JMD 16062

REVIEW ARTICLE
https://doi.org/10.14802/jmd.16062 / J Mov Disord 2017;10(1):1-17 pISSN

2005-940X / eISSN 2093-4939
Functional ABSTRACT
Neuroanatomy
Here we argue functional neuroanatomy for
posture-gait control. Multi-sensory information
such as somatosensory, visual and vestibular
for Posture and

sensation act on various areas of the brain so that
adaptable posture-gait control can be achieved.
Automatic process of gait, which is steady-state
Gait Control
stepping movements associating with postural
reflexes including head- eye coordination
accompanied by appropriate align- ment of body
segments and optimal level of postural muscle
tone, is mediated by the descending pathways
from the brainstem to the spinal cord. Par- ticularly,
Kaoru Takakusaki reticulospinal pathways arising from the lateral
The Research Center for Brain Function and Medical Engineering, part of the mesopontine tegmentum and spinal
Asahikawa Medical University, Asahikawa, Japan locomotor network contribute to this process.
On the other hand, walking in unfamiliar
circumstance requires cognitive process of
postural control, which depends on knowledges
of self-body, such as body schema and body
motion in space. The cognitive information is
produced at the temporoparietal association
cortex, and is fundamental to sustention of
vertical posture and construction of motor
programs. The programs in the motor cortical
areas run to ex- ecute anticipatory postural
adjustment that is optimal for achievement of
goal-directed movements. The basal ganglia and
cerebellum may affect both the automatic and
cognitive processes of posture- gait control
through reciprocal connections with the brainstem
and cerebral cortex, respectively. Conse- quently,
impairments in cognitive function by dam- ages in
the cerebral cortex, basal ganglia and cerebellum
may disturb posture-gait control, resulting in
falling.
Key Words
Multisensory information;
midbrain locomotor region; reticulospinal system;
body schema; motor programs;
Parkinson’s disease.
Received: December 13, 2016 Accepted: December 15, 2016
Corresponding author: Kaoru Takakusaki, MD, PhD, The Research Center for Brain Function and
Medical Engineering, Asahikawa Medical University, 2-1, 1-1 Midorigaoka- Higashi, Asahikawa
078-8511, Japan
Tel: +81-166-68-2884 Fax: +81-166-68-2887 E-mail: kusaki@asahikawa-med.ac.jp
cc This is an Open Access article distributed under the terms of the Creative Commons
Attri- bution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0)

which permits unrestricted non-commercial use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Copyright © 2017 The Korean Movement Disorder Society 1

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J Mov Disord 2017;10(1):1-
GENERAL SCHEMA OF emotional, goal-directed behaviors are always

POSTURE-GAIT CONTROL accompanied by automatic process of postural
control including balance adjustment and muscle
Figure 1 illustrates our recent understanding
tone regulation. The subject is largely unaware of
of basic signal flows involved in motor control.
this process which is evoked by sequential
Senso- ry signals arising from external stimuli
activations of neurons in the brainstem and spinal
and/or internal visceral information have various
cord. Basic locomotor motor pattern is generated
functions. For example, they are to be utilized for
by spinal locomotor networks that is termed as
cognitive processing such as production of
the central pattern generators (CPG). However, in
working memory which guides future behavior.
order to learn motor skills or behave in
Alternatively, they may affect emotional and
unfamiliar circumstance, the subject requires
arousal states. Sensory signals are further
cognitive posture-gait control that depends on
available to detect and correct postural instability
cognition of self-body information together
by acting on the cerebral cortex, cerebellum, and
with spatial localization of objects in extra-personal
brainstem. Accordingly, animal initiates
space. The cerebellum regulates the cognitive and
movements depending on either a “cognitive
automatic processes of posture-gait control by
reference” or an “emotional reference”.1,2
acting on the cerebral cortex via the
Voluntary movements are derived from
thalamocortical projection and on the brainstem,
intention- ally-elicited motor commands arising
respectively. Both the feed- forward information
from the cerebral cortex to the brainstem and
from the cerebral cortex via the cortico-ponto-
spinal cord. On the other hand, emotional
cerebellar pathway and real-time sensory
reference may contribute to emotional motor
feedback via the spinocerebellar tract to the cer-
behavior which is generated by the projections
ebellum may play major roles in these
from the limbic-hypothalamus to the brainstem,
operations. The basal ganglia may also contribute
such as fight or flight reactions.1,3,4 Re- gardless
to the modu- lation of each process though its
of whether the initiation is volitional or
gamma-aminobu- tyric acid (GABA)-ergic
projections to the cerebral cortex and
2,5,6
brainstem. The degree of GABAergic influence
from the basal ganglia is regulated by the
midbrain dopaminergic neurons.7
BRAINSTEM AND SPINAL

CORD; CORE-STRUCTURES OF
POSTURE-GAIT CONTROL
In the absence of their forebrain, like a
decerebrate cat, it can walk, trot and gallop.
When the de- cerebration is made at precollicular-
postmammilla- ry level, the cat initiates
locomotion by electrical or chemical stimulation
applied to the mesencephalic or midbrain
locomotor region (MLR).1,8,9 However, if the
Figure 1. Basic signal flow involved in postural control. Multisensory signals from
the visual, vestibular, auditory, somatosensory (proprioceptive), and visceral
neuraxis is transected slightly higher at the
receptors act on various sites in the central nervous system. These signals may precollicular-premammillary level, cats can
provide cognitive and emotional references to the cerebral cortex and limbic system, sponta- neously elicit locomotion with well-
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 coordinated postural control.10 Therefore, a
control, such regulation of postural muscle tone and basic postural reflexes, by the critical region exists between these decerebrate
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 levels. This area is recognized as the subthalamic
circumstance. See text for detail explanation. Modified from Takakusaki. Mov Disord locomotor region (SLR), which mostly
2013;28:1483-1491, with permission of Wiley.6
corresponds to the lateral hypothalamic area.
Stimulation of the SLR evoked locomotion after
2
Posture-Gait
11
Control
a large lesion was made in the MLR area, indicating that the SLR has
direct connections with the brainstem locomotor pathway beyond the
MLR. Howev-
Copyright © 2017 The Korean Movement Disorder Society 3

Posture-Gait
Control
er, the walking in the decerebrate preparations locomotor pattern, and do this by effects at the pontine level.15,18
is machine-like and is neither goal-directed nor Studies in
adaptive to the environment. Hence, the SLR
connections to the MLR are likely important
for normal control of posture and gait.
So far three locomotor regions have been
identi- fied in animals: the MLR in the
mesopontine tegmentum, the SLR and the
cerebellar locomotor region (CLR) in the mid-part
of the cerebellum.12 Human imaging study
demonstrated that the organization of these
supraspinal locomotor centers was preserved
during the transition to bipedal locomotion
human.13 The clinical relevance of these centers has
so far been largely neglected.
Role of the mesencephalic area in the

control of posture and locomotion
The MLR appears to be present in all classes
of vertebrates.14 It likely includes the cuneiform
nucleus (CNF) and the pedunculopontine
tegmental nucleus (PPN), although the precise
location of the locomotor regulation still remains
a matter of debate. 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.15 Different
neuronal types within the PPN area may have
different functions with their own inter-con-
nections to multiple parts of the brain. There are
connections to cerebral cortex, multiple basal
ganglia and limbic areas, the thalamus, the
brainstem, the spinal cord and the cerebellum.16
This key location including multiple segregate
functions, renders figur- ing out the precise
function of these regions quite complicated.17
In the experiments using decerebrate cats,
activation of neurons in the PPN suppress
muscle tone via its cholinergic projections to the
pontine reticular formation (PRF), while
activation of neurons in the CNF mostly elicits
locomotion.5,15,18-20 Microstimu- lation of the
transition zone between the two areas induced a
mixture of locomotor rhythm with associated
muscle tone suppression (Figure 2). More- over,
blocking the PRF by injecting atropine sulfate,
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
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J Mov Disord 2017;10(1):1-
rats by Sherman et al.21 neously evoked locomotion in high-
show non-cholinergic neu- decerebrated preparation, RSNs located in both
rons just medial to the PPN the dorsomedial and ventromedial PMRF were
have projections to the modulated in response to step cycles (Figure 3Ac),
spinal cord, while the indicating that muscle tone-related RSNs
cholinergic neurons of the participate in the execution of locomotion so that
PPN do not. This area at the locomotor rhythm and muscle tone can be
mesopontine junction may simultaneously regulated by the reticulospinal
be the true MLR. The dorsal system during locomotion.
neurons of this MLR area Presence of such an organization was
(laterodorsal tegmental supported by experiments using microstimulation
nucleus) with spinal projec- applied to the PMRF (Figure 3B). Stimulation
tions are active in applied to the dorsomedial part of the PMRF
locomotion, while the resulted in general suppression of muscle tone
ventral neurons are active (Figure 3B, red areas), and those applied to the
in standing and do not have ventromedial PMRF induced general
spinal projections. augmentation of muscle tone (Figure 3B, blue
areas). Neuroanatomical studies revealed that
Functional RSNs in the dorsomedial and ventromedial
organization of the PMRF descend through ventral and lateral
reticular formation funiculi, indicating that the ventral and lateral
in the control of RST are responsible for muscle tone
posture suppression and augmentation, respectively. On
It is generally agreed that the other hand, tegmental reflex, or asymmetrical
the reticulospinal tract postural figures, which was
(RST) contributes to
regulation of the level of
muscle tone. There may
exist functional organization
in the pontomedullary
reticular formation (PMRF)
in relation to the control of
postural muscle tone (Fig-
ure 3).15 Direct recording of
reticulospinal neurons
(RSNs) revealed that those
located in the dorso-me-
dial part of the PMRF are
active during the period of
muscle tone suppression or
muscular atonia (Fig- ure
3Aa), and those in the
ventromedial part are ac-
tive during reflex standing
due to decerebrate rigidity or
hypertonus (Figure 3Ab).
Accordingly, functional
topographical organization
may exist in the PMRF in
the control of postural
muscle tone. On the other
hand, during MLR-elicited
locomotion or sponta-
4
Posture-Gait
Control
characterized by extension of the unilateral limb

