A consideration of sensory factors involved in motor functions of the basal ganglia

Brain Research Reviews, 9 (1985) 133-146

133

Elsevier BRR 90024

A Consideration

of Sensory Factors Involved in Motor Functions of the Basal Ganglia T. I. LIDSKY’, C. MANETTOi and J. S. SCHNEIDER2

‘Division of Veterinary Biology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute, Blacksburg, VA 24061 and 2Department of Psychiatry, University of California Medical School, Los Angeles, CA 90024 (U.S.A.)

(Accepted December llth, 1984) Key words: basal ganglia-movement

- sensorimotor - sensory gating

CONTENTS Introduction

.............................................................................................................................................

133

Basal ganglia and movement: traditional analyses .............................................................................................. 2.1. Lesions ............................................................................................................................................. 2.2. Stimulation ........................................................................................................................................ 2.3. Unit activity during movement ................................................................................................................ 2.4. Discussion .........................................................................................................................................

134 134 135 135 135

Sensory processing in the BG ........................................................................................................................ 3.1. Acute experiments ............................................................................................................................... 3.2. Chronic experiments ............................................................................................................................ 3.3. Discussion .........................................................................................................................................

137 137 137 137

BG effects on sensory processing.. ................................................................................................................... 4.1. Significance for motor control ................................................................................................................. 4.2. Possible pathways of BG gating ............................................................................................................... 4.3. Discussion .........................................................................................................................................

138 138 139 140

Conclusions ..............................................................................................................................................

143

Summary .....................................................................................................................................................

143

Acknowledgements References

........................................................................................................................................

...................................................................................................................................................

1. INTRODUCTION

Suggestions that the basal ganglia (BG)* are involved in the control of movement date back at least 300 year+. With DeLong’s pioneering chronic unit studies in the 1970’s (ref. 16, 18), there was great promise that some of the mysteries of this system’s

144 144

motor functioning would be unraveled. However, despite a burgeoning of research interest in the BG, this early promise has not been fulfilled. Using a combination of advanced neurophysiological techniques (e.g. single cell recording, microstimulation, etc.) great progress has been made in the study and analysis of neural structures involved in

Correspondence: T. I. Lidsky, Division of Veterinary Biology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute, Blacksburg, VA 24061, U.S.A. * Throughout the past years, there have been many brain areas that at one time or another have been included under the rubric of ‘basal ganglia’. Presently, and for the purpose of this paper, BG structures are taken to include the caudate nucleus (CN) and putamen (PU), (collectively referred to as the striatum), the globus pallidus (GP) and the substantia nigra (SN).

134 movement. Inherent to the research design that has evolved for this use has been a focus on movement as the endpoint

in the analysis of a motor system. That

is, the effects of any experimental

manipulation

sought in terms of their consequences parameters

of the muscle response

graphy of movement. sociate9,

are

on either the or on the topo-

The work of Evarts and his as-

where they show precise correlations

tween the firing patterns of pyramidal and the characteristics of movements,

be-

tract neurons illustrates the

point, the results obtained

from the use of the stand-

ard motor systems approach with the BG will be compared with the data obtained with its use on other motor areas. As an example of the latter, motor cortex is used. The data are categorized (lesion,

stimulation,

unit recording).

by methodology Where

possi-

ble, data from a variety of species are cited. When commonality

of results are observed across species, it

is parsimonious to assume that a basic property of the BG is being tapped.

efficacy of this research protocol. Because of its suggested role in movement,

this re-

search design has been used extensively in work on the BG. However, the results obtained with BG use have been largely equivocal in nature. The shortcomings of the application of the traditional motor systems approach to the BG serve as the point of departure for the present paper. This review has been designed with 4 general aims in mind. First, a brief synopsis of the large literature concerning traditional motor analyses of the BG is presented. Second, some of the reasons why this approach may be inappropriate as the sole paradigm for BG research are discussed. Third, an additional approach for investigating the BG is described. Fourth, results from research employing this latter approach are summarized and the model of BG functioning that emerges from these data is discussed. 2. BASAL GANGLIA

AND MOVEMENT:

TRADITION-

AL ANALYSES

The following is an overview of the enormous literature that has emerged from traditional analyses of BG functioning, This is not intended as a thorough review because a summary such as this is neither the aim nor within the scope of the present paper*. Rather, the present synopsis is intended to illustrate the rather surprising limitations of the traditional motor systems approach when it has been applied to BG research. Although, initially, considerable knowledge was gained concerning the motor functions of the RG, the overall success of this paradigm has been relatively limited when compared with the outcome of its use with other motor systems. To underscore this

