmentation (c) of postural tone, which are characterized by the changes in hip position. Reticular stimuli
also evoke tegmental reflex or asymmetrical posture which is characterized by extension of fore and hindlimbs of one side and flexion of combined with flexion
of limbs of the other side (d). (B) Functional topography of the pontomedullary reticular formation with respect to the control of hindlimb muscle tone. Results
obtained from five animals are superimposed on representative coronal planes of the rostral pons, caudal pons, and medulla. Sites from which either suppression
(red), augmentation (blue), or tegmental reflexes (green) was elicited in more than three out of five animals are marked. Sites from which the stimulation-induced
postural changes in more than four animals are indicated by darker colored squares; conversely, light colored squares indicate that the postural changes were
induced in three animals. Please see text for further explanation. (C) Organization of muscle tone inhibitory system. Cholinergic neurons in the pedunculopontine
tegmental nucleus (PPN) sequentially activate pontine reticular neurons and medullary reticulospinal neurons. (D) Organization of muscle tone excitatory system
and locomotor pathway. In addition to excitatory reticulospinal tract from the medioventral medulla, monoaminergic pathways arising from noradrenergic (NA)
and serotonergic (5-HT) neurons contribute to muscle tone augmentation. Locomotor pathway arises from glutamatergic neurons in the MLR, which corresponds
to the cuneiform nucleus (CNF) and a vicinity in the PPN, and activate excitatory reticulospinal tract. Signals from the MLR also excite monoaminergic pathways so
that excitability of spinal locomotor network is elevated. See text for further explanation. Abbreviations, LC; locus coeruleus, DR; dorsal raphe, IC; inferior colliculus,
SCP; superior cerebellar peduncle, LL; lateral lemniscus, NRPo; nucleus reticularis pontis oralis, CS; centralis superior, MLF; medial longitudinal fasciculus, NRPc;
nucleus reticularis pontis caudalis, 5ST; trigeminal spinal tract, RM; raphe magnus, TB; trapezoid body, SO; superior olive, VM; medial vestibular nucleus, NRGc;
nucleus reticularis gigantocellularis, NRMc; nucleus reticularis magnocellularis, RPa; raphe pallidus, P; pyramidal tract, ACh; acetylcholine, Glu; glutamate, NA;
noradrenaline, 5-HT; 5-hydroxy-triptamine (serotonin).

the cuneiform nucleus (CNF) and a vicinity of the PPN,
although the precise location of the locomotor regulation
still remains a matter of debate.[48,92,94,95] The PPN
is active in suppressing muscle tone via its cholinergic
projections to the pontine reticular formation (PRF)
(Figure 4(C)), while the CNF mostly elicits locomotion.
Microstimulation of the transition zone between the
two areas (ventral CNF, dorsal PPN) induced a mixture
of locomotor rhythm with associated muscle tone sup-
pression.[11,48] Moreover, injecting atropine sulfate into
the PRF blocked the PPN-induced atonia but facilitated
MLR-induced locomotion, indicating that cholinergic
PPN neurons not only control the level of muscle tone
but also modulate the locomotor pattern, and do this by
effects at the pontine level.[11,48] A recent study using
optogenetically dissection of locomotor function of the
three neurochemically distinct cell types (cholinergic,
glutamatergic, and GABAergic) within the MLR showed
that the glutamatergic subpopulation of neurons encodes
locomotor state and speed, and is necessary and sufficient
for locomotion while cholinergic neurons did not.[95]
In the ‘locomotor pathway,’ signals from the MLR also
activate medullary RSNs, in turn commanding the spinal
locomotor network to generate the oscillatory pattern of
locomotion (Figure 5).[47,96,97] Signals from the MLR
may also activate monoaminergic descending pathways
10  K. TAKAKUSAKI ET AL.
Figure 5. Spinal control of postural muscle tone.
Notes: Supraspinal command signals acting on α-motoneuron, γ-motoneuron, and Ib inhibitory interneuron play an important role in the spinal mechanisms of
regulating muscle tone. Excitability of α-motoneuron is regulated by counterbalance between length feedback from muscle spindle afferents and force feedback
from tendon organs, via Ib inhibitory interneurons. Note that the degree of length feedback is regulated by γ-motoneurons that regulate the excitability of muscle
spindles. See text for further explanation.
including the coerulospinal and raphespinal tracts, acting
as a muscle tone excitatory system (Figure 4(D)).[98,99]
Muscle tone inhibitory system arising from choliner-
gic PPN neurons is mediated by pontomedullary RSNs
(Figure 4(C)), which in turn inhibits α- and γ-motoneu-
rons that innervate extensor and flexor muscles, in parallel
with interneurons mediating reciprocal (Ia) inhibition,
non-reciprocal inhibition (Ib inhibition), recurrent inhibi-
tion, and flexion reflexes. Possibly these inhibitory effects
can be mediated by a group of inhibitory interneurons
in the Rexed lamina VII.[100] Presynaptic inhibition of
primary sensory afferents was also induced by this system.
[101,102] Accordingly, an activation of this system may
inhibit whole neuronal constituents of spinal reflex loops
including the CPG, resulting in the suppression of rhythm
generation and locomotor pattern in addition to the level
of postural muscle tone. On the other hand, selective acti-
vation of medullary RSNs by optogenetic stimulation in
rats suppressed locomotor activity without reduction of
muscle tone (halting).[103] It is therefore possible that the
inhibitory reticulospinal system enables to control muscle
tone and locomotor rhythm independently.
3.3. Spinal mechanisms of controlling posture and
movements
Spinal circuitry involved in the stretch reflex, reciprocal
Ia inhibition, non-reciprocal inhibition (Ib inhibition or
autogenic inhibition), and flexion reflexes are involved
in the control of posture. Particularly, stretch reflex and
non-reciprocal inhibition play major role in static control
of posture. On the other hand, interneuronal networks
involved in reciprocal inhibition and flexion reflexes
including crossed-extension reflex and are critical to pro-
duce postural figures with extension–flexion movements
of left–right leg alternation during walking. Integration
of all spinal reflex networks therefore can be essential to
full execution of muscle tone regulation during move-
ment. While spinal reflex networks generate rhythm and
pattern of locomotor movements through the activation
of the CPG, they play crucial role in supporting body
during stance phase of locomotion as well. Because spi-
nal preparations in quadruped animals do not express
postural reflex described above, neural networks within
the spinal cord alone does not enable to control postural
equilibrium.[96,97] Integration of descending supraspi-
nal signals and peripheral sensory afferents at the level
of spinal cord is further necessary for full execution of
postural control.
3.3.1. Spinal regulation of muscle tone
Basically, the level of muscle tone depends on the excitabil-
ity of α-motoneurons. Figure 5 illustrates our understand-
ing of the spinal mechanisms of muscle tone control during
static state. The excitability of α-motoneurons is determined
by signals in the descending motor commands and those of
 ADVANCED ROBOTICS  11

Figure 6. Central and peripheral inputs to spinal locomotor network.

Notes: Spinal interneurons largely are responsible for generation of locomotor rhythm and pattern. Signals from ‘rhythm generating’ interneurons are sent
to ‘pattern formation’ interneurons so that the template of temporal and spatial patterns of muscle contractions operating on different limb or leg joints can
be produced. The template signals are forwarded to motoneurons innervating extensor (E) and flexor (F) muscles. Activity of spinal interneurons as well as
motoneurons is modified by both peripheral sensory afferents and supraspinal motor centers (cerebral cortex and brainstem) via corticospinal tract, locomotor
pathway, and muscle tone control systems (raphespinal, coerulospinal, and reticulospinal tracts). Accordingly, postural muscle tone and locomotor rhythm can be
simultaneously regulated by supraspinal signals. See text for further explanation.

length and force feedback signals from peripheral sensory
organs. The load that is produced by muscle contractions
excites muscle spindles and tendon organs. Particularly, the
stretch reflex in which impulses generated by the excitation
of muscle spindles, via group Ia afferents, monosynapti-
cally excite homonymous and agonistic motoneurons, is
the most effective to motoneuronal excitability. Generally,
supraspinal command signals equally act on α- and γ-mo-
toneurons (α–γ linkage). Therefore, the degree of the length
feedback, which is expressed by the discharge rate of Ia
afferents from muscle spindles, depends on both the load
operating on the muscles and excitability of γ-motoneu-
rons. The α–γ linkage is revealed in the actions evoked from
the corticospinal,[104,105] vestibulospinal [106,107], and
reticulospinal [56] tracts. Inhibitory interneurons mediat-
ing autogenic or non-reciprocal inhibition (Ib inhibitory
interneurons) convert force feedback to inhibit the excit-
ability of α-motoneurons. Inhibitory Ib interneurons are
also excited by supraspinal signals arising from the corti-
cospinal, rubrospinal, and reticulospinal [108,109] tracts
also act on inhibitory Ib interneurons. Accordingly, the
excitability of motoneurons is regulated by counteraction
between length feedback (positive feedback) and force feed-
back (negative feedback). Supraspinal commands modulate
these mechanisms.
3.3.2. Spinal control of muscle tone during
locomotion
Once animals start locomotion, muscle tone must be reg-
ulated depending on locomotor cycles. Figure 6 shows the
current understanding of the spinal locomotor networks.
