Role of Basal Ganglia Balance Control · 2020. 1. 14. · 2001d; Bhatia&Marsden, 1994). Majorfunctions of the basal ganglia and examples of the consequences of basal ganglia dysfunction

NEURAL PLASTICITY VOLUME 12, NO. 2-3, 2005

Role of the Basal Ganglia in Balance Control

Jasper E. Visser and Bastiaan R. Bloem

Department ofNeurology, University Medical Center St Radboud, Nijmegen, the Netherlands

SUMMARY

In this review paper, we summarize theimportant contributions of the basal ganglia tothe regulation of postural control. After a briefoverview of basal ganglia circuitries, theemphasis is on clinical observations in patientswith focal lesions in parts of the basal ganglia,as the impairments seen here can serve tohighlight the normal functions of the basalganglia nuclei in postural control. Two par-ticularly relevant functions are discussed indetail: first, the contribution of the basal gangliato flexibility and to gaining control of balance-correcting responses, including the ability tolend priority to the elements of a postural task;and second, processing afferent information bythe basal ganglia, which is increasingly recog-nized as being highly relevant for posturalcontrol.

1. INTRODUCTION

The term basal ganglia refers to a group ofsubcortical nuclei that includes the striatum, globuspallidus, and connected structures. The striatum isdivided into a dorsal division that includes thecaudate and putamen, and a ventral division that

Reprint requests to: Jasper E. Visser, MD, UniversityMedical Center St Radboud, Department of Neurology(326), P.O. Box 9101, 6500 HB Nijmegen, theNetherlands; Email: [email protected]

includes the amygdala and olfactory tubercle. Thesubthalamic nucleus and the substantia nigra (SN)are often considered together with the basal gangliabecause of their important reciprocal connections.

Functionally, the basal ganglia have long beenregarded to be predominantly involved in motorcontrol but are now increasingly recognized to playan additional role in sensory processing, cognition,and behavior (Brown et al., 1997; Bloem et al.,2001 d; Bhatia & Marsden, 1994). Major functionsof the basal ganglia and examples of theconsequences of basal ganglia dysfunction forpostural control are shown in Table 1.

Here we will focus on the important andversatile role of the basal ganglia in controllingbalance. Our aim is to provide an overview of therole of the basal ganglia in balance control byreviewing observations on postural control inpatients with basal ganglia lesions. The firstsection will briefly describe the neuroanatomy andneurochemistry of basal ganglia circuits and theirconnections. In particular, the basal gangliaconnections with brainstem nuclei will be discussedas these are increasingly recognized as contributingto postural control.

Next, the role of several basal ganglia nuclei inpostural control will be illustrated by clinicalobservations on patients with focal basal ganglialesions as this underscores the balance-relatedfunctions of the basal ganglia.

Finally, we will discuss several aspects ofbalance control in which the basal ganglia might beinvolved, including motor programming, muscletone control, and sensory-motor integration.Indirectly, the observations on elderly patients can

(C) 2005 Freund Publishing House Ltd. 161

.162 J.E. VISSER AND B.R. BLOEM

TABLE 1

Functions ofthe basal ganglia that might be relevant for postural control

Basal ganglia functionExample

(dysfunction seen in patients with basal ganglia disease)

Storing and automatic execution of motor plans

Motor flexibility, adaptive behavior toenvironmental changes

Somatosensory integration

Muscle tone regulation

Gain control of automatic postural responses

Cognition, motivation and emotional aspects ofbehavior

Gait akinesia freezing

Postural "inflexibility"

Stooped posture

Contraversive pushing

Axial stiffness

Exaggerated destabilizing responses

Diminished stabilizing responses

Co-contracti on

Impaired scaling of postural responses underconditions of uncertainty

Fear of falling

shed some light on the developmental aspects ofthe basal ganglia and balance, a field that hasotherwise received little scientific attention.Indeed, brain lesions in patients with degenerativediseases can provide insight into the possible roleof the basal ganglia in the pathophysiology ofdevelopmental disorders.

2. ORGANIZATION OF THE BASAL GANGLIAAND PATHWAYS

The neural connections within the basal gangliaand their projections are complicated (Parent &Hazrati, 1995a; Hamani et al., 2004; Pahapill &Lozano, 2000). Several simplified models havebeen proposed. The traditional model recognizesseveral parallel loops through the basal ganglia(Alexander & Crutcher, 1990). These loops share a

common neuroanatomical plan, but each serves

specific motor, cognitive, or behavioral functionsin a more or less segregated manner. Althoughthese models are oversimplified and not true

reflections of the actual anatomical situation(Chesselet & Delfs, 1996; Parent & Cicchetti,

1998), they do have important value as conceptualmodels for discussing the functional consequencesof localized lesions.