scending fibers within the spinal cord with the
and flexion of the contralateral limb, was evoked
RST.22,23 Matsuyama and Drew24,25 examined firing
from the area between the inhibitory and
property of neurons in the RST and VST in the
excitatory areas and the lateral part of the PMRF
cat during locomotion on an inclined surface.
where few RSNs arise in the cat (Figure 3B,
Specifically, the VST controls primarily the overall
green areas).
level of postural muscle tone, while the RST has an
In addition to the RST, vestibulospinal tract
additional role in deter- mining the relative level of
(VST) plays an important role in the control of
different muscles, particularly when the pattern is
postural equilibrium by its similar architectonic
asymmetric.
organization of de-
A Stimulation sites B Stimulation effects
Dorsal CNF
Ventral CNF
Dorsal PPN
P 2.0
PPN
Soleus EMG; L
C Effective sites Soleus EMG; R
PPN
Ventral PPN
NRPo
HypertoniaMixtureAtonia LocomotionHypotonia
10 sec
30 μA, 50 Hz, 10 sec
Figure 2. Effects of midbrain stimulation on posture and locomotion in decerebrate cat preparation. A: Stimulation sites in
the right mesopontine tegmentum. Stimulation consists of 30 μA in intensity and 50 Hz in frequency with a du- ration of 10
seconds. B: Effects of stimulation applied to each site in (A) on left and right soleus muscle electromyo- grams. Stimulation
of the dorsal part of the CNF induced muscle tone augmentation. While stimulation of the ventral CNF and the dorsal PPN
induced locomotor rhythm, the latter was accompanied by a decrease in muscle tone. Stim- ulation of the PPN and PRF
corresponding to the nucleus reticularis pontis oralis (NRPo) immediately suppressed soleus muscle activities. C:
Topography of stimulus effects in the mesopontine tegmentum. Locomotion was evoked by stimulating the CNF (blue).
Stimulation of the locus coeruleus (LC) and dorsolateral CNF induced hypertonia (violet; muscle tone augmentation).
Ventrolateral part of the PPN and NRPo, induced muscular atonia (red) and hypotonia (orange). Stimuli applied to the
locomotion-evoking sites and atonia-evoking sites elicited a mixture of rhythmic limb movements and muscle tone
suppression (green). Modified from Takakusaki et al. J Neural Transm (Vienna) 2016;123:695-729, with permission of
Springer.15 CNF: cuneiform nucleus, PPN: pedunculopontine tegmental nucleus, IC: inferior colliculus, SCP: superior cerebellar
peduncle.
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J Mov Disord 2017;10(1):1-
Locomotor pathway and its control by

hibitory projection from the GABAergic SNr to
the forebrain structures
the dorsal MLR regulates locomotion.21 In
In the “locomotor pathway”, signals from the
Parkinson’s disease (PD), GABAergic outputs of
MLR also activate medullary RSNs, in turn
the basal ganglia are abnormally increased,7 so
commanding the spinal locomotor network to
excessive SNr-inhibition of the MLR may cause
generate the oscil- latory pattern of locomotion.8,26
gait disturbance and muscle rigidity.5,18
However, the SLR and CLR may also activate
However, it is unknown whether these
this reticulospinal locomotor pathway through
mechanisms are the same for bipedal humans
distinct and direct projections.27 Signals from the
and quadru- pedal animals. It is also unclear what
MLR may also activate mono- aminergic
drives or dic- tates the SNr-induced control of
descending pathways including the coerulospinal
movements. There are sub-compartments in the
and raphespinal tracts, acting as a muscle tone
basal ganglia; neostri- atum-dorsal pallidal
excitatory system.28-30 Then we focus on the inputs
pathway (“dorsal pathway”, Figure 4A) and
of the forebrain structures to the midbrain
ventral striatum-ventral pallidal pathway (“ventral
MLR/PPN area. In decerebrate cats, the basal
pathway”, Figure 4B). The nucleus accumbens, as
ganglia control locomotion and posture using
a component of the limbic system, may be
different GABAergic output pathways of the
important in releasing locomotion, via GABAer-
substantia nigra reticulata (SNr); the lateral part
gic projections disinhibiting the MLR via the
of the SNr blocks the PPN- induced muscle tone
ventral pallidum32,33 and via fibers to the SNr
suppression, whereas the medial part of the SNr
(Figure 4B).34 Because the nucleus accumbens also
suppresses the MLR-induced locomotion.18,20,31
receives inputs from the hippocampus and
Recent rat studies confirm that inhibitory input
amygdala, the ventral pathway may be implicated
from the SNc (GABAergic and dopaminergic)
in reward-oriented locomotor behaviors, as it
to ventral MLR regulate posture, while in-
receives inputs from ventral
A Location of medullary reticulospinal neurons B Changes in postural muscle tone
a. Suppression-relatedb. Hypertonus-relatedc. Locomotion-modulated
P 6.0
P 9.0
Suppression
80-100% 60%
P 9.0 Augmentation
80-100% 60%
P 10.0 Tegmental reflexes 80-100% 60%
Figure 3. Functional organization of medullary reticulospinal systems in decerebrate cats. A: Locations of the medullary reticulospinal neurons
relating to muscle tone suppression (a), muscle tone augmentation (hypertonus) (b), and locomotion (c). During reflex standing of the decerebrate
cats, reticulospinal neurons with a firing frequency more than 10 Hz during reflex standing of decerebrate cats are judged as hypertonus-related
reticulospinal neurons (b; n = 76). When carbachol (long-acting cholinomimetic agents) was injected into the pontine reticular formation muscle tone
of decerebrate cats was abolished. Reticulospinal neurons of which firing frequency was increased to more than 10 Hz during carbachol-induced
atonia are judged as atonia-related reticulospinal neurons (a; n = 75). During reflex standing (decerebrate rigidity) these cells usually had no
spontaneous firing. Locomotion-related neurons (n = 59) were judged as those displaying rhythmic firing relating to step cycles of locomotion.
Recording was made in both high decerebrated cats which displayed spontaneous locomotion and normal decerebrated cats with stimulation of the
MLR. B: Results obtained from five animals are superimposed on representative coro- nal planes of the 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. Modified from Takakusaki et al. J Neural Transm (Vienna) 2016;123:695-729, with
permission of Springer.15 P: pyramidal tract, MLF: medial longitudinal fasciculus, 5ST: spinal trigeminal tract, NRPc: nucleus reticularis pontis caudalis, TB:
trapezoid body, RM: nucleus raphe magnus, SO: superior olive, NRGc: nucleus reticularis gigantocellularis, NRMc: nucleus reticularis magnocellularis, RPa:
nucleus raphe pallidus, NRPv: nucleus reticulars parvocellularis.
6
Posture-Gait
Control
tegmental area, hippocampus and amygdala. On

Spinal control of posture and gait
the other hand, the more recently evolved parts
Spinal circuitry involved in the stretch reflex, re-
of the basal ganglia make up the dorsal system
ciprocal inhibition, non-reciprocal inhibition (or
(Figure 4A).35 These parts may achieve locomotor
au- togenic inhibition) and flexion reflexes are
control depending on cognitive behavioral
involved in the control of posture. Particularly,
context, such as sensory- guided locomotor
stretch reflex and non-reciprocal inhibition (Ib
control.
inhibition) play major role in static control of
posture. On the other hand, interneuronal
networks involved in reciprocal Ia in-
Excitatory system Inhibitory system Locomotor pathway
Spinal locomotor network
Primary
B afferents
Muscles
Inhibitory interneuronsMotoneurons Excitatory system

Inhibitory system Locomotor pathway
Spinal locomotor network
Primary
afferents
Muscles
Inhibitory interneuronsMotoneurons
Figure 4. Neuronal mechanisms of cognitive (A) and emotional (B) control of locomotion in the cat. A: Dorsal system for
cognitive locomotor control. A visuo-motor pathway from the visual cortex to motor cortex via the parietal cortex
contributes to this control. Corticofugal projections act on to the basal ganglia nuclei, brainstem and spinal cord.
Dopaminergic projection from the substantia nigra pars compacta (SNc) to the caudate-putamen (CPu) may be involved in
learning the locomotor behaviors. GABAergic output from the basal ganglia nuclei (internal segment of the globus pallidus
and substantia nigra pars reticulata; GPi/SNr) acts on MLR/PPN area may control locomotion and posture. Efferents from
the midbrain locomotor region (MLR) recruit excitatory system, inhibitory system and locomotor pathway. The excitatory
system arises from the LC and the raphe nuclei. The inhibitory system which arises from cholinergic neurons in the PPN
sequentially activates PRF neurons, medullary reticulospinal neurons in the nucleus reticularis gigantocellularis (NRGc) and
spinal inhibitory interneurons. The inhibitory interneurons may inhibit both motoneurons and interneurons. The locomotor
pathway consists of reticulospinal neurons arising from the ventromedial medulla corresponding to the nucleus reticularis
magnocellularis (NRMc). Cholinergic and gluta- matergic projections from the PPN excite SNc-DA neurons. These
descending tracts act on CPGs in spinal cord so that muscle tone and locomotion are regulated. Efferents from the (CLR
may excite locomotor pathway. B: Ventral system for emotional locomotor control. Efferents from the amygdala (AMD)
and hippocampus (Hipp) project to the nucleus accumbens (NAc). GABAergic NAc neurons project to ventral pallidum
(VP) and the SNr, which control activity of the MLR/PPN neurons. Efferents from the AMD and the Hipp also act on
lateral hypothalamic area, which corresponds to the SLR. DA projections from the ventral tegmental area (VTA) may
contribute to the reward- oriented locomotor behaviors. Modified from Snijders et al. Ann Neurol 2016;80:644-659, with
permission of Wi- ley.164 E: extensor motoneurons, F: flexor motoneurons, PRF: pontine reticular formation, PPN:
pedunculopontine tegmental nucleus, LC: locus coeruleus, RN: raphe nuclei, DA: dopamine, CLR: cerebellar locomotor
region, SLR: subthalamic locomotor region, CNF: cuneiform nucleus, CTX: cortex, GPe: external segment of the globus
pallidus.
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hibition and flexion reflexes including crossed- phase. Afferents from proprioceptors in extensor muscles regulate
extension reflex and are critical to produce transition from stance to swing phase. It should be critically noted that
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 movement. 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. Be- cause spinal 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,36,37 and integration of descending
supraspinal signals and peripheral sensory
afferents at the level of spinal cord is necessary for
full execution of postural control.
Organization of the spinal locomotor network