[8,47,96,100,110] A particular group of spinal interneu-
ronal networks that generates rhythmic activity in the
absence of rhythmic inputs is termed CPG.[43,96] The
rhythmic interneuronal activity is sent to the second-­
order interneurons in the intermediate region (lamina IV–
VII of Rexed), which shape ‘locomotor patterns’ of each
limb’s movements.[46,111] The signals are then transmit-
ted to the target motoneurons innervating ipsilateral limb
muscles through their excitatory and inhibitory actions.
[46,96] Interneurons mediating reciprocal inhibition (Ia
interneurons), non-reciprocal inhibition (Ib interneu-
rons), and recurrent inhibition (Renshaw cells) are likely
included in this group.[96] On the other hand, lamina
VIII interneurons projecting to the contralateral side con-
tribute to the left–right alternations of limb movements.
[108,112] The rhythm and pattern of locomotor move-
ments are transmitted back to the supraspinal structures
via the spinothalamic, spinoreticular, and spinocerebellar
tracts so that the supraspinal structures monitor all events
in the spinal cord.[46]
12  K. TAKAKUSAKI ET AL.

Activity of the spinal locomotor networks is modu- 4.1. Cortical contribution of postural control
lated by sensory afferents in a phase-dependent manner.
4.1.1. Cortical control of vertical posture
[96,111,113,114] For example, proprioceptors in muscles
How does the brain access to an internal estimate of body
at the hip joint are primarily responsible for regulating the
motion and postural verticality? Postural vertical is sup-
stance phase. Preventing hip extension suppresses step-
ported by a sense of verticality which is synthesized by
ping, whereas rhythmically moving the hip can entrain
visual, somatosensory, and vestibular information.[120–
the locomotor rhythm.[113] Afferents from propriocep-
124] Among various sensations, the vestibular sensation
tors in extensor muscles regulate transition from stance
is superior to other sensations in terms of absoluteness of
to swing phase. It should be critically mentioned that
sensation because it always refers the gravity,[125] and the
signals in Ib afferents from tendon organ in ankle exten-
vestibular system provides the brain with sensory signals
sor muscles inhibit homonymous motoneurons in rest,
about three-dimensional head rotations and translations.
while they excite extensor motoneurons during stance
Vestibulothalamic projections are bilateral and mainly
phase.[96,113] The functional consequence of this ‘reflex
involve the posterior thalamus.[126–128] While there
reversal’ is that the swing phase is not initiated until the
was no primary vestibular cortex that obtains projections
extensor muscles are unloaded and the forces exerted
exclusively from vestibular afferents, there are multiple
by these muscles are low. The continuous regulation of
presentations of vestibular information in the cerebral
extensor muscle tone by proprioceptive feedback presum-
cortex (Figure 7(A)).[129] These areas are distributed
ably allows automatic adjustment of force and length in
to the frontal eye field, premotor area, somatosensory
extensor muscles in response to the changes in loading
cortex, ventral intraparietal cortex, medial superior tem-
of the leg. Skin afferents also exert a powerful influence
poral area, and parieto-insular vestibular cortex (PIVC).
on the CPG.[46,96,113] Skin receptors are important to
Among them, the PIVC has dense connections with other
detect obstacles and adjust stepping to avoid them such
vestibular-relating cortical areas and receive information
as the ‘stumble-corrective reaction,’[115] which must be
from other sensory modalities.[125–132] It is now consid-
produced to a large extent by spinal circuits. Importantly,
ered that the posterior thalamus and the PIVC are areas
the corrective flexion movements are produced only if the
of interest for the internal model of postural verticality.
paw is stimulated during the swing phase. An identical
[133–137] Because the PIVC has descending connec-
stimulus applied during stance phase elicits the opposite
tions to the contralateral vestibular nuclei,[128,138–140]
response, an excitation of extensor muscles that reinforces
it can be postulated that the vestibular cortical system has
the ongoing extensor activity. This is another example of
a direct influence on the vestibulospinal system so that
the reflex reversal. The reflex reversal phenomenon is
one can maintain upright standing posture based on the
critically involved in postural control during locomotion.
information of the internal model of postural verticality
However, its mechanisms have not been elucidated.
(Figure 7(C)).
Postural verticality is often disturbed in pathological
4. Higher order regulation of posture by the conditions such as ‘pusher syndrome’ after stroke and ‘Pisa
cerebral cortex, cerebellum, and basal ganglia syndrome’ in advanced Parkinson’s disease. Stroke patients
with pusher syndrome actively push away from the ipsile-
Knowledge of the orientation and motion of the body in
sional side and have a tendency to fall toward their paretic,
space is important for the control of body, limb, and neck
contralesional side (the left side for right-hemisphere
posture as well as motion perception and spatial localiza-
patients). They had lesions including the parietal insular
tion of objects in extra-personal space.[116–118] Such a
cortex or posterior thalamus.[133,136,137,141] This phe-
knowledge is provided by integration of vestibular, soma-
nomenon is more prominent when patients are upright
tosensory, and visual sensory signals which occurs at both
compared to when lying down. Now the pusher phenom-
the cerebral cortex and cerebellum (Figure 7(A)).[119]
enon can be arising from a conflict or mismatch between
The brainstem receives direct inputs from the cerebral
visual and postural vertical.[133,137,142] Possible mech-
cortex and cerebellum in addition to the basal ganglia
anisms of Pisa syndrome will be discussed in section 4.3.
(Figure 1). Therefore, postural control largely depends
on the cognitive information derived from the higher
centers together with postural control systems within 4.1.2. Cortical and subcortical mechanisms of APA
the brainstem and spinal cord. Because postural control Precise visuomotor coordination, which is occurred at
is seriously impaired by damages in the cerebral cortex, the cerebral cortex, plays critical roles in the execution of
cerebellum, and basal ganglia, we review how these higher precise arm–hand movements such as reaching and grasp-
motor centers contribute to the postural control by acting ing.[2,3] Similarly, when a walking subject encounters
on the brainstem structures. obstacles, each leg must be placed with a high degree of
 ADVANCED ROBOTICS  13

Figure 7. Cognitive process of postural control.

Notes: (A) Construction of bodily information. Sensory signals flowing into the central nervous system converge to the brainstem, cerebellum, thalamus, and
cerebral cortex. At the level of cerebral cortex, signals from the visual cortex, vestibular cortex and primary sensory cortex (S1) is integrated and internal model
of self-body, such as body schema and verticality can be constructed at the temporoparietal cortex including the vestibular cortex and posteroparietal cortex.
The cerebellum may also contribute to this process. (B) Motor programming. The bodily information is then transmitted to the supplementary motor area (SMA)
and premotor area (PM) where the information can be utilized as materials to produce motor programs. The motor cortical areas closely cooperate with the
basal ganglia and cerebellum so that appropriate motor programs are constructed. Intentional signal from the prefrontal cortex (PFC) may trigger to run motor
programs. (C) Postural control by corticofugal projections to the brainstem and spinal cord. The bodily information generated at the vestibular cortex may be
utilized for sustention of vertical posture via cortico-vestibular and vestibulospinal tract. The motor programs in the SMA/PM may include those for purposeful
movements and associating postural control. The postural control program may be utilized to generate anticipatory postural adjustment via cortico-reticular and
reticulospinal tract. Then motor programs are sent to primary motor cortex (M1) so that goal-directed purposeful movements can be achieved.
14  K. TAKAKUSAKI ET AL.
accuracy through the visuo–parieto–frontal cortical pro-
jection, as in the subject has to modify the leg trajectory
in each step in order to achieve appropriate foot place-
ment.[143] Such a visuomotor coordination is particularly
necessary in quadrupeds because an obstacle is no longer
within the visual field by the time the hindlimbs are step-
ping over it. Drew and his colleagues demonstrated, when
the posterior parietal cortex was bilaterally removed, the
cat’s hindlimbs did not step over the obstacles if their fore-
limbs cleared them.[144] They suggest that the posterior
parietal cortex must be engaged to register and store the
temporospatial relationship between the obstacle and
one’s bodily information, such as body schema, in short-
term memory that is utilized to produce motor programs
in the motor cortices so that the cat can precisely modify
the limb trajectory based on visual information.[144–146]
To successfully achieve such an accurate control of limb
movements during walking, appropriate postural adjust-
ment that is optimized to the purposeful action has to
be preceded so that bodily equilibrium can maintained.
Therefore, the visuo–parieto–frontal cortical projection is
critically involved in the fulfillment of ongoing purposeful
control via anticipatory adjustments of posture.[4] It fol-
lows that both the intentional limb movements and APA
are programmed at motor cortical areas.
Then, what part of the motor cortex contributes to
the programming of the APA? One of the most candi-
date areas is the supplementary motor area (SMA) and
premotor area (PM) (Figure 7(B)). Nakajima et al. [147]
demonstrated that inactivation of the leg area of the
primary motor cortex (M1) by injections of muscimol
(GABAA agonist) resulted in paresis of the contralateral
leg engaged in unrestrained bipedal walking in monkey.
On the other hand, muscimol injections into the trunk/
leg regions of the bilateral SMA largely disturbed pos-
tural control without inducing paralysis.[148] When an
injection was administered into the dorsal PM, sponta-
neous walking was maintained in the monkey; however,
the monkey could not start locomotion using sensory
cue. These findings indicate the presence of functional
organization in the motor cortical areas in the control
of posture and locomotion in bipedal walking animals,
and the SMA and PM may contribute to postural control
during walking and initiation of gait, respectively.