A schematic representation of a basal gangliacircuit and the major neurotransmitters involved is

represented in Fig. 1. Cortical input is directed to

the striatum, via glutamatergic projections (Albinet al., 1995; Parent & Hazrati, 1995b). At thestriatal level, the putamen seems mostly involved

in motor tasks, whereas cognitive and behavioralfunctions are served by the caudate nucleus and theventral striatum. The dorsal striatum projects to the

globus pallidus pars interna (GPi) and to the

BASAL GANGLIA AND BALANCE CONTROL 163

cortex

Glu

GABA

AChspinal cord

Fig. 1. Schematic model of the basal ganglia. Abbreviations" ACh, acetylcholine; DA, dopamine; GABA, gamma-hydroxy butyric acid; Glu, glutamate; GPe, globus pallidus, pars externa; GPi, globus pallidus, pars interna;PPNc, pedunculopontine nucleus, pars compacta; PPNd, pedunculopontine nucleus, pars dissipatus; SNc,substantia nigra, pars compacta; SNr, substantia nigra, pars reticulata; STN, nucleus subthalamicus. Note that theprojections of these basal ganglia circuitries are not only "ascending" to the motor cortex, but also "descending"to brainstem nuclei, the reticular formation and the spinal cord. These descending connections are increasinglyrecognized as important for various aspects of postural control.

164 J.E. VISSER AND B.R. BLOEM

pars reticulata of the substantia nigra (SNr), twoareas that share many functional and structuralproperties, often jointly regarded as the "outputnuclei" of the basal ganglia (Parent & Hazrati,1995a,b). Two separate pathways within thesestriatopallidal projections are recognized" a directpathway projecting from the striatum to theGPi/SNr, and an indirect pathway that connects thestriatum to the Gpi/SNr via the GPe and thesubthalamic nucleus (STN). Based on theexcitatory and inhibitory nature of the connections,the direct and indirect pathways through the basalganglia have opposing effects on net basal gangliaoutput. The activation of direct pathways tends todecrease inhibitory GPi/SNr output, whereas striatalexcitation increases inhibitory output via indirectpathways. Finally, the GPi/SNr connects to specificnuclei in the thalamus, and thalamic efferentsproject back to cortical areas.

In addition to the input from cortical areas, thestriatum receives dopaminergic input from the parscompacta of the substantia nigra (SNc) (Albin etal., 1995; Parent & Hazrati, 1995a,b; Alexander &Crutcher, 1990). Dopamine probably has opposingeffects on the direct and indirect pathways, suchthat the overall impact of dopamine is facilitativein nature by decreasing inhibitory basal gangliaoutput.

In addition to the thalamo-cortical projections,basal ganglia output is also directed to thebrainstem and spinal cord (Fig. 1). Specifically,GPi and SNr neurons projecting to the thalamusalso send collaterals to the pedunculopontinenucleus (PPN) and other midbrain areas, includingthe superior colliculus (Parent & Hazrati, 1995a,b).The main inputs to the PPN stem not only from theglobus pallidus and SNr but also from the STN andspinal cord (Pahapill & Lozano, 2000). Theascending PPN output connects to all parts of thebasal ganglia. The descending PPN output projectsto the medullary reticular formation, relayingbilaterally to the spinal cord. Direct projections

from the PPN to the spinal cord have also beendescribed.

The anatomical and physiological properties ofthe PPN have been reviewed recently (Pahapill &Lozano, 2000). The PNN consists of a hetero-geneous group of neurons, located in the upperbrainstem. The PPN can be regarded as part of themidbrain locomotor region (MLR), a functionallydefined area involved in controlling locomotion.Two main neuronal populations exist within thePPN: the PPN compacta (PPNc), consisting ofmainly cholinergic neurons; and the PPN dissipatus(PPNd), consisting of both cholinergic and gluta-matergic neurons. Dysfunctional projections viathe PPN may account for certain phenomena inbasal ganglia disease--including gait and balanceimpairment--that cannot be explained by traditionalbasal ganglia models (Lee et al., 2000; Pahapill &Lozano, 2000).