Once animals start locomotion, muscle tone
must be regulated depending on locomotor cycles.
A par- ticular group of spinal interneuronal
networks that generates rhythmic activity in the
absence of rhythmic inputs is termed CPG.1,36,37
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.26,38 The signals are then transmitted to
the target motoneurons innervating ipsilateral limb
muscles through their excitatory and inhibitory
actions.26,36 Reciprocal Ia interneurons, classical Ib in-
terneurons and Renshaw cells are likely included
in this group.36 On the other hand, lamina VIII
interneurons projecting to the contralateral side
contribute to the left-right alternations of limb
movements.39,40 The rhythm and pattern 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.36
Spinal control of muscle tone

during locomotion
Activity of the spinal locomotor networks is
modulated by sensory afferents in a phase
dependent manner.36,38,41,42 For example,
proprioceptors in muscles at the hip joint are
primarily responsible for reg- ulating the stance
8
Posture-Gait
Control
signals in Ib afferents from fool, and were able to remember the location of
tendon organ in ankle ex- food. They utilized the visual and haptic senses
tensor muscles inhibit with respect to external space. However, in the
homonymous motoneurons adult cats, skilled locomotor performance was
at rest, while they excite disturbed when lesions were made in the motor-
extensor motoneurons dur- related cortical regions.45 If the caudate nucleus of
ing stance phase.36,41 The the cat is selectively removed both sides,46 a
functional consequence of remarkable behavior develops referred to as the
this “reflex reversal” is that “compulsory approaching syndrome”. The cat
the swing phase is not ini- faithfully followed any moving object that catches
tiated until the extensor its attention, seemingly unable to terminate the
muscles are unloaded and locomotor behavior. This was referred to as
the forces exerted by these “visually-determined cortical automatism”.47 The
muscles are low. main manifesta- tions consisted of loss of drive
Skin afferents also exert a (apathy), obsessive- compulsive behavior,
powerful influence on the cognitive deficits, stimulus- bound perseverative
CPG.26,36,41 Skin receptors are behavior, and hyperactivity.46 On the other hand,
important to detect obstacles removal of both the cerebral cortex and the
and adjust stepping to avoid striatum (diencephalic cat; the thalamus and
them such as the “stumble- hypothalamus were preserved) resulted in the
corrective reaction.43 cats walking incessantly, even though they did not
Importantly, the corrective attend to any environmental stimuli.48
flexion movements are Forebrain structure including the cerebral cortex,
produced only if the paw is
stimulated during the
swing phase. An identical
stimulus applied during
stance phase elicits the
opposite response, an
excitation of extensor mus-
cles that reinforces the
ongoing extensor activity.
This is another example of
the reflex reversal. The
reflex reversal phenomenon
is critically involved in
postural control during
locomotion. However, its
mechanisms have not been
elucidated.
HIGHER-ORDER
REGULATION OF
POSTURE-GAIT
CONTROL
Classical lesion studies in the cat
Even cerebral cortex was
removed, the kitten can
alive more than several
years.44 They could eat and
exhibit periods of rest,
become active, search for
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the limbic-hypothalamic structures, and the

Control by the cerebral cortex
basal ganglia as well as the cerebellum control
posture and gait largely by acting on the
While basic locomotor synergy was not
reticulospinal system through their direct and
largely disturbed if pyramidal tracts were
indirect connections via the MLR/PPN area
bilaterally discon- nected,49 skilled locomotor task
(Figure 4). These cortical and subcortical
was severely impaired. Liddell and Phillips50 found
projections may enable animals to express
after unilateral or bilateral pyramidal lesions that
volitional and emotional motor behaviors
the cats became ‘helplessly immobile’, unable to
depending on the context.2,14
take a step without slipping or falling, when they
were required to walk along a nar-
A B
Figure 5. Hypotheses of cognitive process of posture-gait control. A: Cognition 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. Reciprocal connection between the temporoparietal
cortex and cerebellum may contribute to this process. B: Transmission of the bodily information. The bodil y 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. Similarly,
the information is transferred to hippocampus and is used to navigate further behaviors. C: Motor programming. The motor cortical areas closely
cooperate with the basal ganglia and cerebellum so that appropriate motor programs are constructed. D: 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. Signals from the prefrontal cortex including plans and intentions may trigger to run motor programs in the
SMA/PM, which 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 the M1 so that goal-directed
purposeful skilled movements can be achieved. Modified from http://dx.doi.org/10.1080/01691864.2016.1252690, with permisson of Taylor &
Francis.165
1
Posture-Gait
Control
row beam or horizontal ladder. Such a skilled fulfilment of ongoing purposeful control via anticipatory adjustments of
performance became more severely damaged by posture.61 It follows that both the intentional limb move-
postcruciate than by precruciate lesions. After
postcruciate lesions including both the
somatosensory and parietal cortices, the cat refused
to walk on narrow trucks.45 The precruciate area,
which corresponds to supplementary motor area
(SMA) and premotor area (PM) of the primates,
may be involved in movement initiation. On the
other hand, the postcruciate cortices may utilize
specific somatosensory inputs to fulfil a role in the
regulation of ongoing movements51 in the manner
of anticipatory or feed-forward adjustments.52 Skilled
posture-gait control, therefore, can be achieved on
the basis of knowledges of the orientation and
motion of the body in space as well as motion
perception and spatial localization of objects in
extra-personal space.53-55 Such a knowledge is
provided by integration of vestibular,
somatosensory and visual sensory signals which
occurs at both the cerebral cortex and cerebellum
(Figure 5A).56
Precise visuomotor coordination occurred at the
cerebral cortex plays critical roles in the execution
of precise arm-hand movements such as reaching
and grasping.57 Similarly, when a walking subject
encounters obstacles, each leg must be placed
with a high degree of accuracy through the
visuo-parieto-frontal cortical projection, as in the
subject has to modify the leg trajectory in each
step in order to achieve appropriate foot
placement.58 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 stepping over it. When
the posterior parietal cortex was bilaterally
removed, the cat’s hindlimbs did not step over the
obstacles if their forelimbs cleared them.59
Therefore, 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 (Figure 5B) so that the cat
can precisely modify the limb trajectory.59,60 To
successfully achieve such an accurate control of
limb movements during walking, posture must be
optimized in advance to the purposeful action so
that bodily equilibrium can be maintained.
Therefore, the visuo-parieto-frontal cortical
projection (Figure 5B) is critically involved in the
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J Mov Disord 2017;10(1):1-
ments and anticipatory mans, shows that the SMA is strongly connected
postural adjustment are to the lateral PPN, while the dorsal PM is
programmed at motor cortical connected to the medial PPN.66 The RST
areas (Figure 5B and D). innervates whole spinal segments22 so that it
controls postural muscle tone and symmetric
Anticipatory postural adjustment postural figures (Figure 3).15 Therefore, the cortico-
Then, what part of the reticular and RST may achieve anticipatory
motor cortex contributes to postural adjustment (Figure 5D) Possibly, the
the programming of the SMA contributes to the anticipatory postural
anticipatory postural ad- adjustment for step initiation, which is impaired in
justments? One of the most PD patients.67 On the other hand, the PM/SMA may
candidate areas is the SMA forward programs of precise leg-foot movement to
and PM (Figure 5B and C). the M1,68 which, in turn, sends motor command via
In bipedal walking the corticospinal tract. Consequently, cognitive
monkey, an inactivation of information in the temporoparietal cortex is
the leg area of the primary essential for accurate gait control particularly
motor cortex (M1) by when the subject encounters an unfamiliar
injecting muscimol environment. Therefore, the deficiency in the
(GABAA agonist) partly information processing from the temporopari-
paralyzed the contralateral etal cortex to the frontal cortex (frontoparietal
leg.62 On the other hand, network) may cause errors in anticipatory
muscimol injections into postural adjustment and gait difficulties such as
the trunk/leg regions of the the “freezing of gait”. It follows that deficits in
bilateral SMA largely cognitive function in elder persons and in patients
disturbed postural control with Alzheimer’s disease
without inducing paraly-
sis.63 When it was injected
into the dorsal PM, spon-
taneous walking was
maintained; however, the
monkey could not start
walking using sensory cue.
These findings indicate the
SMA and PM may
contribute to postural
control during bipedal
walking and initiation of
gait, respectively.
Studies using neural
tracers have demonstrated
abundant cortico-fugal
projections to the PMRF
from the premotor cortices
(SMA/PM) in quadruped64
and biped65 animals.
Recent studies have
focused onto the
importance of cortico-
pedunculopontine
projection in terms of motor
control. Probabilistic dif-
fusion tractography in rhesus
monkey as well as hu-
1
Posture-Gait
Control
are at higher risk of falling particularly when patho- physiological