It has been shown, while neurons in the M1 project
mainly to the spinal cord, neurons in the SMA/PM have
dense projections to the PMRF in addition to the spinal
cord.[149,150] The reticulospinal tract innervates whole
spinal segments (Figure 2(B)) [112] so that it controls
postural muscle tone and symmetric postural figures.[48]
Therefore, the corticoreticular and the reticulospinal tract
may achieve postural preparation or APA (Figure 7(C)).
It is particularly important to determine whether these
pathways contribute to the APA by using animal experi-
mentation and clinical examination. On the other hand,
the PM/SMA may forward programs of precise leg–foot
movement to the M1,[151] which, in turn, sends motor
command via the corticospinal tract. Consequently, cog-
nitive information processing in the temporoparietal
cortex is essential for accurate gait control particularly
when the subject encounters an unfamiliar environment.
Therefore, the deficiency in the information processing
from the temporoparietal cortex to the frontal cortex may
cause errors in APA and gait difficulties such as the ‘freez-
ing of gait.’ It follows that deficits in cognitive function in
elder persons and in patients with Alzheimer’s disease are
at higher risk of falling particularly when more cognitive
tasks are required.[152,153]
4.2. Cerebellar regulation of postural muscle tone
Patients with damages in the medial cerebellum suffer
from impaired postural control, often called as truncal
ataxia, which is characterized by postural sway, hypo-
tonia, and discoordination of trunk–limb movements
(dis-synergia). The cerebellum has reciprocal connections
with the brainstem, particularly the vestibular nuclei and
reticular formation, cerebral cortex, and basal ganglia.
Through these connections, the cerebellum contributes
to the control of postural reflexes, postural muscle tone,
and cognitive process of postural control.
4.2.1. Cerebellar modulation of the automatic
process of postural control
Postural control by the cerebellum highly depends on
sensory afferents (Figure 7(A)). The labyrinthine signal
ascends the VIII-th cranial nerve to the floccules and
vermis of the cerebellum in addition to the vestibular
nuclei. Fastigial nuclei (FN), cerebellar nuclei located in
the medial part of the cerebellum, receive a copy of the
output of spinal cord in addition to peripheral sensory
information via spinocerebellar tracts and the vermis.
[154] The FN also receive visual [155] and vestibular
information.[156] These complex, multisensory features
may provide ‘an error-correction mechanism,’ which per-
mits FN neurons to affect motor functions such as coor-
dinating postural responses during locomotion and other
movements which entail changes in limb position. The FN
may therefore send highly integrated bodily information
during ongoing movements to the posture–gait-related
areas in the brainstem and motor cortical areas via the
thalamocortical projections.[157]
Output from the FN to the brainstem contributes to the
control of postural muscle tone (Figure 7(C)). Electrical
stimulation applied to the mid-part of the cerebellar
white matter in decerebrate cats either increased [158] or

decrease the level of muscle tone.[159] The muscle tone
augmentation is possibly caused by the activation of the
passing fibers arising from the bilateral FN. The cerebel-
lar stimulation possibly activated the excitatory reticu-
lospinal tract and vestibulospinal tract so that extensor
muscle tone was bilaterally increased. On the other hand,
the decrease in the level of muscle tone is considered to
be due to withdrawal of excitatory influence upon moto-
neurons.[159] However, postural muscle tone is usually
reduced in patients with mid-cerebellar lesions, cerebel-
lum generally contributes to maintain the level of muscle
tone. It can be considered that the FN possesses potential
capability to recruit and regulate postural- and locomo-
tor-related subprograms which are distributed within the
brainstem and spinal cord by the in-parallel activation of
fastigio-spinal, fastigio-reticular, and fastigio-vestibular
pathways.[160–163] Therefore, the degree of α–γ linkage
which is provided by the vestibulospinal and excitatory
reticulospinal tracts may be reduced in patients with
­cerebellar diseases, resulting in hypotonia. The hypotonia
state may decrease the accuracy of the sensory feedback
and increase postural sway.
4.2.2. Cerebellar regulation of cognitive process of
postural control
Reciprocal connections between the cerebellum and cere-
bral cortex (Figure 7(B)) may be critically involved in the
cognitive processes of postural control. It has been recently
recognized that cerebellar output reaches vast areas of the
neocortex including regions of the prefrontal and pos-
terior parietal cortices in addition to motor areas.[164]
The FN in the cerebellum, as well as the vestibular cortex
(PIVC), is critically involved in encoding internal postural
model in space and self-motion.[119] Some studies have
suggested the presence of FN projections to the parietal
cortex,[165,166] motor cortex, and multimodal visual
areas.[167] Reciprocal connection between the parietal
cortex and the cerebellum may be involved in perception
of body motion in space. Such a bodily information can
be utilized to maintain upright posture during standing
and to achieve APA. The latter may involve reciprocal
connections between the motor cortical area (SMA/PM)
and cerebellum (motor loop) so that motor programs are
constructed (Figure 7(C)).[6,32] Accordingly, cerebellar
disease patients may have problems in cognitive process
of postural control. However, the perception of verticality
in patients with cerebellar ataxia may only deteriorate in a
more advanced stage of the disease.[168] In addition, only
few abnormalities of APA were found in the cerebellar
disease patients compared to controls, while the patients
appeared to be less able to use predictive information.
[169] Because the cerebellum is reciprocally connected
with the basal ganglia,[164,170] it is possible that basal
ADVANCED ROBOTICS  15
ganglia in addition to the cerebral cortex may complement
the cerebellar role of cognitive process of postural control.
4.3. Basal ganglia control of posture with reference
to pathophysiology of Parkinson’s disease
Because posture–gait control is seriously impaired in PD,
which is the most famous basal ganglia disorder due to
deficit in midbrain dopamine (DA) neurons, the basal
ganglia has long been functionally regarded to be predom-
inantly involved in motor control but are increasingly rec-
ognized to play an additional role in sensory processing,
cognition, and behavior.[171–173] Here, we particularly
focus on the mechanisms of postural impairment in PD so
that understanding the contribution of the basal ganglia to
postural control is facilitated. Based on our understand-
ing, postural disturbances in PD can be induced by follow-
ing mechanisms: (1) impairment of cognitive functions
due to failure of integrative sensory processing that may
allow to construct internal postural model, (2) reduced
capability in motor programming due to reduced activity
in the motor cortical areas, and (3) reduced excitability
of muscle tone inhibitory system,[11,63] which induces
hypertonus (muscular rigidity) or co-contractions of
extensor and flexor muscles of limb and trunk, resulting
in flexion posture.
4.3.1. Failure in dopaminergic and cholinergic
systems in PD
Recent clinical studies suggest that the postural impair-
ments in PD is based on dysfunction of both the dopa-
minergic and non-dopaminergic, particularly cholinergic,
system. Basically, damages of these chemo-specific sys-
tems may critically contribute to posture–gait failure in
this disease. For example, a damage of DA neurons in
the substantia nigra pars compacta (SNc) which project
to the basal ganglia nuclei may be considered to increase
GABAergic inhibitory output from the basal ganglia.[174–
176] This may strongly inhibit the thalamocortical systems
and brainstem structures (Figure 1). In addition, cholin-
ergic neurons in the PPN (brainstem) and basal forebrain
(BF) are seriously damaged in PD.[177–180] Cholinergic
PPN neurons project to the non-specific thalamocortical
system,[181–183] basal ganglia nuclei including SNc-DA
neurons [184–186] and PMRF. On the other hand, cholin-
ergic BF projections to the cerebral cortex are necessary
for attentional performance and cognitive processing.
[187] Therefore, disturbances in attention, sensorimotor
integration and cognitive processing in PD can be largely
attributed to the damage of the cholinergic systems that
have such unique anatomical and physiological position.
Accordingly, both of the excessive inhibition from the
basal ganglia and the damage of cholinergic systems may
16  K. TAKAKUSAKI ET AL.
impair cortical and subcortical (particularly the brain-
stem) functions.
4.3.2. Failure in sensory processing and cognition in
PD
Cortical activity was substantially reduced in patients
in PD compared control subject during walking.[188]
Reduced cortical activity may cause failure of integrative
sensory processing, which in turn, disturb construction
internal postural model and motor programming. It has
been shown that a loss of cholinergic neurons in the BF
and PPN associates with fallers in PD.[177,189] Müller
et al. [190] suggested that reduced activities in the cholin-
ergic PPN neurons may disturb multi-sensory integration
at the level of the thalamus. This may also explain why
patients in PD with more severe posture–gait instability
have a high risk of developing dementia.[191] Impairment
of the central integration of sensory information, particu-
larly proprioception [192] or vestibular graviception,[193]
may result in deficits of internal model of postural verti-
cality, which is possibly constructed at the temporopari-
etal cortical area such as the vestibular cortex. Asymmetry
of the activity in the left and right vestibular cortex may
induce leaning of upright standing posture, which is char-
acterized as Pisa syndrome. Pisa syndrome is a dystonic
lateroflexion of the trunk with a postural disturbance
resembling the leaning tower of Pisa, and is more often
observed in patients with advanced PD.[194] The marked
lateroflexion becomes worse during walking but is almost
completely alleviated by passive mobilization or supine
positioning.[195] Because PD without Pisa syndrome
also had deficiencies in postural verticality compared to
healthy controls,[192,196–198] mismatch between pro-
prioception and vestibular gravitation may alter subjec-
tive postural vertical in PD, resulting in Pisa syndrome.