POSTURAL CONSEQUENCES OF BASALGANGLIA LESIONS

Why are the basal ganglia thought to contributeto balance control? One line of evidence stemsfrom clinical neurology, in which many conceptsof structure-function relationships are based onclassical lesion studies in patients and animals withfocal lesions. That is, the function of a certainstructure is suggested by the functional loss afterfocal damage to that specific structure. In thissection, we will explore the consequences of focalbrain lesions for postural control and balance.Balance impairment has frequently been observedin patients with basal ganglia lesions, e.g. inpatients with degenerative, vascular, post-infectious,toxic, neoplastic, or iatrogenic lesions of the basalganglia (Bloem & Bhatia, 2004). In this section,the reported effects of focal lesions of differentareas in the basal ganglia and several of their targetareas on balance control will be discussed.


3.1 Lesions in the basal ganglia

The best-known human example of a lesion inthe substantia nigra (SN) is Parkinson’s disease(PD), a disorder predominantly characterized bydegeneration of dopaminergic cells in the SNr(Samii et al., 2004). In PD, falling is frequent, asup to 70 percent of patients falls at least once eachyear, and some 50 percent of subjects fall twice ormore each year (Bloem et al., 2004a). The balancedisorder in PD can be regarded part of a spectrumof motor dysfunctions in axial muscles, termed"axial apraxia" (Lakke, 1985). Other examplesinclude the difficulty in turning around the verticalaxis and the characteristically stooped posture. Thepresence of these abnormalities in PD suggests aninvolvement of the SNr and its doparriinergicprojections in normal axial motor control. Notethat lesions in PD patients extend beyond the SN,certainly in more advanced disease stages. Othernon-dopaminergic areas like the locus coeruleuscan then become involved and are likely tocontribute to balance impairment (Bloem et al.,2001c).

In humans, acquired and more selective SNlesions have been studied in persons exposed to aneurotoxic heroin analogue, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), that ratherselectively destroys nigrostratiatal neurons in theSN. This destruction is associated with a markedreduction of central dopaminergic function in theputamen and caudate (Snow et al., 2000). Thesymptoms in MPTP patients are strikingly similarto those in PD patients, including gait disorders,balance impairment, and falling (Bloem & Roos,1995). The association of a selective hypodopa-minergic state with axial mobility deficits suggestsa role for the SN in at least certain elements of gaitand balance control.

Published reports on the effects of selectiveputaminal lesions on postural control are scarce.One report of nine patients with sudden falls due to

vascular basal ganglia lesions described aninvolvement of the putamen in seven subjects(Labadie et al., 1989). These patients fell "like alog", apparently not aware of the fall and hardlyusing protective movements to prevent falling. Suchobservations suggest that the putamen somehowcontributes to balance control, although the exactfunction remains unclear. As stated before, caudatelesions rarely cause motor disorders but rather areassociated with cognitive and behavioral problems,including apathy and disinhibition (Bhatia &Marsden, 1994; Alexander & Crutcher, 1990).

Important observations were made in PDpatients who had undergone stereotactic deep-brainsurgery of the basal ganglia as a treatment. Inter-ventions targeted at the GPi included stereotacticlesions or high-frequency electrical stimulationachieving the same net effect as a lesion. Unilateralinterventions can reduce contralateral symptomsand can lead to a mild, clinically noticeableimprovement of posture and gait impairment(Bakker et al., 2004). Bilateral interventions can beassociated with disabling side-effects, includingmarked postural instability. Such contrasting clinicaleffects on postural controlmbeneficial on the onehand, deleterious on the othermsuggest aninvolvement ofthe GPi in balance control.

An involvement of the STN in postural controlhas been suggested by the outcomes of PD patientssubjected to deep brain surgery. Various studiesreported improvement following bilateral STNstimulation (see e.g. Limousin et al., 1998; Deep-Brain Stimulation for Parkinson’s Disease StudyGroup, 2001; Bejjani et al., 2000; Krack et al.,2003). Adverse effects can also occur," however, aspostural instability can deteriorate in certain patients(Bakker et al., 2004). Two patients who underwenta unilateral subthalamotomy showed a markedpostoperative postural asymmetry--a lateral curva-ture of the spine with head and body tilting towardthe side contralateral to the STN lesion (Su et al.,2002). Although apparently aware of their instability,


these patients seemed to neglect their body drift.Dopaminergic medication caused partial improve-ment, but contralateral surgery corrected theabnormality. These observations underscore theinvolvement ofthe STN in balance control.