more cognitive tasks are required.69,70 mechanism is operating in
Pisa syndrome.
Maintenance of vertical posture
Next critical question as to the cortical control
of posture is “how does the brain acquire access
to an internal estimate of body motion and
postural verticality?” Postural vertical is
supported by a sense of verticality which is
synthesized by visual, somatosensory and
vestibular information.71-75 Among them, the
vestibular sensation is superior to others in terms
of absoluteness of sensation because it always
refers the gravity,76 and the vestibular system
provides the brain with sensory signals about
three-dimensional head rotations and translations.
Vestibulothalamic projections are bilateral and
mainly involve the posterior thalamus.77-79 While
there was no cortical area that receives inputs
exclusively from vestibular afferents, there are
multiple presentations of vestibular information
in the cerebral cortex,80 such as the frontal eye
field, PM, somatosensory cortex, ventral intra-
parietal cortex, medial superior temporal area,
and parieto-insular vestibular cortex (PIVC). The
PIVC has particularly dense connections with
other vestibular-relating cortical areas, and
receives information from other sensory
modalities.81-83 Now, both the posterior thalamus
and PIVC are areas of interest for the internal
model of postural verticality.84-88 Because the PIVC
has descending projections to the contralateral
vestibular nuclei,79,89-91 the vestibular cortical sys-
tems possibly contribute to upright standing by
acting to the vestibulospinal system based on the
internal model of postural verticality (Figure 5B).
Postural verticality is often disturbed in
pathological conditions such as “pusher syndrome”
after stroke and “Pisa syndrome” in advanced PD.
Stroke patients with pusher syndrome actively push
away from the ipsile- sional side and have a
tendency to fall towards their paretic,
contralesional side (the left side for right-hemi-
sphere patients). They had lesions including the
parietal insular cortex or posterior
84,87,88,92
thalamus. This phenomenon is more
prominent when patients are upright compared to
when lying down. Now the pusher phenomenon
can be arising from a conflict or mismatch
between visual and postural vertical.84,87,88
However, it is still uncertain whether the same
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J Mov Disord 2017;10(1):1-
Posture-gait control by the cerebellum
Postural control by the cerebellum highly depends on sensory afferents.
Signals from the labyrinth as- cend the vestibular nerve to the floccules
and ver- mis of the cerebellum in addition to the vestibular nuclei. The
fastigial nuclei (FN) receive a copy of the output of the spinal cord in
addition to peripheral sensory information via spinocerebellar tracts.93
The FN also receive visual94 and vestibular95 information. These
multisensory features may provide “an error- correction mechanism”,
which permits FN neurons to affect motor functions such as coordinating
postural responses during walking which entail changes in limb
position. The FN may therefore send highly integrated bodily
information to the posture-gait related areas in the brainstem and motor
cortical areas.96
Action on the brainstem structures

Output from the FN to the brainstem contributes to the control of
postural muscle tone. Electrical stimulation applied to the mid-part of the
cerebellar white matter in decerebrate cats either increased97 or reduced the
level of muscle tone.98 The cerebellar stimulation possibly activated the
excitatory RST and VST of both sides 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 with- drawal of excitatory
influence upon motoneurons.98 Because, postural muscle tone is generally
reduced by the damage of the medial part of the cerebellum, the
cerebellum contributes to the activation of antigravi- ty muscles. Possibly,
the FN regulates posture-gait subprograms in the brainstem and spinal
cord by in- parallel activation of fastigio-spinal, fastigio-reticular, and
fastigio-vestibular pathways.27,99,100 Therefore, the deficiency in these
pathways may reduce the degree of α–γ linkage in patients with
cerebellar diseases, resulting in hypotonia. The hypotonia state reduces the
accuracy of the sensory feedback so that posture-gait control can be
seriously disturbed.
Cerebellar actions on the cerebral cortex

Reciprocal connections between the cerebellum and cerebral cortex
(Figure 5C) may be critically involved in the cognitive and programing
processes of postural control. More recently, it has been recognized
that cerebellar output reaches vast areas of the cerebral cortex including
prefrontal and posterior parietal cortices in addition to motor-related
areas.101
1
Posture-Gait
Control
The FN in the cerebellum, as well as the vestibular and 4) disturbances in posture-gait areas in the brainstem.15,18,113
cortex (PIVC), is critically involved in encoding
internal postural model in space and self-
motion.56 Some studies have suggested the
presence of FN projections to the parietal
cortex,102,103 motor cortex and multimodal visual
areas.104 Reciprocal connection between parietal
cortex and the cerebellum may be involved in
perception of body motion in space (Fig- ure 5B).
Such a bodily information can be utilized to
maintain upright posture during standing and to
achieve anticipatory postural adjustment. The latter
may involve reciprocal connections between the
motor cortical area (SMA/PM) and cerebellum
(motor loop) in order to construct motor programs
(Figure 5C).105,106 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.107 In addition, only few abnormalities of
anticipatory postural adjustment were found in
the cerebellar disease patients compared to
controls, while the patients appeared to be less able
to use predictive information.108 Because the
cerebellum is reciprocally connected with the basal
ganglia,109 it is possible that basal ganglia in addition
to the cerebral cortex may complement the
cerebellar role of cognitive process of postural
control.
Posture-gait control by the basal ganglia

in relation to PD
Because posture-gait control is seriously
impaired in PD, the basal ganglia has long been
functionally regarded to be predominantly
involved in motor control but is increasingly
recognized to play additional roles in sensory
processing, cognition, and behavior.110-112 Here,
emphasis has been placed on the mechanisms of
posture-gait impairment in PD so that
understanding the role of basal ganglia to the
postural control is facilitated. Based on our
recent understanding, postural disturbances in
PD attribute to following mechanisms: 1)
disturbances in the dopaminergic and cholinergic
systems, 2) impairment of cognitive functions due
to failure of integrative sensory processing that
allows to produce internal postural model (body
schema), 3) failure in motor programming due
to reduced activity in the motor cortical areas,
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J Mov Disord 2017;10(1):1-
Disturbances in processing in PD can be largely attributed to the
the dopaminergic damage of the cholinergic systems. Accordingly,
and cholinergic both of the excessive inhibition from the basal
systems ganglia and the damage of cholinergic systems
Recent clinical studies may impair both the cortical and subcortical,
suggest that the postural particularly the brainstem, functions.
impairments in PD is based
on dysfunction of both the Impairments in sensory processing
dopaminergic and and cognition
cholinergic systems. Distur- Cortical activity was substantially reduced in
bances in these patients in PD compared control subject during
chemospecific systems may walking.128,129 This may cause failure of integrative
critically contribute to sensory processing, which in turn, disturb
posture-gait failure in this construction internal postural model and motor
disease. For example, a programming. It has been shown that a loss of
damage of dopamine (DA) cholinergic neurons in the BF and PPN associates
neurons in the substantia with fallers in PD.116,130 Müller and Bohnen131
nigra pars compacta (SNc), suggested that reduced activities in the
which project to the basal cholinergic PPN neurons may disturb multi-
ganglia nuclei, is considered sensory integration at the level of the thalamus.
to increase in the This may also explain why patients in PD with
GABAergic inhibitory more severe posture-gait instability have a high
output from the basal gan- risk of de- veloping dementia.131 Impairment of the
glia.7,114,115 This may strongly integration of sensory information, particularly
inhibit thalamocortical proprioception132
systems and brainstem
structures (Figure 1).
In addition, cholinergic
neurons in the PPN (brain-
stem) and basal forebrain
(BF) are seriously dam-
aged in PD.116-119 Indeed, a
reduction of the thalamic
cholinergic innervation in
patients with PD has no
cognitive and motor
impairments but exhibits an
increase in postural sway
speed.120 Cholinergic PPN
neurons project to the non-
specific thalamocortical
system,121-123 basal ganglia
nuclei including DA neu-
rons in the SNc and
PMRF.124-126 On the other
hand, cholinergic BF
projections to the cerebral
cortex are necessary for
attentional performance and
cognitive processing.127
Therefore, disturbances in
attention, sensori-motor
integration and cognitive
1
Posture-Gait
Control
and vestibular graviception,133 may result in deficits to the decrease in

of internal model of postural verticality which is excitability of the motor
possibly constructed at the temporoparietal cortical areas in addition
association area including the vestibular cortex. to impairment of sensory
Therefore, asymmetry in the activity of the left processing
and right vestibular cortices may induce leaning
upright posture, which is often called as Pisa
syndrome. Pisa syndrome is a dystonic
lateroflexion of the trunk with a postural dis-
turbance resembling the leaning tower of Pisa, and
is more often observed in patients with
advanced PD.134 The marked lateroflexion become
worsen during walking but is almost completely
alleviated by passive mobilization or supine
positioning.135 Be- cause PD without Pisa
syndrome also had deficien- cies in postural
verticality compared to healthy controls,132,136-138
mismatch between proprioception and vestibular
gravitation in PD may alter subjective postural
verticality, resulting in Pisa syndrome. Al-
ternatively, asymmetry of the basal ganglia
output, which is due to cholinergic-dopaminergic
imbalance in the striatum134,139,140 or disturbance of
the pallidal output,141,142 may also elicit left-right
disproportion of the thalamocortical processing of
vestibular information.
Failure in motor programming