Alternatively, asymmetry of basal ganglia output due to
cholinergic–dopaminergic imbalance in the striatum
[199,200] and disturbance of pallidal output [201,202]
may elicit imbalance of the thalamocortical processing
of vestibular information.
4.3.3. Failure in motor programming
The motor cortical areas including the M1, SMA and
PM have connections with the basal ganglia and cerebel-
lum, constituting motor loop that contributes to execu-
tion and motor programming of voluntary movements
(Figure 7(B)).[6,32] Because of increasing inhibitory
output from the basal ganglia to the thalamocortical
projections in addition to reduced cognitive information
processing, the capability of producing motor programs
in response to changes in circumstance can be deterio-
rated. In fact, the SMA contributes to APA for step initi-
ation via corticofugal projections to the PPN and PMRF,
and this process is seriously impaired in PD patients.
[203] Also, the dorsal part of the PM is involved in senso-
ry-guided gait control as suggested in bipedally walking
monkey.[147] Because the activity of dorsal part of the
PM was increased during visually-guided paradoxical
gait in PD patients, posture–gait programs in SMA/PM
became reusable by the activation of visuo-motor path-
way.[204] Accordingly, failure in motor programming
in PD can be due to the decrease in excitability of the
motor cortical areas in addition to the temporoparietal
cortices where cognitive self-bodily information can be
produced by integrating multi-sensory signals. Recently,
role of the cerebellum in the pathophysiology of PD is
highly recognized.[205,206] Because the cerebellum has
reciprocal connections with the basal ganglia in addition
to the cerebral cortex and brainstem, there is a need to
elucidate whether the cerebellum participates in com-
pensatory mechanisms associated with the disease or
contributes to the pathophysiology of PD.
4.3.4. Reduced activity in the posture–gait area in the
midbrain
Reduced excitability in the mesopontine t­egmentum
including the PPN/MLR can be also involved in
­posture–gait failure in this disease.[11,47,48] In decer-
ebrate cats, the basal ganglia control locomotion and
posture using different GABAergic output pathways of
the substantia nigra reticulata (SNr); the lateral part of
the SNr blocks the PPN-induced muscle tone suppres-
sion, whereas the medial part of the SNr suppresses
the MLR-induced locomotion.[11] Recent rat studies
confirm that inhibitory input from the SNc to the glu-
tamatergic neurons in the MLR regulates locomotion.
[95,205] In PD, GABAergic outputs of the basal gan-
glia are abnormally increased,[174–176] so excessive
SNr-inhibition of the MLR may cause gait disturbance
and muscle rigidity.[11] Muscle tone rigidity in PD is
called as ‘lead-pipe like rigidity’ which is character-
ized by co-contraction of extensor and flexor muscles.
Such a co-contraction is observed in neck, back, and leg
muscles, resulting in flexion posture including camp-
tocormia.[195]
As one of clinical procedures for alleviating gait-­
posture deficiency in PD, deep brain stimulation (DBS)
targeting the PPN with the aim of stimulating remaining
cholinergic neurons.[207–210] The first studies using DBS
in advanced PD patients concluded that low-­frequency
­stimulation of the PPN could be effective to control
freezing of gait and falls.[211,212] However, further
­
­clinical studies concluded that freezing of gait were mildly
improved by PPN–DBS but the overall results were rather
disappointing.[213–215] These results emphasize the need
to determine the optimal surgical target.[215]

Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was partially supported by grants from JSPS
KAKENHI [grant number 26120004] and [grant number
25290001] for K.T., [grant number 26120006] and [grant num-
ber 15K06131] for R.C. KT is also supported by foundations
from the QOLER Medical Group and Sasson Hospital.
Notes on contributors
Kaoru Takakusaki received MD degree in
1984 and PhD degree in Asahikawa Medical
College in 1988. Currently, he is working as a
director and a professor of Research Center
for Brain Function and Medical Engineering
in Asahikawa Medical University. His current
research interest is neuroscience in general.
Mirai Takahashi received MD degree in
Asahikawa Medical College in 2010. He had
been working at Tokyo Saiseikai Central hos-
pital as an acute care physician for 6 years.
Currently, he is working as a research associ-
ate of Research Center for Brain Function and
Medical Engineering in Asahikawa Medical
University. His current research interest is
neuroscience in critical care.
Kazuhiro Obara received MD degree in 1996
in Asahikawa Medical College. He has been
working as orthopedic surgeon in Asahikawa
Medical University and a physical sports doc-
tor of All Nippon Women’s Volleyball Team.
Currently, he is working as Assistant Professor
of Research Center for Brain Function and
Medical Engineering in Asahikawa Medical
University. His research specialty is sports medicine.
Ryosuke Chiba received the BS, MS, and PhD
degrees in precision mechanical engineering
from the University of Tokyo, Tokyo, Japan, in
1999, 2001, and 2004, respectively. In 2002, he
visited the University of Edinburgh and
researched a coevolutional design process.
From 2004 to 2008, he was a project assistant
researcher with the Department of Precision
Engineering, University of Tokyo. From 2008 to 2014, he was
an assistant professor at Tokyo Metropolitan University.
Currently, he is an associate professor with Asahikawa Medical
University. His research interests are coevolutional design pro-
cesses and modeling of human posture control.
References
[1] Branke O. Multisensory brain mechanisms of bodily
self-consciousness. Nat Rev Neurosci. 2012;13:556–571.
ADVANCED ROBOTICS  17
[2] Murata A, Wen W, Asama H. The body and objects
represented in the ventral stream of the parieto-
premotor network. Neurosci Res. 2016;104:4–15.
[3] Kravitz DJ, Saleem KS, Baker CI, et al. A new neural
framework for visuospatial processing. Nat Rev
Neurosci. 2011;12:217–230.
[4] Massion J. Movement, posture and equilibrium:
interaction and coordination. Prog Neurobiol.
1992;38:35–56.
[5] Brooks VB., III. Posture and locomotion. In: The neural
basis of motor control. New York, NY: Oxford University
Press; 1986. p. 140–150.
[6] Middleton FA, Strick PL. Basal ganglia and cerebellar
loops: motor and cognitive circuits. Brain Res Rev.
2000;31:236–250.
[7] Takakusaki K. Forebrain control of locomotor behaviors.
Brain Res Rev. 2008;57:192–198.
[8] Grillner S. Control of locomotion in bipeds, tetrapods,
and fish. In: Brooks VB, editor. The nervous system II.
Bethesda, ML: Am Physiol Soc Press; 1981. p. 1179–
1236.
[9] Sinnamon HM. Preoptic and hypothalamic neurons
and the initiation of locomotion in the anesthetized rat.
Prog Neurobiol. 1993;41:323–344.
[10] Takakusaki K, Saitoh K, Harada H, et al. Role of basal
ganglia – brainstem pathways in the control of motor
behaviors. Neurosci Res. 2004;50:137–151.
[11] Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J,
et al. Basal ganglia efferents to the brainstem centers
controlling postural muscle tone and locomotion: a new
concept for understanding motor disorders in basal
ganglia dysfunction. Neuroscience. 2003;119:293–308.
[12] DeLong MR. Primate models of movement disorders
of basal ganglia origin. Trends Neurosci. 1990;13:281–
285.
[13] Bard P, Macht MB. The behavior of chronically
decerebrate cat. In: Wolstenholme GEW, O’Connor
CM, editors. Neurological basis of behavior. London:
Churchill; 1958. p. 55–71.
[14] Deliagina TG, Beloozerova IN, Zelenin PV, et al. Spinal
and supraspinal postural networks. Brain Res Rev.
2008;57:212–221.
[15] Lawrence DG, Kuypers HG. Pyramidal and non-
pyramidal pathways in monkeys: anatomical and
functional correlation. Science. 1965;148:973–975.
[16] Peterson BW, Fukushima K, Hirai N, et al. Responses of
vestibulospinal and reticulospinal neurons to sinusoidal
vestibular stimulation. J Neurophysiol. 1980;43:1236–
1250.
[17] Wilson VJ, Maeda M. Connection between semicircular
canals and neck motoneurons in the cat. J Neurophysiol.
1974;37:346–357.
[18] Akaike T, Westerman RA. Spinal segmental levels
innervated by different types of vestibulo-spinal tract
neurons in rabbit. J Neurophysiol. 1973;17:443–446.
[19] Wilson VJ, Yoshida M, Schor RH. Supraspinal
monosynaptic excitation and inhibition of thoracic back
motoneurons. Exp Brain Res. 1970;11:282–295.
[20] Carleton SC, Carpenter MB. Afferent and efferent
connections of the medial, inferior and lateral vestibular
nuclei in the cat and monkey. Brain Res. 1983;278:29–51.
18  K. TAKAKUSAKI ET AL.
[21] Pompeiano O. Vestibulospinal relations: vestibular
influences on gamma motoneurons and primary
afferents. Prog Brain Res. 1972;37:263–296.
[22] Kuze B, Matsuyama K, Matsui T, et al. Segment-specific
branching patterns of single vestibulospinal tract axons
arising from the lateral vestibular nucleus in the cat: a
PHA-L tracing study. J Comp Neurol. 1999;414:80–96.
[23] Abzug C, Maeda M, Peterson BW, et al. Cervical
branching of lumbar vestibulospinal axons. J Physiol.