3.2 Lesions in efferent connections

Additional indirect evidence comes fromobservations on patients with balance impairmentcaused by focal lesions in areas that receiveabundant projections from the basal ganglia. Twoimportant structures include the thalamus and thePPN, both possibly serving as final pathways viawhich the basal ganglia influence balance andpostural control.

The thalamus seems involved in axial motorcontrol in multiple ways. First, the thalamus mayfunction as a relay structure for the sensory inputof different modalities to the cortex, and could assuch be involved in the graviceptive system. Forexample, patients with acute thalamic infarcts canshow a tilt of the subjective visual vertical (Karnathet al., 2000). Additional evidence suggesting aninvolvement of the thalamus in the graviceptivesystem has been suggested by observing certainstroke patients, who not only show instability dueto hemiplegia but also actively push toward thehemiplegic side. In such patients, the posterolateralthalamus is predominantly involved (Kamath et al.,2000). This involvement apparently alters theperception of the body’s orientation in relation togravity, leading to the perception of being uprightwhile the body is actually tilted. The importance ofthe thalamus for postural control is further under-scored by the effects of deep-brain surgery targetedat the thalamus. Unilateral approaches may improvepostural control, perhaps by decreasing tremor, butbilateral interventions often cause severe balanceimpairment (Speelman, 1991 ).

Degeneration of the PPN occurs in variousneurodegenerative disorders, including PD, and

can be particularly prominent in progressivesupranuclear palsy (PSP) (Bloem & Bhatia, 2004).In patients with this disorder, balance impairmentis often pronounced, and falling is even morefrequent than in PD, occurring already in earlydisease stages (Bloem et al., 2004b). The severityof balance impairment in PSP is perhaps related toa marked cell loss within the PPN (Hirsch et al.,1987). Reports on patients with selective PPNlesions are rare. One patient with a hemorrhagiclesion involving the right PPN reportedly could notstand or walk (Masdeu et al., 1994). Focal lesionsin the PPN have been performed in primates,however, in which bilateral lesions resulted inpermanent akinesia (Munro-Davies et al., 1999).Furthermore, the electrical stimulation of the PPNin macaques was associated with frequency-dependent effects. Stimulation at 100 Hz causedimpairment of postural control and rendered themonkey unable to balance itself (Nandi et al.,2002b). Furthermore, in monkeys with MPTP-parkinsonism, injection of the GABA antagonistbicuculline into the PPN resulted in significantsymptom reduction (Nandi et al., 2002a). Theresults of these animal experiments underline theimportant role of the PPN in balance control.

BASAL GANGLIA AND SPECIFIC BALANCEFUNCTIONS

We will next explore two essential functionaldomains of postural control--the regulation ofpostural flexibility and the control of sensorimotorintegration--that might be governed, at least inpart, by the basal ganglia. The emphasis will be onPD, for which most observations have been made.

4.1 Postural inflexibility

The basal ganglia are increasingly recognizedas critical structures involved in flexibility or set-


shifting, including mental flexibility as well asmotor flexibility. Being flexible is an indispensablefeature of all living organisms because flexibilityallows them to adapt to a changing environment.Balancing also requires continuous adaptation to a

rapidly changing environment, being caused eitherby externally generated perturbations, such as a

moving support surface, or by self-initiatedmovements like rising from a chair.

To cope with sudden balance perturbations,several mechanisms exist. The first are purelypassive mechanisms, such as the body’s inertia.Second, "automatic" responses are defined asbalance-correcting responses, whose onset latencyis too early for a voluntary response but strikinglyflexible in magnitude, depending on the specifictask at hand. Finally, voluntary balance correctionsare those that are purposefully initiated. Theimportance of the basal ganglia in fine-tuning allthese mechanisms has been demonstrated in post-urography experiments, the quantitative assessmentof human upright stance during quiet stance or inresponse to standardized bodily perturbations(Bloem et al., 2003).