The motor cortical areas including the M1,
SMA, and PM have connections with the basal
ganglia and cerebellum, constituting motor loop
that contributes to execution and motor
programming of voluntary movements (Figure
5C).105,106 Because of increasing inhibitory output
from the basal ganglia to the thalamocortical
projections in addition to reduced cognitive
information processing, the capability of pro-
ducing motor programs in response to changes
in circumstance can be deteriorated. In fact, the
SMA contributes to the anticipatory postural
adjustment for step initiation via corticofugal
projections to the PPN and PMRF, and this
process is seriously impaired in PD patients.67
Also, the dorsal part of the PM is involved in
sensory-guided gait control as suggested in
bipedally walking monkey.62 Because the activity
of dorsal part of the PM was increased during
visually-guided paradoxical gait in PD, posture-
gait programs in SMA/PM became reusable by the
activation of visuo-motor pathway.129 According-
ly, failure in motor programming in PD can be due
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J Mov Disord 2017;10(1):1-
in the temporoparietal cortices. Recently, role of the cerebellum in the
pathophysiology of PD is highly recognized.143,144 Because the
cerebellum has reciprocal connections with the basal ganglia (Figure
5C) in addition to the cerebral cortex and brainstem, there is a need to
elucidate whether the cerebellum partici- pates in compensatory
mechanisms associated with the disease or contributes to the
pathophysiology of PD.
Reduced activity in posture-gait area in the midbrain

We propose that reduced excitability in the mesopontine tegmentum
including the PPN/MLR can be also involved in posture-gait failure in
PD.6,15,18,20,113 In decerebrate cats, the basal ganglia control locomotion and
posture using different GABAergic output pathways of the SNr; the lateral
part of the SNr blocks the PPN-induced muscle tone suppression, whereas
the medial part of the SNr suppresses the MLR-induced locomotion.18
Recent studies in rodents confirm that inhibitory input from the SNr to
the glutama- tergic neurons in the MLR regulates locomotion.21,145 In PD,
GABAergic outputs of the basal ganglia are abnormally increased,7,114 so
excessive SNr-inhibition of the MLR may cause gait disturbance and
muscle rigidity acting on MLR and muscle tone inhibitory region in the
PPN.18 Muscle tone rigidity in PD is called as “lead-pipe like rigidity”
which is characterized 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 cam- ptocormia.146
PD patients with cholinergic cell loss in the PPN showed more severe
motor disabilities with gait and posture, which were associated with L-
3,4-dihy- droxyphenylalanine (L-DOPA)-resistant akinesia.147,148 Subsequent
post-mortem study in PD patients estab- lished a correlation between the
occurrence of falls and freezing and the loss of cholinergic PPN neurons.
However, the degree of neuronal loss in the CNF was not significantly
different between fallers and non- fallers in PD patients.147 In PD
patients, individual neurons in the dorsal PPN increased their firing rates
with increased stepping frequency.149 Moreover, gait speed in PD patients
was correlated with a power of alpha-oscillations (7–10 Hz) of field
potentials re- corded from the PPN area.150
As one of clinical procedures for alleviating gait-
1
Posture-Gait
Control
posture deficiency in PD, deep brain Acknowledgments

stimulation (DBS) targeting the PPN with the aim This work is partially supported by grants from JSPS KAKEN-
of stimulating remaining cholinergic neurons.151-155
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. However, further clinical studies
concluded that freezing of gait were mildly
improved by PPN-DBS but some results were
rather disappointing.156,157 These results empha- size
the need to determine the optimal surgical tar-
get.158,159 Ferraye et al.156 suggest that the most suit-
able targets are located slightly posterior to the
PPN pars compacta, probably in the ventral part of
the CNF where stimulation-induced locomotion
has been re- ported in animals.18 This area possibly
corresponds to the subcuneiform nucleus as
described by Alam et al.160 and Karachi et al.161
also suggest that it may be the case that treating
PD patients suffering from failure of gait
initiation versus falling may require specifically
targeting the CNF and the dorsal part of the PPN,
respectively.
Reorganization of cortico-cerebello-
brainstem pathways in PD
In human, Fling et al.162 used functional
neuroimag- ing approach and revealed strong
functional connectivity between the SMA and
PPN/MLR area, which was positively correlated
with freezing severity in patients of PD. In
contrast, connectivity between the STN and SMA
was lost. They suggested that the for- mer
connectivity may potentially due to a maladap-
tive compensation, and the latter may reflect the
reduced automatic control of gait by the basal
ganglia. A study using diffusion tensor imaging
revealed the connection between the cerebellum
and the PPN in PD patients without freezing of
gait. However, freezers of patients in PD showed
the absence of cerebellotegmental connectivity
and increased visibility of the de- cussation of
corticopontine fibers in the anterior pons.163
These findings highlight the importance of
corticopontine-cerebellar pathways in the
pathophysiology of gait when the
cerebellotegmental connection that may
contribute to automatic execution of gait control
is damaged in freezers of PD.
Conflicts of Interest
The author has no financial conflicts of interest.
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JM ; ( ):
J Mov Disord 2017 10 1 1-
HI (Grant Numbers 26120004 and mesencephalon in locomotion. Arch Neur- Psych
25290001) and from Japan 1930;23:1-43.
Agency for Medical Research and 11. Shik ML, Orlovsky GN. Neurophysiology of
Development (AMED) for locomotor automatism. Physiol Rev 1976;56:465-501.
K.T. KT is also supported by 12. Mori S, Matsui T, Kuze B, Asanome M, Nakajima K,
granting foundations from the Mat- suyama K. Stimulation of a restricted region in
QOLER Medical Group and the midline cerebellar white matter evokes
Sasson Hospital. coordinated quadru- pedal locomotion in the
decerebrate cat. J Neurophysiol 1999;82:290-300.
13. Jahn K, Deutschländer A, Stephan T, Kalla R,
REFERENCES Wiesmann M, Strupp M, et al. Imaging human
1. Grillner S. Control of supraspinal locomotor centers in brainstem and
locomotion in bipeds, cerebellum. Neuroimage 2008; 39:786-792.
tetrapods, and fish. In: 14. Grillner S, Georgopoulos AP, Jordan LM. Selection
Brookhart JM, Mountcastle and initiation of motor behavior. In: Stein PSG,
VB, editors. Handbook of Grillner S, Selverston AI, Stuart DG, editors. Neurons,
physiology. The nervous networks, and motor behavior. Cambridge, MA: The MIT
system II. Bethes- da, MD: Press, 1997;3- 19.
American Physiological 15. Takakusaki K, Chiba R, Nozu T, Okumura T.
Society, 1981;1179-1236. Brainstem control of locomotion and muscle tone with
2. Takakusaki K. Forebrain special reference to the role of the mesopontine
control of locomotor tegmentum and medullary reticulospinal systems. J
behaviors. Brain Res Rev Neural Transm (Vienna) 2016;123:695-729.
2008;57:192-198. 16. Mena-Segovia J. Structural and functional considerations
3. Sinnamon HM. Preoptic and of the cholinergic brainstem. J Neural Transm
hypothalamic neurons and (Vienna) 2016;123:731-736.
the initiation of locomotion 17. Petzold A, Valencia M, Pál B, Mena-Segovia J.
in the anesthetized rat. Prog Decoding brain state transitions in the
Neurobiol 1993;41:323-344. pedunculopontine nucleus: cooperative phasic and
4. Takakusaki K, Takahashi K, tonic mechanisms. Front Neural
Saitoh K, Harada H, Okumu-
ra T, Kayama Y, et al.
Orexinergic projections to
the cat midbrain mediate
alternation of emotional
behavioural states from
locomotion to cataplexy. J
Physiol 2005;568(Pt 3):1003-
1020.
5. Takakusaki K, Tomita N,
Yano M. Substrates for
normal gait and
pathophysiology of gait
disturbances with respect to
the basal ganglia dysfunction.
J Neurol 2008;255 Suppl
4:19-29.
6. Takakusaki K.
Neurophysiology of gait:
from the spinal cord to the
frontal lobe. Mov Disord
2013;28:1483-1491.
7. DeLong MR, Wichmann T.
Circuits and circuit disorders
of the basal ganglia. Arch
Neurol 2007;64:20-24.
8. Armstrong DM. Supraspinal
contributions to the initia-
tion and control of
locomotion in the cat. Prog
Neurobiol 1986;26:273-361.
9. Mori S. Integration of
posture and locomotion in
acute decerebrate cats and in
awake, freely moving cats.
Prog Neurobiol 1987;28:161-
195.
10. Hinsey JC, Ranson SW,
McNattin RF. The role of the
hypothalamus and
2
Posture-Gait
Control
Circuits 2015;9:68. or elec-