Lesions in motor cortex result in clear cut motor deficits. Typically, immediate paralysis of the muscles subserved by the damaged area resultss’. Although over time considerable recovery of function is observed, long-lasting defects persist in fine motor control. In contrast, severe motor dysfunction resulting from experimentally induced BG damage has been infrequently observed**. Liles found that smalf lesions in the head of the CN of cats resulted in increased frequency of species typical movement patterns (e.g. treading)dY. Large lesions in the striatum of monkeys resulted in myocionus and catotonia, however, these lesions often included extrastriatal tissueI”. In rats, striatal lesions produced slight hypotonia and weakness of the contralateral forelimb2’. GP lesions produced similar effects and, in addition to these, a disruption of eating and drinking@. There has been some suggestion that oral movement problems underlie these ingestional difficulties. It should be noted that the movement problems associated with GP lesions are, at best, very subtle and have not been detected by all investigators4”. Perhaps the most intriguing results concerning BG damage have been reported by Vihablanca and his colleagues in an extensive series of papers. They made very large aspiration lesions of the CN (70-10096 damage) with remarkably little extra-caudate encroachment. ‘The neurological examinations revealed surprisingly few . , _motor deficits in chronic bilaterally acaudate cats’. ‘In brief, after l-2 months little or no abnormalities were detectable . except for a subjective lack of ‘elegance’. ‘slowness’ and ‘impoverishment’ in the everyday mo-

* For a more thorough coverage of the BG literature, the reader is referred to several excelfent reviewsi’Jg’.‘j? ** The results of clinical studies of BG disease are difficult to interpret. The associated neuropathology is typically diffuse and rarely or never confined to the BG.

135 tor activities

. . .‘. ‘Even complex

motor

perform-

flect the topography

The rela-

ance such as catching a mouse, adopting defensive postures, jumping up and down, etc., appeared to be normal’s”. The lack of gross motor deficits is partic-

tionship

ularly significant

stance, there have been reports that striatal and GP

since the CN comprises

the bulk of

between

of the movement*i.

the striatum in the cat. In the monkey, such a result could be explained on the basis of the different corti-

neurons

cal connections

activations.

for the CN as compared

That is, motor cortex projects PU in primates

to the PUi7.

preferentially

to the

so that CN lesions might not be ex-

pected to result in gross motor deficits. In the cat, on the other hand, there is a dense projection from precruciate motor areas to the CNz4. 2.2. Stimulation Contractions of only one or perhaps a few muscles at short fixed latencies are obtained with low intensity electrical stimulation of motor cortex6. Early studies of the effects of BG stimulation also reported evoked movement. Subsequent work, however, suggests that these results were largely due to current spread to adjacent areasdi. Although occasional reports of motor activity caused by BG stimulation do appear in the literature56, re-assessment of these findings shows the current spread hypothesis to be valid47.85. Thus, in contrast to studies of motor cortex, low level stimulation of the BG does not evoke localized motor activity. Stimulation of theBG, although ineffective in eliciting movements directly, does modulate motor responses evoked by stimulation in other areas. For example, movements evoked by stimulation of motor cortexsO. amygdalasi, reticular formation34 and peripheral nervessiJ6 , can either be attenuated or facilitated by prior BG stimulation. With respect to modulation of movements evoked from other motor areas, the BG resemble nuclei not traditionally thought of as having a pure motor role. Similar effects have been reported for electrical stimulation of the amygdala*s, hippocampus’s and lateral hypothalamu@. The BG, like many ‘non-motor’ areas elicit contraversive locomotion when stimulateds. 2.3. Unit activity during movement Activity in motor cortex shows precise relationships to movement, that is, the neurons change firing rate before the onset of EMG activity and, more importantly, show patterns of activity that closely re-

BG unit activity and movement

is

less clearly defined and has been a subject of debate concerning the details of this relationship. For inchange firing rate well before the onset of muscle activity17J9, or only after the onset of EMG Others have found that during a succes-

sion of individual

movements

trial to trial variation

there is considerable

in unit response

in a series of movements,

latency.