Various investigators observed that posturalcontrol in PD is characterized by stiffening andreduced flexibility. For example, evidence hasbeen obtained for axial stiffness in PD patientswho were exposed to relatively slow platform tiltsin the sagittal plane (Maurer et al., 2003). Inaddition, PD patients who are exposed to morerapid displacements of an underlying movableplatform also show signs of stiffness at the ankles(Bloem et al., 1996) and at the pelvis and trunk(Carpenter et al., 2004). Such postural inflexibilityis associated with frequent loss of balance on theplatform, presumably because stiffness reduces thebody’s ability to dampen the impact of the externalperturbation passively, by hinging at the hips. Weshould note that stiffening in itself does notinvariably have a deleterious effect on balancecontrol because it can help to reduce the number of

degrees of freedom that have to be controlled.Several mechanisms can explain the stiffness

in PD patients. First, joint motion can be constrainedbecause of increased muscle stiffness, whichindeed occurs in ankle muscles of PD patients(Dietz et al., 1988). The muscle stiffness could becaused by secondary changes in intrinsic muscleproperties.

Second, stiffening could result from tonicincreases in background muscle activity, evenbefore postural perturbations have occurred. Suchtonically increased background activity has indeedbeen observed in PD (Schieppati & Nardone, 1991;Horak et al., 1996). These findings suggest that thebasal ganglia, in particular the SNr and its

projections to the upper dorsal brainstem, help to

optimize muscle tone for the ongoing gait orbalance task (Takakusaki et al., 2004).

Finally, stiffening could be related to animpaired scaling of automatic postural responses.We will illustrate this for a common experimentalset-up,, using toe-up rotations of a supportingplatform upon which subjects are standing. Suchperturbations move the subject backward and elicit

a monosynaptic spinal stretch response and a so-called medium latency (ML) response in thestretched triceps surae. These responses are followedby a long-latency (LL) postural response in theshortened tibialis anterior. The ML activity has a

destabilizing effect, whereas the LL responses inthe shortened antagonist help to stabilize posture.When PD patients are confronted with identicaltoe-up rotational perturbations, several differencesemerge (Allum et al., 1988; Bloem et al., 1996).First, PD patients have enlarged ML stretchresponses, and this enlargement of a destabilizingresponse is thought to induce postural instability.Second, patients have LL responses that aresmaller than normal, and a reduction of a normallystabilizing response might further lead to posturalinstability. Indeed, PD patients are more unstablethan controls on the moving platform, as reflected


by a larger posterior sway (Bloem et al., 1996).This instability suggests that PD patients have afundamental problem in sealing the magnitude oftheir postural responses. Later studies extendedthese observations by using platforms that couldsuddenly rotate or translate in multiple directions(multidirectional dynamic posturography) (Carpenteret al., 2004; Dimitrova et al., 2004). A key findingin these studies was a directional preponderancefor falls in a backward direction. This backwardfalling was again related to an abnormal scaling ofbalance correcting responses, causing co-contractionbetween agonist and antagonist muscles. Co-contraction was also a common finding in otherposturography studies of PD patients (Dietz et al.,1995; Horak et al., 1992). It remains unclear,however, whether co-contraction is purely anexpression of primary dysfunction or at least partlya compensatory strategy to cause stiffness (andfewer degrees of freedom) when other mechanismsfail.

The central nervous system can normally adaptthe postural strategies to meet the functionaldemands of the ongoing postural task (posturalset). The term postural set covers a wide array ofconditions, including changes in the environmentalsituation, changes in the subject’s initial bodyposition and changes in the subject’s perceptionsabout the postural task. Again, the basal gangliaseem to be an important mediator here, as PDpatients have particular difficulties when posturalset is manipulated.

This view can again be illustrated using thesimple toe-up rotational paradigm. Under predict-able conditions, small postural perturbations elicitcomparably small stabilizing LL responses inhealthy subjects, whereas larger perturbations elicitlarger responses (Fig. 2a, 2b). When receiving a

random mixture of small and large perturbations,young healthy subjects select a default posturalresponse that is sufficiently large to cope with thelargest possible perturbation (Beckley et al., 1991).

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B. Elderly conlrols0.6

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BI 4 degrees10 degrees

Predictable Unpredictable Predictable Unpredictable Predictable Unpredictable

Fig. 2. Response amplitude scaling of tibialis anterior LL responses for 10 young healthy subjects (A), 13 elderly healthysubjects (B) and 12 patients with PD (C). All subjects were exposed to sudden toe-up rotational movements ofsupporting forceplate, the size of which could be varied between 4 degrees or 10 degrees amplitude eitherpredictably (serial presentation of identically sized stimuli) or unpredictably (random mix of small and largeperturbations). The graphs show the grand mean and SEM for normalized LL response amplitudes for each of thetwo levels of both independent variables: forceplate amplitude (4 degrees and 10 degrees) and degree of pre-dictability ("predictable" or "unpredictable"). Data in this figure were modified from Beckley et al. (Beckley et al.,1993; Beckley et al., 1991) and reproduced from Bloem & Bhatia (2004), with permission of the authors and thepublisher.