18. Takakusaki K, Habaguchi T, Ohtinata-Sugimoto J, Saitoh
K, Sakamoto T. 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.
19. Takakusaki K, Habaguchi T, Saitoh K, Kohyama J.
Chang- es in the excitability of hindlimb motoneurons
during muscular atonia induced by stimulating the
pedunculopontine tegmental nucleus in cats.
Neuroscience 2004;124: 467-480.
20. Takakusaki K, Obara K, Nozu T, Okumura T.
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.
21. Sherman D, Fuller PM, Marcus J, Yu J, Zhang P,
Cham- berlin NL, et al. Anatomical location of the
mesencephalic locomotor region and its possible role in
locomotion, posture, cataplexy, and parkinsonism.
Front Neurol 2015;6: 140.
22. Kuze B, Matsuyama K, Matsui T, Miyata H, Mori S.
Seg- ment-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. Matsuyama K, Takakusaki K, Nakajima K, Mori S.
Multi- segmental innervation of single pontine
reticulospinal axons in the cervico-thoracic region of
the cat: anterograde PHA-L tracing study. J Comp Neurol
1997;377:234-250.
24. Matsuyama K, Drew T. Vestibulospinal and reticulospinal
neuronal activity during locomotion in the intact cat. I.
Walking on a level surface. J Neurophysiol
2000;84:2237- 2256.
25. 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.
26. Rossignol S. Neural control of stereotypic limb move-
ments. In: Rowell LB, Sheperd JT, editors. Handbook
of physiology, section 12. Exercise: regulation and
integration of multiple systems. New York, NY: Oxford
Universi- ty Press, 1996;173-216.
27. Mori S, Matsui T, Kuze B, Asanome M, Nakajima K,
Mat- suyama K. Cerebellar-induced locomotion:
reticulospinal control of spinal rhythm generating
mechanism in cats. Ann N Y Acad Sci 1998;860:94-105.
28. Fung SJ, Barnes CD. Evidence of facilitatory
coerulospinal action in lumbar motoneurons of cats.
Brain Res 1981;216: 299-311.
29. Mori S, Kawahara K, Sakamoto T, Aoki M, Tomiyama
T. Setting and resetting of level of postural muscle
tone in decerebrate cat by stimulation of brain stem. J
Neuro- physiol 1982;48:737-748.
30. Sakai M, Matsunaga M, Kubota A, Yamanishi Y,
Nishiza- wa Y. Reduction in excessive muscle tone by
selective de- pletion of serotonin in intercollicularly
decerebrated rats. Brain Res 2000;860:104-111.
31. Takakusaki K, Saitoh K, Harada H, Okumura T,
Sakamoto
T. Evidence for a role of basal ganglia in the regulation of
rapid eye movement sleep by electrical and chemical
stimulation for the pedunculopontine tegmental
nucleus and the substantia nigra pars reticulata in
decerebrate cats. Neuroscience 2004;124:207-220.
32. Sławińska U, Kasicki S. Theta-like rhythm in depth
EEG activity of hypothalamic areas during spontaneous
www.e-jmd.org
JM
J Mov Disord 2017;10(1):1-
trically induced locomotion in the rat. Brain Res 1995;678: 117-126.
33. Swanson LW, Mogenson GJ. Neural mechanisms for the functional coupling of
autonomic, endocrine and somato- motor responses in adaptive behavior. Brain Res
1981;228: 1-34.
34. Lynd-Balta E, Haber SN. Primate striatonigral projections: a comparison of the
sensorimotor-related striatum and the ventral striatum. J Comp Neurol
1994;345:562-578.
35. Robertson B, Kardamakis A, Capantini L, Pérez-Fernán- dez J, Suryanarayana SM,
Wallén P, et al. The lamprey blue- print of the mammalian nervous system. Prog
Brain Res 2014;212:337-349.
36. Rossignol S, Dubuc R, Gossard JP. Dynamic sensorimotor interactions in locomotion.
Physiol Rev 2006;86:89-154.
37. Rossignol S, Barrière G, Frigon A, Barthélemy D, Bouyer L, Provencher J, et al.
Plasticity of locomotor sensorimotor interactions after peripheral and/or spinal
lesions. Brain Res Rev 2008;57:228-240.
38. McCrea DA, Rybak IA. Organization of mammalian locomotor rhythm and pattern
generation. Brain Res Rev 2008; 57:134-46.
39. Jankowska E. Interneuronal relay in spinal pathways from proprioceptors. Prog
Neurobiol 1992;38:335-378.
40. Matsuyama K, Takakusaki K. Organizing principles of ax- onal 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. New York, NY: Nova Science Publishing, 2009:335-356.
41. Pearson KG. Generating the walking gait: role of sensory feedback. Prog Brain Res
2004;143:123-129.
42. Frigon A, Sirois J, Gossard JP. Effects of ankle and hip muscle afferent inputs on
rhythm generation during fic- tive locomotion. J Neurophysiol 2010;103:1591-1605.
43. Forssberg H. Stumbling corrective reaction: a phase-dependent compensatory
reaction during locomotion. J Neu- rophysiol 1979;42:936-953.
44. Bjursten LM, Norrsell K, Norrsell U. Behavioural reperto- ry of cats without cerebral
cortex from infancy. Exp Brain Res 1976;25:115-130.
45. Adkins RJ, Cegnar MR, Rafuse DD. Differential effects of lesions of the anterior and
posterior sigmoid gyri in cats. Brain Res 1971;30:411-414.
46. Villablanca JR. Why do we have a caudate nucleus? Acta Neurobiol Exp (Wars)
2010;70:95-105.
47. Denny-Brown D. The midbrain and motor integration. Proc R Soc Med
1962;55:527-538.
48. Villablanca J, Marcus R. Sleep-wakefulness, EEG and behavioral studies of chronic
cats without neocortex and striatum: the ‘diencephalic’ cat. Arch Ital Biol
1972;110:348- 382.
49. Eidelberg E, Yu J. Effects of corticospinal lesions upon treadmill locomotion by
cats. Exp Brain Res 1981;43:101- 103.
50. Liddell EGT, Phillips CG. Pyramidal section in the cat. Brain 1944;67:1-9.
51. Brooks VB, Stoney SD Jr. Motor mechanisms: the role of the pyramidal system in
motor control. Annu Rev Physiol 1971;33:337-392.
52. Vicario 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.
53. Maurer C, Mergner T, Peterka RJ. Multisensory control of
2
Posture-Gait
Control
human upright stance. Exp Brain Res 2006;171:231-250. step initiation in older adults. J Gerontol A Biol Sci Med Sci 2011;66:
54. Mergner T, Becker W. A modeling approach to the
human spatial orientation system. Ann N Y Acad Sci
2003;1004: 303-315.
55. Horak FB, Shupert CL, Dietz V, Horstmann G. Vestibular
and somatosensory contributions to responses to head
and body displacements in stance. Exp Brain Res
1994; 100:93-106.
56. Shaikh AG, Meng H, Angelaki DE. Multiple reference
frames for motion in the primate cerebellum. J
Neurosci 2004;24:4491-4497.
57. Kravitz DJ, Saleem KS, Baker CI, Mishkin M. A new
neural framework for visuospatial processing. Nat
Rev Neu- rosci 2011;12:217-230.
58. Georgopoulos AP, Grillner S. Visuomotor coordination in
reaching and locomotion. Science 1989;245:1209-1210.
59. Lajoie K, Andujar JE, Pearson K, Drew T. Neurons in
area 5 of the posterior parietal cortex in the cat
contribute to in- terlimb coordination during visually
guided locomotion: a role in working memory. J
Neurophysiol 2010;103:2234- 2254.
60. Marigold DS, Drew T. Contribution of cells in the
posteri- or parietal cortex to the planning of visually
guided locomotion in the cat: effects of temporary
visual interruption. J Neurophysiol 2011;105:2457-2470.
61. Massion J. Movement, posture and equilibrium:
interac- tion and coordination. Prog Neurobiol
1992;38:35-56.
62. Nakajima K, Mori F, Tachibana A, Nambu A, Mori S.
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.
63. Mori F, Nakajima K, Tachibana A, Nambu A, Mori S.
Cortical mechanisms for the control of bipedal
locomotion in Japanese monkeys: II. Local inactivation
of the supplementary motor area (SMA). Neurosci Res
2003;46(Sup- pl 1):S157.
64. 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.
65. Keizer K, Kuypers HG. Distribution of corticospinal
neurons with collaterals to the lower brain stem
reticular formation in monkey (Macaca fascicularis).
Exp Brain Res 1989; 74:311-318.
66. Aravamuthan BR, McNab JA, Miller KL, Rushworth
M, Jenkinson N, Stein JF, et al. Cortical and subcortical
connections within the pedunculopontine nucleus of
the primate Macaca mulatta determined using
probabilistic diffusion tractography. J Clin Neurosci
2009;16:413-420.
67. Jacobs JV, Lou JS, Kraakevik JA, Horak FB. The supple-
mentary motor area contributes to the timing of the
anticipatory postural adjustment during step initiation
in par- ticipants with and without Parkinson’s disease.
Neuroscience 2009;164:877-885.
68. Hoshi E, Tanji J. Distinctions between dorsal and
ventral premotor areas: anatomical connectivity and
functional properties. Curr Opin Neurobiol 2007;17:234-
242.
69. Snijders AH, van de Warrenburg BP, Giladi N, Bloem
BR. Neurological gait disorders in elderly people:
clinical approach and classification. Lancet Neurol
2007;6:63-74.
70. Cohen RG, Nutt JG, Horak FB. Errors in postural
preparation lead to increased choice reaction times for
www.e-jmd.org
JM
J Mov Disord 2017;10(1):1-
705-713. 81. Guldin WO, Grüsser OJ. Is there a vestibular cortex?
71. Barbieri G, Gissot AS, Fouque Trends Neurosci 1998;21:254-259.
F, Casillas JM, Pozzo T, Péren- 82. Brandt T, Dieterich M. The vestibular cortex. Its locations,
nou D. Does proprioception functions, and disorders. Ann N Y Acad Sci
contribute to the sense of 1999;871:293- 312.
verticality? Exp Brain Res 83. Sugiuchi Y, Izawa Y, Ebata S, Shinoda Y. Vestibular
2008;185:545-552. cortical area in the periarcuate cortex: its afferent and
72. Bisdorff AR, Wolsley CJ, efferent projections. Ann N Y Acad Sci 2005;1039:111-
Anastasopoulos D, 123.
Bronstein AM, Gresty MA. 84. Barra J, Marquer A, Joassin R, Reymond C, Metge L,
The perception of body Chauvineau V, et al. Humans use internal models to
verticality (subjective construct and update a sense of verticality. Brain
postural vertical) in peripheral 2010;133(Pt 12):3552-3563.
and central vestibular 85. Maffei V, Mazzarella E, Piras F, Spalletta G, Caltagirone C,
disorders. Brain 1996;119(Pt Lacquaniti F, et al. Processing of visual gravitational
5):1523-1534. motion in the peri-sylvian cortex: evidence from
73. Merfeld DM, Zupan L, brain-damaged patients. Cortex 2016;78:55-69.
Peterka RJ. Humans use 86. Zhang LL, Wang JQ, Qi RR, Pan LL, Li M, Cai YL.
internal models to estimate Motion sickness: current knowledge and recent advance.
gravity and linear CNS Neu- rosci Ther 2016;22:15-24.
acceleration. Nature 87. Pérennou D, Piscicelli C, Barbieri G, Jaeger M, Marquer
1999;398:615-618. A, Barra J. Measuring verticality perception after stroke:
74. Van Beuzekom AD, Van why and how? Neurophysiol Clin 2014;44:25-32.
Gisbergen JA. Properties of 88. Karnath HO, Dieterich M. Spatial neglect--a vestibular
the internal representation of disorder? Brain 2006;129(Pt 2):293-305.
gravity inferred from spatial- 89. Wilson VJ, Zarzecki P, Schor RH, Isu N, Rose PK, Sato
di- rection and body-tilt H, et al. Cortical influences on the vestibular nuclei of
estimates. J Neurophysiol the cat. Exp Brain Res 1999;125:1-13.
2000;84: 11-27. 90. Akbarian S, Grüsser OJ, Guldin WO. Corticofugal
75. Pérennou DA, Mazibrada G, connections between the cerebral cortex and
Chauvineau V, Greenwood brainstem vestibular nuclei in the macaque monkey. J
R, Rothwell J, Gresty MA, Comp Neurol 1994;339:421-437.
et al. Lateropulsion, pushing
and verticality perception in
hemisphere stroke: a causal
relationship? Brain
2008;131(Pt 9):2401-2413.
76. Lopez C, Falconer CJ,
Deroualle D, Mast FW. In the
presence of others: self-
location, balance control and
vestibular processing.
Neurophysiol Clin
2015;45:241-254.
77. 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.
78. Lopez C, Blanke O. The
thalamocortical vestibular
system in animals and
humans. Brain Res Rev
2011;67:119-146.
79. Fukushima K.
Corticovestibular
interactions: anatomy,
electrophysiology, and
functional considerations. Exp
Brain Res 1997;117:1-16.
80. Faugier-Grimaud S, Ventre J.
Anatomic connections of in-
ferior parietal cortex (area 7)
with subcortical structures
related to vestibulo-ocular
function in a monkey
(Macaca fascicularis). J Comp
Neurol 1989;280:1-14.
2
Posture-Gait
Control
91. Akbarian S, Grüsser OJ, Guldin WO. Corticofugal 110. Brown LL, Schneider JS,
projections to the vestibular nuclei in squirrel Lidsky TI. Sensory and
monkeys: further evidence of multiple cortical cognitive
vestibular fields. J Comp Neurol 1993;332:89-104.
92. Ticini LF, Klose U, Nägele T, Karnath HO. Perfusion
imaging in pusher syndrome to investigate the neural
substrates involved in controlling upright body position.
PLoS One 2009;4:e5737.
93. 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.
94. Büttner U, Glasauer S, Glonti L, Guan Y, Kipiani E,
Kleine J, et al. Multimodal signal integration in
vestibular neurons of the primate fastigial nucleus.
Ann N Y Acad Sci 2003;1004:241-251.
95. McCall AA, Miller DJ, Catanzaro MF, Cotter LA, Yates
BJ. Hindlimb movement modulates the activity of rostral
fastigial nucleus neurons that process vestibular
input. Exp Brain Res 2015;233:2411-2419.
96. Cavdar S, Onat FY, Yananli HR, Sehirli US, Tulay C,
Saka E, et al. Cerebellar connections to the rostral
reticular nucleus of the thalamus in the rat. J Anat
2002;201:485-491.
97. 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.
98. Llinas R. Mechanisms of supraspinal actions upon
spinal cord activities. Differences between reticular and
cerebellar inhibitory actions upon alpha extensor
motoneurons. J Neurophysiol 1964;27:1117-1126.
99. Eccles JC, Nicoll RA, Schwarz WF, Táboriková H,
Willey TJ. Reticulospinal neurons with and without
monosynap- tic inputs from cerebellar nuclei. J
Neurophysiol 1975;38: 513-530.
100. Fukushima K, Peterson BW, Uchino Y, Coulter JD,
Wilson VJ. Direct fastigiospinal fibers in the cat. Brain
Res 1977; 126:538-542.
101. Bostan AC, Dum RP, Strick PL. Cerebellar networks
with the cerebral cortex and basal ganglia. Trends Cogn
Sci 2013; 17:241-254.
102. Sasaki K, Kawaguchi S, Oka H, Sakai M, Mizuno N.
Elec- trophysiological studies on the cerebellocerebral
projections in monkeys. Exp Brain Res 1976;24:495-
507.
103. Amino Y, Kyuhou S, Matsuzaki R, Gemba H. Cerebello-
thalamo-cortical projections to the posterior parietal
cortex in the macaque monkey. Neurosci Lett
2001;309:29- 32.
104. 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.
105. Middleton FA, Strick PL. Basal ganglia and cerebellar
loops: motor and cognitive circuits. Brain Res Rev
2000;31: 236-250.
106. Hikosaka O. GABAergic output of the basal ganglia. Prog
Brain Res 2007;160:209-226.
107. Tarnutzer AA, Marti S, Straumann D. Gravity
perception in cerebellar patients. Prog Brain Res
2008;171:369-372.
108. Timmann D, Horak FB. Perturbed step initiation in
cerebellar subjects: 2. Modification of anticipatory
postural adjustments. Exp Brain Res 2001;141:110-120.
109. Bostan AC, Dum RP, Strick PL. The basal ganglia
com- municate with the cerebellum. Proc Natl Acad
Sci U S A 2010;107:8452-8456.
www.e-jmd.org
JM
J Mov Disord 2017;10(1):1-
functions of the basal ganglia. Curr Opin Neurobiol 1997; 7:157-163.
111. Bloem BR, Valkenburg VV, Slabbekoorn M, van Dijk JG. The multiple tasks test.
Strategies in Parkinson’s disease. Exp Brain Res 2001;137:478-486.
112. Bhatia KP, Marsden CD. The behavioural and motor conse- quences of focal lesions
of the basal ganglia in man. Brain 1994;117(Pt 4):859-876.
113. Takakusaki K, Saitoh K, Harada H, Kashiwayanagi M. Role of basal ganglia-
brainstem pathways in the control of motor behaviors. Neurosci Res 2004;50:137-151.
114. Filion M, Tremblay L. Abnormal spontaneous activity of globus pallidus neurons in
monkeys with MPTP-induced parkinsonism. Brain Res 1991;547:142-151.
115. Nambu A. Seven problems on the basal ganglia. Curr Opin Neurobiol 2008;18:595-
604.
116. Bohnen NI, Albin RL. The cholinergic system and Parkin- son disease. Behav Brain
Res 2011;221:564-573.
117. Hirsch EC, Graybiel AM, Duyckaerts C, Javoy-Agid F. Neuronal loss in the
pedunculopontine tegmental nucleus in Parkinson disease and in progressive
supranuclear palsy. Proc Natl Acad Sci U S A 1987;84:5976-5980.
118. Jellinger K. The pedunculopontine nucleus in Parkinson’s disease, progressive
supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry
1988;51:540-543.
119. Zweig RM, Jankel WR, Hedreen JC, Mayeux R, Price DL. The pedunculopontine
nucleus in Parkinson’s disease. Ann Neurol 1989;26:41-46.
120. Müller ML, Albin RL, Kotagal V, Koeppe RA, Scott PJ, Frey KA, et al. Thalamic
cholinergic innervation and postural sensory integration function in Parkinson’s
disease. Brain. 2013;136(Pt 11):3282-3289.
121. Jones BE. From waking to sleeping: neuronal and chemical substrates. Trends
Pharmacol Sci 2005;26:578-586.
122. Steriade M, McCormick DA, Sejnowski TJ. Thalamocorti- cal oscillations in the
sleeping and aroused brain. Science 1993;262:679-685.
123. Winn P. Experimental studies of pedunculopontine functions: are they motor,
sensory or integrative? Parkinson- ism Relat Disord 2008;14 Suppl 2:S194-S198.
124. Dautan D, Huerta-Ocampo I, Witten IB, Deisseroth K, Bolam JP, Gerdjikov T, 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.
125. Mena-Segovia J, Winn P, Bolam JP. Cholinergic modula- tion of midbrain
dopaminergic systems. Brain Res Rev 2008;58:265-271.
126. Takakusaki K, Shiroyama T, Yamamoto T, Kitai ST. Cho- linergic and noncholinergic
tegmental pedunculopontine projection neurons in rats revealed by intracellular
label- ing. J Comp Neurol 1996;371:345-361.
127. Hasselmo ME, Sarter M. Modes and models of forebrain cholinergic
neuromodulation of cognition. Neuropsycho- pharmacology 2011;36:52-73.
128. Hanakawa T, Fukuyama H, Katsumi Y, Honda M, Shiba- saki H. Enhanced lateral
premotor activity during paradoxical gait in Parkinson’s disease. Ann Neurol
1999;45: 329-336.
129. Hanakawa T, Katsumi Y, Fukuyama H, Honda M, Hayashi T, Kimura J, et al.
Mechanisms underlying gait disturbance in Parkinson’s disease: a single photon
emission computed tomography study. Brain 1999;122(Pt 7):1271- 1282.
130. Bohnen NI, Müller ML, Koeppe RA, Studenski SA, Kil- bourn MA, Frey KA, et
al. History of falls in Parkinson
2
Posture-Gait
Control
disease is associated with reduced cholinergic activity.