Thus,

the same cell can fire be-

fore, during, or after the onset of EMG activation33.64. Compared to the activity of other motor areas, BG neurons’ firing encodes relatively few parameters of movement. Striatal activity reflects movement direction, dynamic and static load. In the case of the latter, the authors noted that the effects ‘were relatively weak++. GP neurons also encode movement direction. In addition, GP unit firing reflects amplitude and/or velocity of movement26. It should be noted that the encoding of load by the striatum and amplitude/velocity by the GP appears to be relatively coarsegrained when compared to the response properties of other motor areas. Specifically, there is considerable variation, as reflected in large standard deviations, in the mean responses at each level of a given movement parameter in the published data (cf. ref. 14, Fig. 12 and ref. 26, Fig. 5). 2.4. Discussion There are several general conclusions that may be drawn from the experiments described in the preceding review. The absence of stimulation-evoked muscle activity suggests that the BG have an indirect role in movement. The temporal relationship between BG activation and muscle response is inconsistent with a major influence in movement initiation. The rather coarse grained encoding of a limited number of motor components does not suggest BG mediated control of the parameters of movement particularly because these same parameters are much more precisely encoded by neurons in other motor areas. Taken together, the preceding suggests more about what the BG do not do rather than the reverse. Surprisingly little can be deduced from these findings concerning the nature of the BG’s role in movement, and in particular, the actual mechanisms by which

136 BG influences question

are brought

to bear.

The following

must then be asked: why has the research

cortex and the reticulospinal tracts, collectively, it is tenuous to suggest that these indirect pathways af-

approach that was so successful with other motor sys-

ford the BG motor influence.

tems not proven

mary motor

wholly satisfactory

Part of the answer

with the BG?

comes from a consideration

of

functions

Few would impute pri-

to prefrontal

cortex

on the

weight of its output to STN or to the lateral hypothal-

some of the details of the BG’s anatomy.

amus which projects to NTPP.

The best understood motor areas share one anatomical feature; relatively direct access to the effec-

The major point to be gleaned from the preceding anatomical description is that the BG are quite far re-

tors. Thus, the ventral

jects to muscles via the axons of alpha- and fusimo-

moved (in terms of numbers of synapses) from the final common path. This anatomical fact suggests plau-

torneurons.

sible reasons for the failure of the standard

Motor

bers to the ventral

horn of the spinal cord pro-

cortex sends pyramidal

tract fi-

horn and the cerebellum

affects

tems

approach

in investigating

motor sys-

the BG’s

role

in

both motor cortex via thalamocortical projections and also the spinal cord via rubrospinal, vestibulospinal and reticulospinal tracts. In contrast, the BG are relatively far removed from the final common path. The targets of BG output that are most closely associated with motor function are thalamic nuclei ventralis lateralis, and ventralis anterio+. The major portion of these nuclei that receive BG afferents projects to premotor cortex and the supplementary motor area72.77 (termed motor association area@). It is unclear, however, whether or not the neurons receiving BG influences are interneurons or thalamocortical projection cell+. In the context of access to the final common path, it is significant that the ultimate destination of BG influences are motor association areas rather than primary motor cortex. These cortical areas, untike primary motor cortex, are not tightly coupled to movement. The projections of premotor and supplementary motor cortices into the spinal cord are sparse. In addition, electrical stimulation of motor association areas does not evoke contractions in individual muscles and unit activity in these regions does not encode many of the parameters of ongoing movements-i. Additional routes the BG have to the final common path are through indirect connections with structures involved in motor control. Both the GP

movement. A strict focus on movement as the independent variable is appropriate only for the analysis of neural systems with relatively direct access to lower motorneurons because close functional proximity to the final common path is indicative of an involvement in the control of the parameters of movement (e.g., velocity and force). Thus, manipulation of these systems causes subsequent events that are observable in the activity of the muscles themselves. On the other hand, areas that are more distant from motoneurons are more involved in the complex antecedents of movement (e.g. learning, attention and memory). To elucidate the functioning of such a system (consider. for example, a motor association area such as parietal cortex). the research approach must allow for more than just the observation of muscle activity. What then is an appropriate strategy to be used in BG research? Descriptions of the sequelae of BG damage suggest that sensory factors in movement as well as movement per se must be assessed to more fully appreciate the functioning of this system. Martin53 observed that. with many BG diseases, patients had most difficulties with movements that were triggered or strongly controlled by sensory stimuli (particularly somatosensory and vestibular). However, movements involving the same muscles could be

and the SN project to the nucleus tegmenti pedunculopontinus (NTPP)i7.**,5*. Additionally, the GP is the major source of inputs to the subthalamic nucleus (STN). NTPP sends axons to nucleus reticularis gigantocellularis which in turn gives rise to reticulospi-

made in essentially normal fashion in situations where sensory involvement was minimal. In view of the diffuse brain damage that accompanies BG diseases in humans, it is precarious to base conclusions on the study of symptomatologyl7. However, similar sensory-based motor deficits have recently been described in experimental animals with highly restricted BG damagesi.“).

nal fibers while STN has direct projections to both premotor and motor cortex. Although the ultimate destinations of these BG projections are to structures involved in motor control, premotor cortex, motor