1974;243:499–522.
[24] Shinoda Y, Ohgaki T, Futami T. The morphology
of single lateral vestibulospinal tract axons in the
lower cervical spinal cord of the cat. J Comp Neurol.
1986;249:226–241.
[25] Yates BJ, Stocker SD. Integration of somatic and visceral
inputs by the brainstem: functional considerations. Exp
Brain Res. 1998;119:269–275.
[26] Gaymard B, Pierrot-Deseilligny C. Neurology of
saccades and smooth pursuit. Curr Opin Neurol.
1999;12:13–19.
[27] Sparks DL. Translation of sensory signals into commands
for control of saccadic eye movements: role of primate
superior colliculus. Physiol Rev. 1986;66:118–171.
[28] Yeomans JS, Li L, Scott BW, et al. Tactile, acoustic
and vestibular systems sum to elicit the startle reflex.
Neurosci Biobehav Rev. 2002;26:1–11.
[29] Budinger E, Heil P, Hess A, et al. Multisensory
processing via early cortical stages: connections of
the primary auditory cortical field with other sensory
systems. Neuroscience. 2006;143:1065–1083.
[30] Steriade M, McCormick DA, Sejnowski TJ.
Thalamocortical oscillations in the sleeping and aroused
brain. Science. 1993;262:679–685.
[31] Hikosaka O. GABAergic output of the basal ganglia.
Prog Brain Res. 2007;160:209–226.
[32] Hikosaka O, Nakahara H, Rand MK, et al. Parallel
neural networks for learning sequential procedures.
Trends Neurosci. 1999;22:464–471.
[33] Hikosaka O, Takikawa Y, Kawagoe R. Role of the
basal ganglia in the control of purposive saccadic eye
movements. Physiol Rev. 2000;80:953–978.
[34] Grantyn A, Berthoz A. Reticulo-spinal neurons
participating in the control of synergic eye and head
movements during orienting in the cat. I. Behavioral
properties. Exp Brain Res. 1987;66:339–354.
[35] Grantyn A, Ong-Meang Jacques V, Berthoz A. Reticulo-
spinal neurons participating in the control of synergic
eye and head movements during orienting in the cat. II.
Morphological properties as revealed by intra-axonal
injections of horseradish peroxidase. Exp Brain Res.
1987;66:355–377.
[36] Bianchi A, Gestreau C. The brainstem respiratory
network: an overview of a half century of research.
Respir Physiol Neurobiol. 2009;168:4–12.
[37] Harada H, Takakusaki K, Kita S, et al. Effects of
injecting GABAergic agents into the medullary reticular
formation upon swallowing induced by the superior
laryngeal nerve stimulation in decerebrate cats. Neurosci
Res. 2005;51:395–404.
[38] Jean A. Brain stem control of swallowing: neuronal
network and cellular mechanisms. Physiol Rev.
2001;81:929–969.
[39] Drew T, Rossignol S. Functional organization within the
medullary reticular formation of intact unanesthetized
cat. I. Movements evoked by microstimulation.
J Neurophysiol. 1990;64:767–781.
[40] Drew T, Rossignol S. Functional organization within the
medullary reticular formation of intact unanesthetized
cat. II. Electromyographic activity evoked by
microstimulation. J Neurophysiol. 1990;64:782–795.
[41] Drew T, Dubuc R, Rossignol S. Discharge patterns of
reticulospinal and other reticular neurons in chronic,
unrestrained cats walking on a treadmill. J Neurophysiol.
1986;55:375–401.
[42] Garcia-Rill E. The basal ganglia and the locomotor
regions. Brain Res Rev. 1986;11:47–63.
[43] Grillner S. Control of locomotion in bipeds, tetrapods,
and fish. In: Brooks VB, editor. The nervous system II.
Bethesda, ML: Am Physiol Soc Press; 1981. p. 1179–
1236.
[44] Mori S. Integration of posture and locomotion in acute
decerebrate cats and in awake, freely moving cats. Prog
Neurobiol. 1987;28:161–195.
[45] 
Prentice SD, Trevor Drew T. Contributions of the
reticulospinal system to the postural adjustments occurring
during voluntary gait modifications. J Neurophysiol.
2001;85:679–698.
[46] Rossignol S. Neural control of stereotypic limb
movements. In: Rowell LB, Shepherd JT, editors.
Handbook of physiology, Sec 12. New York, NY: Oxford
University Press; 1996. p. 173–216.
[47] Takakusaki K. Neurophysiology of gait: from the spinal
cord to the frontal lobe. Mov Disord. 2013;28:1483–
1491.
[48] Takakusaki K, Chiba R, Nozu T, et al. Brainstem control
of locomotion and muscle tone with special reference to
the role of the mesopontine tegmentum and medullary
reticulospinal systems. J Neural Transm (Vienna).
2016;123:695–729. Oct 26.
[49] Brodal A. Neurological anatomy in relation to clinical
medicine. Oxford: Oxford University Press; 1981.
p. 394–447.
[50] Peterson BW, Maunz RA, Pitts NG, et al. Patterns of
projection and branching of reticulospinal neurons. Exp
Brain Res. 1975;23:333–351.
[51] Matsuyama K, Kobayashi Y, Takakusaki K, et al.
Termination mode and branching patterns of
reticuloreticular and reticulospinal fibers of the nucleus
reticularis pontis oralis in the cat: an anterograde PHA-L
tracing study. Neurosci Res. 1993;17:9–21.
[52] Matsuyama K, Ohta Y, Mori S. Ascending and descending
projections of the nucleus reticularis gigantocellularis in
the cat demonstrated by the anterograde neural tracer,
Phaseolus vulgaris leucoagglutinin (PHA-L). Brain Res.
1988;460:124–141.
[53] Sakai ST, Davidson AG, Buford JA. Reticulospinal
neurons in the pontomedullary reticular formation
of the monkey (Macaca fascicularis). Neuroscience.
2009;163:1158–1170.
[54] 
Kohyama J, Lai YY, Siegel JM. Reticulospinal systems
mediate atonia with short and long latencies. J Neurophysiol.
1998;80:1839–1851.
[55] Habaguchi T, Takakusaki K, Saitoh K, et al. Medullary
reticulospinal tract mediating the generalized motor

inhibition in cats: II. Functional organization within
the medullary reticular formation with respect to
postsynaptic inhibition of forelimb and hindlimb
motoneurons. Neuroscience. 2002;113:65–77.
[56] Takakusaki K, Kohyama J, Matsuyama K, et al. Medullary
reticulospinal tract mediating the generalized motor
inhibition in cats: parallel inhibitory mechanisms acting
on motoneurons and on interneuronal transmission in
reflex pathways. Neuroscience. 2001;103:511–527.
[57] Peterson BW. The reticulospinal system and its role
in the control of movement. In: Barnes CD, editor.
Brainstem control of spinal cord function. London:
Academic Press; 1984. p. 27–86.
[58] Peterson BW, Pitts NG, Fukushima K. Reticulospinal
connections with limb and axial motoneurons. Exp
Brain Res. 1979;36:1–20.
[59] Takakusaki K, Ohta Y, Mori S. Single medullary
reticulospinal neurons exert postsynaptic inhibitory
effects via inhibitory interneurons upon alpha-
motoneurons innervating cat hindlimb muscles. Exp
Brain Res. 1989;74:11–23.
[60] Takakusaki K, Shimoda N, Matsuyama K, et al. Discharge
properties of medullary reticulospinal neurons during
postural changes induced by intrapontine injections of
carbachol, atropine and serotonin, and their functional
linkages to hindlimb motoneurons in cats. Exp Brain
Res. 1994;99:361–374.
[61] Jordan LM, Liu J, Hedlund PB, et al. Descending
command systems for the initiation of locomotion in
mammals. Brain Res Rev. 2008;57:183–191.
[62] Takakusaki K, Habaguchi T, Saitoh K, et al. Changes in the
excitability of hindlimb motoneurons during muscular
atonia induced by stimulating the pedunculopontine
tegmental nucleus in cats. Neuroscience. 2004;124:467–
480.
[63] Takakusaki K, Obara K, Nozu T, et al. Modulatory
effects of the GABAergic basal ganglia neurons on the
PPN and the muscle tone inhibitory system in cats. Arch
Ital Biol. 2011;149:385–405.
[64] Fung SJ, Boxer PA, Morales FR, et al. Hyperpolarizing
membrane responses induced in lumbar motoneurons
by stimulation of the nucleus reticularis pontis oralis
during active sleep. Brain Res. 1982;248:267–273.
[65] Chase MH, Morales FR, Boxer P, et al. Effect of stimulation
of the nucleus reticularis gigantocellularis on the membrane
potential of cat lumbar motoneurons during sleep and
wakefulness. Brain Res. 1986;386:237–244.
[66] May PJ. The mammalian superior colliculus:
laminar structure and connections. Prog Brain Res.
2006;151:321–378.
[67] Shinoda Y, Kakei S, Muto N. Morphology of single axons
of tectospinal and reticulospinal neurons in the upper
cervical spinal cord. Prog Brain Res. 1996;112:71–84.
[68] Basbaum AL, Fields HL. Endogenous pain control
systems: brainstem spinal pathways and endorphin
circuitry. Annu Rev Neurosci. 1984;7:309–338.