gneuret E, et al. Gait is associated with an increase in
Neurology 2009;73:1670-1676.
tonic firing of the sub-cuneiform nucleus neurons.
131. Müller ML, Bohnen NI. Cholinergic dysfunction in
Neurosci- ence 2009;158:1201-1205.
Par- kinson’s disease. Curr Neurol Neurosci Rep
150. Thevathasan W, Pogosyan A, Hyam JA, Jenkinson N,
2013;13:377.
Foltynie T, Limousin P, et al. Alpha oscillations in the
132. Scocco DH, Wagner JN, Racosta J, Chade A,
pedunculopontine nucleus correlate with gait
Gershanik OS. Subjective visual vertical in Pisa
performance in parkinsonism. Brain 2012;135(Pt 1):148-
syndrome. Parkin- sonism Relat Disord 2014;20:878-883.
160.
133. Vitale C, Marcelli V, Furia T, Santangelo G, Cozzolino
151. Benarroch EE. Pedunculopontine nucleus: functional
A, Longo K, et al. Vestibular impairment and adaptive
organization and clinical implications. Neurology
postural imbalance in parkinsonian patients with
2013;80: 1148-1155.
lateral trunk flexion. Mov Disord 2011;26:1458-1463.
152. Hamani C, Moro E, Lozano AM. The pedunculopontine
134. Villarejo A, Camacho A, García-Ramos R, Moreno T, Pe-
nucleus as a target for deep brain stimulation. J Neural
nas M, Juntas R, et al. Cholinergic-dopaminergic
Transm (Vienna) 2011;118:1461-1468.
imbalance in Pisa syndrome. Clin Neuropharmacol
153. Pereira EA, Nandi D, Jenkinson N, Stein JF, Green
2003;26: 119-121.
AL, Aziz TZ. Pedunculopontine stimulation from
135. Doherty KM, van de Warrenburg BP, Peralta MC,
primate to patient. J Neural Transm (Vienna)
Silveira- Moriyama L, Azulay JP, Gershanik OS, et al.
2011;118:1453-1460.
Postural de- formities in Parkinson’s disease. Lancet
154. Stefani A, Lozano AM, Peppe A, Stanzione P, Galati
Neurol 2011;10: 538-549.
S, Tropepi D, et al. Bilateral deep brain stimulation of
136. Vaugoyeau M, Azulay JP. Role of sensory information
the pedunculopontine and subthalamic nuclei in severe
in the control of postural orientation in Parkinson’s
Parkin- son’s disease. Brain 2007;130:1596-1607.
disease. J Neurol Sci 2010;289:66-68.
155. Mazzone P, Sposato S, Insola A, Scarnati E. The clinical
137. Vaugoyeau M, Viel S, Assaiante C, Amblard B, Azulay
effects of deep brain stimulation of the
JP. Impaired vertical postural control and
pedunculopontine tegmental nucleus in movement
proprioceptive integration deficits in Parkinson’s
disorders may not be related to the anatomical target,
disease. Neuroscience 2007;146:852-863.
leads location, and setup of electrical stimulation.
138. Pollak L, Prohorov T, Kushnir M, Rabey M.
Neurosurgery 2013;73:894-906; dis- cussion 905-906.
Vestibulocer- vical reflexes in idiopathic Parkinson
156. Ferraye MU, Debû B, Fraix V, Goetz L, Ardouin C,
disease. Neurophysi- ol Clin 2009;39:235-240.
Yelnik J, et al. Effects of pedunculopontine nucleus area
139. Michel SF, Arias Carrión O, Correa TE, Alejandro PL,
stimulation on gait disorders in Parkinson’s disease.
Micheli F. Pisa syndrome. Clin Neuropharmacol
Brain 2010; 133(Pt 1):205-214.
2015;38: 135-140.
157. Moro E, Hamani C, Poon YY, Al-Khairallah T,
140. Solla P, Cannas A, Congia S, Floris G, Aste R, Tacconi P,
Dostrovsky JO, Hutchison WD, et al. Unilateral
et al. Levodopa/carbidopa/entacapone-induced acute
pedunculopontine stimulation improves falls in
Pisa syndrome in a Parkinson’s disease patient. J
Parkinson’s disease. Brain 2010;133(Pt 1):215-224.
Neurol Sci 2008;275:154-156.
158. Mazzone P, Scarnati E, Garcia-Rill E. Commentary:
141. van de Warrenburg BP, Bhatia KP, Quinn NP. Pisa
the pedunculopontine nucleus: clinical experience, basic
syndrome after unilateral pallidotomy in Parkinson’s
questions and future directions. J Neural Transm (Vienna)
disease: an unrecognised, delayed adverse event? J
2011;118: 1391-1396.
Neurol Neuro- surg Psychiatry 2007;78:329-330.
159. Mazzone P, Vilela Filho O, Viselli F, Insola A, Sposato
142. Spanaki C, Zafeiris S, Plaitakis A. Levodopa-
S, Vitale F, et al. Our first decade of experience in deep
aggravated lateral flexion of the neck and trunk as a
brain stimulation of the brainstem: elucidating the
delayed phenomenon of unilateral pallidotomy. Mov
mechanism of action of stimulation of the ventrolateral
Disord 2010;25:655- 656.
pontine tegmentum. J Neural Transm (Vienna)
143. Mirdamadi JL. Cerebellar role in Parkinson’s disease.
2016;123:751-767.
J Neurophysiol 2016;116:917-919.
160. Alam M, Schwabe K, Krauss JK. The
144. Lewis MM, Galley S, Johnson S, Stevenson J, Huang
pedunculopontine nucleus area: critical evaluation of
X, McKeown MJ. The role of the cerebellum in the
interspecies differences relevant for its use as a target
pathophysiology of Parkinson’s disease. Can J Neurol Sci
for deep brain stimulation. Brain 2011;134(Pt 1):11-23.
2013;40: 299-306.
161. Karachi C, André A, Bertasi E, Bardinet E, Lehéricy
145. Roseberry TK, Lee AM, Lalive AL, Wilbrecht L, Bonci
S, Bernard FA. Functional parcellation of the lateral
A, Kreitzer AC. Cell-type-specific control of brainstem
mesen- cephalus. J Neurosci 2012;32:9396-9401.
locomotor circuits by basal ganglia. Cell 2016;164:526-
162. Fling BW, Cohen RG, Mancini M, Carpenter SD, Fair
537.
DA, Nutt JG, et al. Functional reorganization of the
146. Castrioto A, Piscicelli C, Perennou D, Krack P, Debu
locomotor network in Parkinson patients with freezing
B. The pathogenesis of Pisa syndrome in Parkinson’s
of gait. PLoS One 2014;9:e100291.
disease. Mov Disord 2014;29:1100-1117.
163. Schweder PM, Hansen PC, Green AL, Quaghebeur G,
147. Karachi C, Grabli D, Bernard FA, Tandé D, Wattiez N,
Stein J, Aziz TZ. Connectivity of the
Be- laid H, et al. Cholinergic mesencephalic neurons
pedunculopontine nucleus in parkinsonian freezing of
are involved in gait and postural disorders in Parkinson
gait. Neuroreport 2010; 21:914-916.
disease. J Clin Invest 2010;120:2745-2754.
164. Snijders AH, Takakusaki K, Debu B, Lozano AM,
148. Rinne JO, Ma SY, Lee MS, Collan Y, Röyttä M. Loss of
Krishna V, Fasano A, et al. Physiology of freezing of gait.
cholinergic neurons in the pedunculopontine nucleus
Ann Neu- rol 2016;80:644-659.
in Parkinson’s disease is related to disability of the
165. Takakusaki K, Takahashi M, Obara K, Chiba R.
patients. Parkinsonism Relat Disord 2008;14:553-557.
Neural substrates involved in the control of posture.
149. Piallat B, Chabardès S, Torres N, Fraix V, Goetz L, Sei-
Adv Robot 2016 Dec 6 [Epub].
http://dx.doi.org/10.1080/01691864.201 6.1252690.
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https://doi.org/10.14802/jmd.16062 / J Mov Disord 2017;10(1):1-17 pISSN