Older subjects also select such a ’default’response, albeit one that matches the smallerperturbation size. Thus, healthy subjects canmodify the strength of their postural responsesaccording to the demands of the task at hand.Figure 2c shows that this ability is lost in PDpatients; they cannot modify the size of posturalresponses even though the magnitude of theperturbation is known in advance (Beckley et al.,1993). Furthermore, PD patients are unable toselect a default response during unpredictableconditions, leading to a fixed response size underall conditions. Similar signs of ’inflexibility’ havebeen observed under many different conditions

(Horak et al., 1992; Schieppati & Nardone, 1991;Bloem et al., 1995). The inability to modulate thesize of postural responses properly is anotherreflection of abnormal gain control by the basalganglia.

Not only shifting between different motorplans is important but also the ability to performsimultaneous tasks andmif necessary--arrangemovements according to priority. The "stopswalking when talking" test addresses this issue inthe light of balance control (Lundin-Olsson et al.,1997). In this paradigm, subjects who are unable tomaintain a routine conversation while walkinghave an increased risk of falls in the near future.Such an inability to execute two taskssimultaneously (one of them being a postural orgait task) can reflect a limited central processingcapacity of the central nervous system. Patientswith PD should be particularly vulnerable undersuch circumstances because the basal ganglia playan important role in the running of sequential orsimultaneous motor programs (Marsden, 1982).Indeed, in daily life many falls in PD patientsoccur under dual task circumstances (Willemsen etal., 2000). Surprisingly, when the "stops walkingwhen talking" is delivered test to PD patients, thiscauses no problems for most patients (Bloem et al.,2000). Under much more challenging conditions in

a truly multiple task design (Bloem et al., 2001b),however, including walking several meters andexecuting an increasing number of additionalcognitive and motor tasks at the same time, PDpatients perform poorer than do controls (Bloem etal., 2001a), as reflected by slowed or blockedperformance. Patients were less able than age-matched elderly controls to employ a "posturefirst" strategy but instead attempted to perform alltasks simultaneously. Nevertheless, because of thepatients’ balance impairment and restrictedprocessing resources neither motor nor cognitivecomponents were executed very successfully,resulting in a high proportion of errors. Thisfinding might be interpreted as a form of ’risky’behavior that might lead to falls in daily life.Apparently, the basal ganglia are also involved inregulating such priority processes, perhaps by theirability to promote a rapid switch between differenttasks.

4.2 Sensorimotor integration

The important role played by the basal gangliain integrating and weighting afferent sensory infor-mation is increasingly becoming clear. This view istrue for incoming feedback from the visual system,for the proprioceptive system, and for thevestibular system. Consequently, several motordeficits in patients with basal ganglia dysfunctionshould perhaps be viewed as--at least partiallydue to afferent disturbances.

We will briefly focus on studies that showedproprioceptive disturbances in PD. For example,the discrimination of differences in static positionsof both elbow joints is impaired in PD (Zia et al.,2000). Furthermore, PD patients cannot activelymatch, with eyes closed, the position or trajectoryof one arm to the position of the other arm, atterthis has been displaced actively by the patient(Klockgether et al., 1995; Zia et al., 2000). Otherstudies showed that PD patients find it difficult to


accurately point to remembered visual targets inthe dark, i.e. when proprioceptive informationnormally provides the most reliable source ofinformation about finger position (Adamovich etal., 2001; Keijsers et al., 2005).

Information about the position of the activelymoving arm normally originates from sensorykinesthetic feedback arising in the periphery duringthe actual movement, as well as from corollarydischarges that contain information aboutmovement plans from brain structures concernedwith movement programming and execution.Therefore, problems in PD might arise fromdefective peripheral kinesthetic feedback becausethe afferent information itself is flawed, theinformation is abnormally processed at a .centrallevel, or because patients have abnormal corollarydischarges. Studies in which arms are passivelymoved by the experimenter, therefore lackingcorollary discharges, suggest that disturbedkinesthesia, rather than incorrect efference copies,causes hypometria in PD. For example, passivearm movements seem as hypometric as self-generated movements (Klockgether et air, 1995).