[69] Shaikh AG, Meng H, Angelaki DE. Multiple reference
frames for motion in the primate cerebellum. J Neurosci.
2004;24:4491–4497.
[70] Outerbridge JS, Jones GM. Reflex vestibular control of
head movement in man. Aerosp Med. 1971;42:935–940.
ADVANCED ROBOTICS  19
[71] Sugiuchi Y, Kakei S, Izawa Y, et al. Functional synergies
among neck muscles revealed by branching patterns of
single long descending motor-tract axons. Prog Brain
Res. 2004;143:411–421.
[72] Peterson BW, Goldberg J, Bilotto G, et al. Cervicocollic
reflex: its dynamic properties and interaction with
vestibular reflexes. J Neurophysiol. 1985;54:90–109.
[73] McCrea RA, Yoshida K, Berthoz A, et al. Eye movement
related activity and morphology of second order
vestibular neurons terminating in the cat abducens
nucleus. Exp Brain Res. 1980;40:468–473.
[74] Vidal PP, Roucoux A, Berthoz A. Horizontal eye
position-related activity in neck muscles of the alert cat.
Exp Brain Res. 1982;46:448–453.
[75] Bronstein AM, Hood JD. The cervico-ocular reflex in
normal subjects and patients with absent vestibular
function. Brain Res. 1986;373:399–408.
[76] Grantyn A, Berthoz A. Burst activity of identified tecto-
reticulo-spinal neurons in the alert cat. Exp Brain Res.
1985;57:417–421.
[77] Cohen B, Tokumasu K, Goto K. Semicircular canal
nerve eye and head movements. The effect of changes in
initial eye and head position on the plane of the induced
movement. Arch Ophthalmol. 1966;76:523–531.
[78] Suzuki JI, Cohen B. Head eye body and limb movements
from semicircular canal nerves. Exp Neurol.
1964;10:393–405.
[79] Roberts TD. Biological Sciences: Reflex Balance. Nature.
1973;244:156–158.
[80] Schor RH. Responses of cat vestibular neurons to
sinusoidal roll tilt. Brain Res. 1974;79:347–351.
[81] Jones GM, Watt DG. Observations on the control of
stepping and hopping movements in man. J Physiol.
1971;219:709–727.
[82] Watt DG. Responses of cats to sudden falls: an otolith-
originating reflex assisting landing. J Neurophysiol.
1976;39:257–265.
[83] Wicke RW, Oman CM. Visual and graviceptive
influences on lower leg EMG activity in humans during
brief falls. Exp Brain Res. 1982;46:324–330.
[84] Peterson BW, Coulter JD. A new long spinal projection
from the vestibular nuclei in the cat. Brain Res. 1977;
122:351–356.
[85] Wilson VJ, Ezure K, Timerick SJ. Tonic neck reflex of
the decerebrate cat: response of spinal interneurons to
natural stimulation of neck and vestibular receptors.
J Neurophysiol. 1984;51:567–577.
[86] Keshner EA, Cohen H. Current concepts of the vestibular
system reviewed: 1. The role of the vestibulospinal system
in postural control. Am J Occup Ther. 1989;43:320–330.
[87] Bilotto G, Goldberg J, Peterson BW, et al. Dynamic
properties of vestibular reflexes in the decerebrate cat.
Exp Brain Res. 1982;47:343–352.
[88] Matsuyama K, Drew T. Vestibulospinal and reticulo­
spinal neuronal activity during locomotion in the
intact cat. I. Walking on a level surface. J Neurophysiol.
2000;84:2237–2256.
[89] Matsuyama K, Drew T. Vestibulospinal and reticulospinal
neuronal activity during locomotion in the intact
cat. II. Walking on an inclined plane. J Neurophysiol.
2000;84:2257–2276.
20  K. TAKAKUSAKI ET AL.
[90] Garcia-Rill E, Simon C, Smith K, et al. The
pedunculopontine tegmental nucleus: from basic
neuroscience to neurosurgical applications: arousal
from slices to humans: implications for DBS. J Neural
Transm. 2011;118:1397–1407.
[91] Pahapill PA, Lozano AM. The pedunculopontine nucleus
and Parkinson’s disease. Brain. 2000;123:1767–1783.
[92] Grillner S, Georgopoulos AP, Jordan LM. Selection and
initiation of motor behavior. In: Stein PSG, et al., editors.
Neurons, networks, and motor behavior. Cambridge,
MA: MIT Press; 1997. p. 3–19.
[93] Grillner S. human locomotor circuits conform. Science.
2011;334:912–913.
[94] Sherman D, Fuller PM, Marcus J, et al. Anatomical
location of the mesencephalic locomotor region and
its possible role in locomotion, posture, cataplexy, and
parkinsonism. Front Neurol. 2015;6:140.
[95] Roseberry TK, Lee AM, Lalive AL, et al. Cell-type-
specific control of brainstem locomotor circuits by basal
ganglia. Cell. 2016;164:526–537.
[96] Rossignol S, Dubuc R, Gossard JP. Dynamic
sensorimotor interactions in locomotion. Physiol Rev.
2006;86:89–154.
[97] Rossignol S, Barrière G, Frigon A, et al. Plasticity of
locomotor sensorimotor interactions after peripheral
and/or spinal lesions. Brain Res Rev. 2008;57:228–240.
[98] Fung SJ, Barnes CD. Evidence of facilitatory
coerulospinal action in lumbar motoneurons of cats.
Brain Res. 1981;216:299–311.
[99] Sakai M, Matsunaga M, Kubota A, et al. Reduction
in excessive muscle tone by selective depletion of
serotonin in intercollicularly decerebrated rats. Brain
Res. 2000;860:104–111.
[100] Takakusaki K, Kohyama J, Matsuyama K. Medullary
reticulospinal tract mediating a generalized motor
inhibition in cats: III. functional organization of
spinal interneurons in the lower lumbar segments.
Neuroscience. 2003;121:731–746.
[101] Chan SH, Barnes CD. Postsynaptic effects evoked from
brain stem reticular formation in lumbar cord and their
temporal correlations with a presynaptic mechanism.
Arch Ital Biol. 1974;112:81–97.
[102] 
Takakusaki K. Pre- and post-synaptic inhibitory
mechanisms acting on lumber spinal cord neurons during
generalized motor inhibition induced by stimulating the
medullary reticular formation in the decerebrate cat. Soc
Neuroci Abstr. 2015; Control No: 5113.
[103] Bouvier J, Caggiano V, Leiras R, et al. Descending
command neurons in the brainstem that halt
locomotion. Cell. 2015;163:1191–1203.
[104] Mortimer EM, Akert K. Cortical control and
representation of fusimotor neurons. Am J Phys Med.
1961;40:228–248.
[105] Grigg P, Preston JB. Baboon flexor and extensor
fusimotor neurons and their modulation by motor
cortex. J Neurophysiol. 1971;34:428–436.
[106] Grillner S, Hongo T, Lund S. Descending Monosynaptic
and Reflex Control of γ-Motoneurones. Acta Physiol
Scand. 1969;75:592–613.
[107] Kato M, Tanji J. The effects of electrical stimulation of
deiters' nucleus upon hindlimb γ-motoneurons in the
cat. Brain Res. 1971;30:385–395.
[108] Jankowska E. Interneuronal relay in spinal pathways
from proprioceptors. Prog Neurobiol. 1992;38:335–378.
[109] Baldissera F, Hultborn H, Illert M. Integration of spinal
neuronal systems. In: Brooks VB, editor. The nervous
system I. Bethesda, ML: Am Physiol Soc Press; 1981.
p. 509–595.
[110] Boothe DL, Cohen AH, Troyer TW. Phase locking
asymmetries at flexor-extensor transitions during fictive
locomotion. PLoS ONE. 2013;8:e64421.
[111] McCrea DA, Rybak IA. Organization of mammalian
locomotor rhythm and pattern generation. Brain Res
Rev. 2008;57:134–146.
[112] Matsuyama K, Takakusaki K. Organizing principles of
axonal projections of the long descending reticulospinal
pathway and its target spinal lamina VIII commissural
neurons: with special reference to the locomotor
function. In: Westland TB, Calton RN, editors.
Handbook on white matter: structure, function and
changes, Chapter XVIII. New York, NY: Nova Science
Publishing; 2009. p. 335–356.
[113] Pearson KG. Generating the walking gait: role of sensory
feedback. Prog Brain Res. 2003;143:123–129.
[114] Frigon A, Sirois J, Gossard JP. Effects of ankle and hip
muscle afferent inputs on rhythm generation during
fictive locomotion. J Neurophysiol. 2010;103:1591–
1605.
[115] Forssberg H. Stumbling corrective reaction: a phase
dependent compensatory reaction during locomotion.
J Neurophysiol. 1979;42:936–953.
[116] Maurer C, Mergner T, Peterka RJ. Multisensory control
of human upright stance. Exp Brain Res. 2006;171:231–
250.
[117] Mergner T, Becker W. A modeling approach to the
human spatial orientation system. Ann N Y Acad Sci.
2003;1004:303–315.
[118] Horak FB, Shupert CL, Dietz V, et al. Vestibular and
somatosensory contributions to responses to head
and body displacements in stance. Exp Brain Res.
1994;100:93–106.
[119] Shaikh AG, Meng H, Angelaki DE. Multiple reference
frames for motion in the primate cerebellum. J Neurosci.
2004;24:4491–4497.