for Posture and

Attri- bution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0)

Copyright © 2017 The Korean Movement Disorder Society 1

GENERAL SCHEMA OF emotional, goal-directed behaviors are always

BRAINSTEM AND SPINAL

Copyright © 2017 The Korean Movement Disorder Society 3

Role of the mesencephalic area in the

characterized by extension of the unilateral limb

A Stimulation sites B Stimulation effects

Locomotor pathway and its control by

A Location of medullary reticulospinal neurons B Changes in postural muscle tone

a. Suppression-relatedb. Hypertonus-relatedc. Locomotion-modulated

tegmental area, hippocampus and amygdala. On

Excitatory system Inhibitory system Locomotor pathway

Spinal locomotor network

Inhibitory interneuronsMotoneurons Excitatory system

Spinal locomotor network

Organization of the spinal locomotor network

Spinal control of muscle tone

the limbic-hypothalamic structures, and the

are at higher risk of falling particularly when patho- physiological

Action on the brainstem structures

Cerebellar actions on the cerebral cortex

Posture-gait control by the basal ganglia

and vestibular graviception,133 may result in deficits to the decrease in

Failure in motor programming

Reduced activity in posture-gait area in the midbrain

posture deficiency in PD, deep brain Acknowledgments

Circuits 2015;9:68. or elec-

disease is associated with reduced cholinergic activity.

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