Central processing abnormalities within thebasal ganglia could also affect postural control invarious ways. For example, abnormal proprioceptiveprocessing could explain the fixed gain of posturalresponses that underlies the postural inflexibility inPD. Another possibility is that patients have anabnormally constructed internal map of theirstability limits and have lost their normal sense oflimb and trunk position. Patients might also falselyperceive their subjective vertical to be shiftedbackward, forcing them to adopt a stooped posture(Kitamura et al., 1993). In addition, due to anuncertainty about actual body orientation in space,patients might assume a ’worst-case scenario’ ofconstant instability, which causes a fear of falls.Both this fear and the actual impaired afferentinput could cause stiffening, with adverse effectson dynamic postural control. In this light, it might

be possible that impaired sensory processing is atleast partly responsible for the stiffness andinflexibility as described in Sec. 4.1.

Although not exclusively seen in patients withbasal ganglia lesions, some evidence supports theconcept of incorrect self-perception resulting fromabnormal basal ganglia function. We alreadymentioned the occasional occurrence of a seeming’neglect’ for lateral instability in patients with aunilateral lesion in, for example, the putamen orthe subthalamic nucleus (Suet al., 2002; Labadieet al., 1989). In one experiment, patients wereconfronted with line drawings showing varyingdegrees of stoop and lateral deviation (Moore etal., 2000). When asked to identify the drawing thatbest resembles their self-perceived posture, patientswere likely to underestimate the severity of theirabnormalities. This finding suggests that patientshave lost their normal sense of trunk position inspace and supplements clinical experience thatmany patients are surprised to observe their ownstooped posture in a mirror. Abnormal trunkposition sense could also explain the sometimesstriking difficulties experienced by PD patients inattempting to roll over in bed (Lakke, 1985).

The pathophysiology of disturbed proprioceptionin PD remains unknown. The results of anatomicalstudies indicate that the basal ganglia receiveabundant afferent information. This renders themsuitable to serve as a ’comparator’ that reweighsthe various sensorimotor loops, matches thissensory information to the corollary dischargeinformation and translates afferent informationfrom sensory and motor sources into appropriatemotor programs. In PD patients, this afferentinformation itself is presumably normal, butproprioceptive signals are perhaps abnormallyprocessed within the basal ganglia due to defectivehigher level integration. This hypothesis is supportedby the finding of reduced sensory-evoked brainactivations in cortical and subcortical areas in PDpatients using positron emission tomography


(Boecker et al., 1999).Further supportive evidence for impaired central

proprioceptive integration in PD stems fromanimal work. For example, the pallidal neurons ofMPTP monkeys show a greatly enhanced respon-siveness to natural proprioceptive stimulation, withdecreased directional dependency (Filion et al.,1988). Hemiparkinsonian MPTP monkeys showextinction, contralateral to the lesion, whenconfronted with simultaneous bilateral stimuli(Schneider et al., 1992). Moreover, the ability touse sensory information may depend on the degreeof dopamine deficits in the SN (Jaspers et al.,1989; Martens et al., 1996). Mild deficits affectonly the ability to use static proprioceptive stimuliin motor control, whereas more pronounced deficitsalso affect the ability to overcome the proprio-ceptive deficit using visual information.

5. CONCLUSIONS

Observations on patients and animals withfocal lesions of the basal ganglia underscore thesignificance of the basal ganglia and theirprojections in regulating normal postural control.A particularly important contribution includesflexibility and the role in gain control of balance-correcting responses, which permits subjects to

change their strategy or individual posturalresponses, according to the actual needs of the taskat hand. Apart from such motor functions, the basalganglia also seem involved in the cognitive aspectsof postural control, including the handling ofuncertainty and the ability to lend priority to themost vital elements of a complex postural task. Inaddition, the involvement of the basal ganglia inprocessing afferent information is increasinglyrecognized as another important function withrelevance for postural control, possibly via theorganization of a body scheme or through onlinemodification of ballistic movements.

ACKNOWLEDGEMENTS

Jasper E. Visser and Bastiaan R. Bloem weresupported by the Prinses Beatrix Fonds.

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Role of Basal Ganglia Balance Control · 2020. 1. 14. · 2001d; Bhatia&Marsden, 1994). Majorfunctions of the basal ganglia and examples of the consequences of basal ganglia dysfunction