[120] Barbieri G, Gissot AS, Fouque F, et al. Does
proprioception contribute to the sense of verticality?
Exp Brain Res. 2008;185:545–552.
[121] Bisdorff AR, Wolsley CJ, Anastasopoulos D, et al. The
perception of body verticality (subjective postural
vertical) in peripheral and central vestibular disorders.
Brain. 1996;119:1523–1534.
[122] Merfeld DM, Zupan L, Peterka RJ. Humans use internal
models to estimate gravity and linear acceleration.
Nature. 1999;398:615–618.
[123] Van Beuzekom AD, Van Gisbergen JA. Properties of the
internal representation of gravity inferred from spatial-
direction and body-tilt estimates. J Neurophysiol.
2000;84:11–27.
[124] Perennou DA, Mazibrada G, Chauvineau V, et al.
Lateropulsion, pushing and verticality perception
in hemisphere stroke: a causal relationship? Brain.
2008;131:2401–2413.
[125] Lopez C, Falconer CJ, Deroualle D, et al. In the
presence of others: self-location, balance control

and vestibular processing. Neurophysiol Clin.
2015;45:241–254.
[126] Akbarian S, Grüsser OJ, Guldin WO. Thalamic
connections of the vestibular cortical fields in the
squirrel monkey (Saimiri sciureus). J Comp Neurol.
1992;326:423–441.
[127] Lopez C, Blanke O. The thalamocortical vestibular
system in animals and humans. Brain Res Rev.
2011;67:119–146.
[128] Fukushima K. Corticovestibular interactions: anatomy,
electrophysiology, and functional considerations. Exp
Brain Res. 1997;117:1–16.
[129] Faugier-Grimaud S, Ventre J. Anatomic connections
of inferior parietal cortex (area 7) with subcortical
structures related to vestibulo-ocular function in
a monkey (macaca fascicularis). J Comp Neurol.
1989;280:1–14.
[130] Guldin WO, Grüsser OJ. Is there a vestibular cortex?
Trends Neurosci. 1998;21:254–259.
[131] Brandt T, Dieterich M. The vestibular cortex: its
locations, functions, and disorders. Ann N Y Acad Sci.
1999;871:293–312.
[132] Sugiuchi Y, Izawa Y, Ebata S, et al. Vestibular cortical
area in the periarcuate cortex: its afferent and efferent
projections. Ann N Y Acad Sci. 2005;1039:111–123.
[133] Barra J, Marquer A, Joassin R, et al. Humans use internal
models to construct and update a sense of verticality.
Brain. 2010;133:3552–3563.
[134] Maffei V, Mazzarella E, Piras F, et al. Processing of visual
gravitational motion in the peri-sylvian cortex: evidence
from brain-damaged patients. Cortex. 2016;78:55–69.
[135] Zhang LL, Wang JQ, Qi RR, et al. Motion sickness:
current knowledge and recent advance. CNS Neurosci
Ther. 2016;22:15–24.
[136] Pérennou D, Piscicelli C, Barbieri G, et al. Measuring
verticality perception after stroke: why and how?
Neurophysiol Clin. 2014 Jan;44:25–32.
[137] Karnath HO, Dieterich M. Spatial
neglect–a vestibular disorder? Brain. 2006;129:293–305.
[138] Wilson VJ, Zarzecki P, Schor RH, et al. Cortical
influences on the vestibular nuclei of the cat. Exp Brain
Res. 1999;125:1–13.
[139] Akbarian S, Grüsser OJ, Guldin WO. Corticofugal
connections between the cerebral cortex and brainstem
vestibular nuclei in the macaque monkey. J Comp
Neurol. 1994;339:421–437.
[140] Akbarian S, Grüsser OJ, Guldin WO. Corticofugal
projections to the vestibular nuclei in squirrel monkeys:
further evidence of multiple cortical vestibular fields.
J Comp Neurol. 1993;332:89–104.
[141] Ticini LF, Klose U, Nägele T, et al. Perfusion imaging
in pusher syndrome to investigate the neural substrates
involved in controlling upright body position. PLoS
ONE. 2009;4:e5737.
[142] Pérennou D, Piscicelli C, Barbieri G, et al. Measuring
verticality perception after stroke: why and how?
Neurophysiol Clin. 2014;44:25–32.
[143] Georgopoulos AP, Grillner S. Visuomotor coordination
in reaching and locomotion. Science. 1989;245:1209–
1210.
[144] Lajoie K, Andujar JE, Pearson K, et al. Neurons in area
5 of the posterior parietal cortex in the cat contribute
ADVANCED ROBOTICS  21
to interlimb coordination during visually guided
locomotion: a role in working memory. J Neurophysiol.
2010;103:2234–2254.
[145] Marigold DS, Drew T. Contribution of cells in the
posterior parietal cortex to the planning of visually
guided locomotion in the cat: effects of temporary visual
interruption. J Neurophysiol. 2011;105:2457–2470.
[146] Vicaro DS, Martin JH, Ghez C. Specialized subregions
in the cat motor cortex: a single unit analysis in the
behaving animal. Exp Brain Res. 1983;51:351–367.
[147] Nakajima K, Mori F, Tachibana A, et al. Cortical mechanisms
for the control of bipedal locomotion in Japanese monkeys:
I. Local inactivation of the primary motor cortex (M1).
Neurosci Res. 2003;46; Suppl: 1, S156.
[148] Mori F, Nakajima K, Tachibana A, et al. Cortical
mechanisms for the control of bipedal locomotion
in Japanese monkeys: II. Local inactivation of the
supplementary motor area (SMA). Neurosci Res.
2003;46; Suppl: 1, S157.
[149] Keizer K, Kuypers HGJM. Distribution of corticospinal
neurons with collaterals to the lower brain stem reticular
formation in Monkey (Macaca fascicularis). Exp Brain
Res. 1989;74:311–318.
[150] Matsuyama K, Drew T. Organization of the projections
from the pericruciate cortex to the pontomedullary
brainstem of the cat: a study using the anterograde
tracer Phaseolus vulgaris-leucoagglutinin. J Comp
Neurol. 1997;389:617–641.
[151] Hoshi E, Tanji J. Distinctions between dorsal and ventral
premotor areas: anatomical connectivity and functional
properties. Curr Opin Neurobiol. 2007;17:234–242.
[152] Snijders AH, van de Warrenburg BP, Giladi N, et al.
Neurological gait disorders in elderly people: clinical
approach and classification. Lancet Neurol. 2007;6:63–
74.
[153] Cohen RG, Nutt JG, Horak FB. Errors in postural
preparation lead to increased choice reaction times
for step initiation in older adults. J Gerontol Ser A.
2011;66A:705–713.
[154] Stecina K, Fedirchuk B, Hultborn H. Information to
cerebellum on spinal motor networks mediated by the
dorsal spinocerebellar tract. J Physiol. 2013;591:5433–
5443.
[155] Büttner U, Glasauer S, Glonti L, et al. Multimodal signal
integration in vestibular neurons of the primate fastigial
nucleus. Ann N Y Acad Sci. 2003;1004:241–251.
[156] McCall AA, Miller DJ, Catanzaro MF, et al. Hindlimb
movement modulates the activity of rostral fastigial
nucleus neurons that process vestibular input. Exp Brain
Res. 2015;233:2411–2419.
[157] Cavdar S, Onat FY, Yananli HR, et al. Cerebellar
connections to the rostral reticular nucleus of the
thalamus in the rat. J Anat. 2002;201:485–491.
[158] Asanome M, Matsuyama K, Mori S. Augmentation of
postural muscle tone induced by the stimulation of the
descending fibers in the midline area of the cerebellar
white matter in the acute decerebrate cat. Neurosci Res.
1998;30:257–269.
[159] Llinás R. Mechanisms of supraspinal actions upon
spinal cord activities. Difference between reticular
and cerebellar inhibitory actions upon alpha extensor
motoneurons. J Neurophysiol. 1964;27:1117–1126.
22  K. TAKAKUSAKI ET AL.
[160] Eccles JC, Nicoll RA, Schwarz DWF, et al. Reticulospinal
neurons with and without monosynaptic inputs from
cerebellar nuclei. J Neurophysiol. 1975;38:513–530.
[161] 
Fukushima K, Peterson BW, Uchino Y, et al. Direct
fastigiospinal fibers in the cat. Brain Res. 1977;126:538–542.
[162] Mori S, Matsui T, Kuze B, et al. Cerebellar-induced
locomotion: reticulospinal control of spinal rhythm
generating mechanism in catsa. Ann N Y Acad Sci.
1998;860:94–105.
[163] Mori S, Matsui T, Mori F, et al. Instigation and control
of treadmill locomotion in high decerebrate cats
by stimulation of the hook bundle of Russell in the
cerebellum. Can J Physiol Pharmacol. 2000;78:945–957.
[164] Bostan AC, Dum RP, Strick PL. Cerebellar networks
with the cerebral cortex and basal ganglia. Trends Cogn
Sci. 2013;17:241–254.
[165] Sasaki K, Kawaguchi S, Oka H, et al. Electrophysiological
studies on the cerebellocerebral projections in monkeys.
Exp Brain Res. 1976;24:495–507.
[166] Amino Y, Kyuhou S, Matsuzaki R, et al. Cerebello-
thalamo-cortical projections to the posterior parietal
cortex in the macaque monkey. Neurosci Lett.
2001;309:29–32.
[167] Kyuhou S, Kawaguchi S. Cerebellocerebral projection
from the fastigial nucleus onto the frontal eye field
and anterior ectosylvian visual area in the cat. J Comp
Neurol. 1987;259:571–590.
[168] Tarnutzer AA, Marti S, Straumann D. Gravity perception
in cerebellar patients. Prog Brain Res. 2008;171:369–
372.
[169] Timmann D, Horak FB. Perturbed step initiation in
cerebellar subjects: 2. Modification of anticipatory
postural adjustments. Exp Brain Res. 2001;141:110–120.
[170] Bostan AC, Dum RP, Strick PL. The basal ganglia
communicate with the cerebellum. Proc Nat Acad Sci.
2010;107:8452–8456.
[171] Brown LL, Schneider JS, Lidsky TI. Sensory and
cognitive functions of the basal ganglia. Curr Opin
Neurobiol. 1997;7:157–163.
[172] Bloem BR, Valkenburg VV, Slabbekoorn M, et al. The
multiple tasks test. Strategies in Parkinson’s disease. Exp
Brain Res. 2001 Apr;137(3–4):478–486.
[173] Bhatia KP, Marsden CD. The behavioural and motor
consequences of focal lesions of the basal ganglia in
man. Brain. 1994;117:859–876.
[174] DeLong MR, Wichmann T. Circuits and circuit disorders
of the basal ganglia. Arch Neurol. 2007;64:20–24.
[175] Filion M, Tremblay L. Abnormal spontaneous activity
of globus pallidus neurons in monkeys with MPTP-
induced parkinsonism. Brain Res. 1991;547:142–151.
[176] Nambu A. Seven problems on the basal ganglia. Curr
Opin Neurobiol. 2008;18:595–604.
[177] Bohnen NI, Albin RL. The cholinergic system and
Parkinson disease. Behav Brain Res. 2011;221:564–573.
[178] Hirsch EC, Graybiel AM, Duyckaerts C, et al. Neuronal
loss in the pedunculopontine tegmental nucleus in
Parkinson disease and in progressive supranuclear palsy.
Proc Nat Acad Sci. 1987;84:5976–5980.
[179] Jellinger K. The pedunculopontine nucleus in
Parkinson’s disease, progressive supranuclear palsy and
Alzheimer’s disease. J Neurol, Neurosurg Psychiatry.
1988;51:540–543.
[180] Zweig RM, Jankel WR, Hedreen JC, et al. The
pedunculopontine nucleus in Parkinson’s disease. Ann
Neurol. 1989;26:41–46.
[181] Jones BE. From waking to sleeping: neuronal and
chemical substrates. Trends Pharmacol Sci. 2005;26:578–
586.
[182] Steriade M, McCormick DA, Sejnowski TJ.
Thalamocortical oscillations in the sleeping and aroused
brain. Science. 1993;262:679–685.
[183] Winn P. Experimental studies of pedunculopontine
functions: are they motor, sensory or integrative?
Parkinsonism Relat Disord. 2008;14; Suppl: 2, S194–S198.
[184] Dautan D, Huerta-Ocampo I, Witten IB, et al. A
Major external source of cholinergic innervation of
the striatum and nucleus accumbens originates in the
brainstem. J Neurosci. 2014;34:4509–4518.
[185] Mena-Segovia J, Winn P, Bolam JP. Cholinergic
modulation of midbrain dopaminergic systems. Brain
Res Rev. 2008;58:265–271.
[186] Takakusaki K, Shiroyama T, Yamamoto T, et al.
Cholinergic and noncholinergic tegmental pedunculo­
pontine projection neurons in rats revealed by
intracellular labeling. J Comp Neurol. 1996;371:
345–361.
[187] Hasselmo ME, Sarter M. Modes and models of
forebrain cholinergic neuromodulation of cognition.
Neuropsychopharmacology. 2011;36:52–73.
[188] Hanakawa T, Katsumi Y, Fukuyama H, et al. Mechanisms
underlying gait disturbance in Parkinson’s disease: a
single photon emission computed tomography study.
Brain. 1999;122:1271–1282.
[189] Bohnen NI, Müller ML, Koeppe RA, et al. History of
falls in Parkinson disease is associated with reduced
cholinergic activity. Neurology. 2009;73:1670–1676.
[190] Müller ML, Albin RL, Kotagal V, et al. Thalamic cholinergic
innervation and postural sensory integration function in
Parkinson’s disease. Brain. 2013;136:3282–3289.
[191] Müller ML, Bohnen NI. Cholinergic dysfunction
in Parkinson’s disease. Curr Neurol Neurosci Rep.
2013;13:377.
[192] Scocco DH, Wagner JN, Racosta J, et al. Subjective visual
vertical in Pisa syndrome. Parkinsonism Relat Disord.
2014;20:878–883.
[193] Vitale C, Marcelli V, Furia T, et al. Vestibular impairment
and adaptive postural imbalance in parkinsonian
patients with lateral trunk flexion. Mov Disord.
2011;26:1458–1463.
[194] Villarejo A, Camacho A, García-Ramos R, et al.
Cholinergic–Dopaminergic imbalance in pisa
syndrome. Clin Neuropharmacol. 2003;26:119–121.
[195] Doherty KM, van de Warrenburg BP, Peralta MC, et al.
Postural deformities in Parkinson’s disease. Lancet
Neurol. 2011;10:538–549.
[196] Vaugoyeau M, Azulay JP. Role of sensory information
in the control of postural orientation in Parkinson’s
disease. J Neurol Sci. 2010;289:66–68.
[197] Vaugoyeau M, Viel S, Assaiante C, et al. Impaired vertical
postural control and proprioceptive integration deficits
in Parkinson’s disease. Neuroscience. 2007;146:852–863.
[198] Pollak L, Prohorov T, Kushnir M, et al. Vestibulocervical
reflexes in idiopathic Parkinson disease. Neurophysiol
Clin. 2009;39:235–240.

[199] Michel SF, Oscar AC, Correa TE, et al. Pisa syndrome.
Clin Neuropharmacol. 2015;38:135–140.
[200] Solla P, Cannas A, Congia S, et al. Levodopa/carbidopa/
entacapone-induced acute Pisa syndrome in a Parkinson’s
disease patient. J Neurol Sci. 2008;275:154–156.
[201] van de Warrenburg BP, Bhatia KP, Quinn NP. Pisa
syndrome after unilateral pallidotomy in Parkinson’s
disease: an unrecognised, delayed adverse event?
J Neurol Neurosurg Psychiatry. 2007;78:329–330.
[202] Spanaki C, Zafeiris S, Plaitakis A. Levodopa-aggravated
lateral flexion of the neck and trunk as a delayed
phenomenon of unilateral pallidotomy. Mov Disord.
2010;25:655–656.
[203] Jacobs JV, Lou JS, Kraakevik JA, et al. The supplementary
motor area contributes to the timing of the anticipatory
postural adjustment during step initiation in participants
with and without Parkinson's disease. Neuroscience.
2009;164:877–885.
[204] Hanakawa T, Fukuyama H, Katsumi Y, et al. Enhanced
lateral premotor activity during paradoxical gait
in Parkinson’s disease. Ann Neurol. 1999;45:329–336.
[205] Mirdamadi JL. Cerebellar role in Parkinson’s disease.
J Neurophysiol. 2016;116: 917–919. doi:http://dx.doi.
org/10.1152/jn.01132.2015.
[206] Lewis MM, Galley S, Johnson S, et al. The role of the
cerebellum in the pathophysiology of Parkinson’s
disease. Can J Neurol Sci. 2013;40:299–306.
[207] Benarroch EE. Pedunculopontine nucleus: functional
organization and clinical implications. Neurology.
2013;80:1148–1155.
ADVANCED ROBOTICS  23
[208] Hamani C, Moro E, Lozano AM. The pedunculopontine
nucleus as a target for deep brain stimulation. J Neural
Transm. 2011;118:1461–1468.
[209] Pereira EA, Nandi D, Jenkinson N, et al.
Pedunculopontine stimulation from primate to patient.
J Neural Transm. 2011;118:1453–1460.
[210] Stefani A, Lozano AM, Peppe A, et al. Bilateral deep
brain stimulation of the pedunculopontine and
subthalamic nuclei in severe Parkinson’s disease. Brain.
2007;130:1596–1607.
[211] Mazzone P, Lozano A, Stanzione P, et al. Implantation of
human pedunculopontine nucleus: a safe and clinically
relevant target in Parkinson’s disease. NeuroReport.
2005;16:1877–1881.
[212] Mazzone P, Sposato S, Insola A, et al. Stereotactic surgery
of nucleus tegmenti pedunculopontini. Br J Neurosurg.
2008;22; Suppl: 1, S33–S40.
[213] 
Ferraye MU, Debû B, Fraix V, et al. Effects of
pedunculopontine nucleus area stimulation on gait
disorders in Parkinson’s disease. Brain. 2010;133:205–214.
[214] Moro E, Hamani C, Poon YY, et al. Unilateral
pedunculopontine stimulation improves falls in
Parkinson’s disease. Brain. 2010;133:215–224.
[215] Mazzone P, Scarnati E, Garcia-Rill E. Commentary:
The pedunculopontine nucleus: clinical experience,
basic questions and future directions. J Neural Transm.
2011;118:1391–1396.