137 influences

3. SENSORY PROCESSING IN THE BG

from zones that are relevant

dance of tongue, 3.1. Acute experiments comparatively few researchers Until recently, have focused on the sensory aspects of BG func-

examined.

tioning.

a variety of lesion, stimulation

The earliest

demonstrations

that BG neu-

rons respond to sensory stimulation were made in acutely prepared, anesthetized cat&‘o. The most extensive investigations

of these effects have been car-

ried out by Krauthamer and his associates past two decades37Js. They demonstrated

over the that the

BG respond to somatosensory, auditory, and visual inputs with many neurons showing multimodal convergence. Moreover, neurons that were affected by two or more sensory modalities responded with qualitatively similar reactions to the different inputs. In terms of percentage of cells affected, though, they found that somatosensory inputs were most effective, followed by auditory, and then visual inputs, respectively. These findings are complimented by clinical reports: in humans with BG damage, somatosensory controlled movements are more disturbed while visually guided movements remain comparatively intactss. In acute studies, it has been typically observed that the responses of BG units to stimuli of different modalities are qualitatively similar. As a result, BG sensory responses appeared to be non-specific. Based on this, Krauthamer has suggested that the BG’s role in movement involves arousal37.38. However, this suggestion was guarded in view of the intrusive effects of anesthetics and paralytic drugs. 3.2. Chronic experiments To circumvent the possible confounds inherent in acute neurophysiology, the analysis of sensory processing in the BG was extended to awake, restrained animaW$67. Attention was focused on somatosensory influences in view of the prepotency of this modality as described in the experimental and clinical literature. To allow increased depth of analysis, only those somatosensory influences that were associated with categories of movements that are clearly under BG control were examined. Although BG damage disrupts the activities of virtually all muscle groups, tongue, mouth and head movements are often among the most severely affectedi9,4”. Consequently, the mechanisms by which the BG process somatosensory

These

areas innervated

for the gui-

mouth and head movements zones are the perioral by the trigeminal

were

and facial

nerve.

It should be noted that previous observations gations

from

and single unit investi-

show that the relationship

between

the BG

and movements of the tongue, mouth and head does not differ significantly from BG relationships with movements

of other muscle systems39.40.43.44. There-

fore, examinations relevant

of BG trigeminal

to understanding

interactions

the more general

are

role of

the BG in motor control. It was found, as in acute work, that BG neurons responded to sensory stimulation6s.67. However, while sensory responses in anesthetized cats were non-specific, responses in awake animals showed the encoding of information that appeared to be relevant for motor control. As a stimulus approached the mouth, progressively more cells would fire, while those already active would respond with increasing vigor. Conversely, as the stimulus moved away from the mouth, the number of cells firing would decrease, and those still active would show successively weaker responses. Moreover, because of the directional sensitivity of some striatal cells, a tactile stimulus moving toward the mouth at any point would evoke more activity than would stimulation at that same point moving away from the mouth. Taken together, these response properties suggest the encoding of stimulus movement and location. Rather than this function being performed in an absolute sense, the location and movement of a stimulus seemed to be noted with respect to the mouth (‘orocentric’). 3.3. Discussion Thus, many BG neurons have distinct sensory properties. Moreover, the information abstracted from a sensory event by the BG differs markedly from the information extracted by the primary sensory pathways (e.g. the lemniscal system). In the lemniscal system, for example, the salient features abstracted from a cutaneous event include a precise estimation of magnitude, absolute location and absolute direction of movements7. In contrast, the BG more or less ignore stimulus magnitude, and encode the direction and location of stimulus movement rela-

138 tive to the mouth. What is the functional of the kind of sensory information

significance

used to influence

that the BG proc-

ess? Consideration of the information necessary for somesthetically controlled movements (e.g. head movements

made

by a cat attempting

mouse) is useful in attempting

to bite

a

to answer this ques-

Benita

the arm’s movement.

et al.8 trained

cats to perform

a ballistic

movement of the forelimb upon presentation of an auditory signal. Cooling the CN caused a cessation in the performance movement.

of this sensory-triggered

forelimb

This deficit was not due to a simple dis-

tion. As the cat moves its head to bring the prey ob-

turbance

ject to the front of the mouth, it is not as important know that the movement causes the prey object

could make ‘quick and accurate’ forelimb movements despite caudate cooling. Other observations

to to

brush the first and then the second vibrissa in the dorsal portion of the field (lemniscal information) as it would be to know that the movement causes the prey object to move away from the mouth (BG information). In order for the information abstracted by the lemniscal system to become action-oriented, it must go through intermediary stages of translation from a form that is appropriate for sensory discrimination, to a form primarily useful for motor control. Apparently, this translation takes place in the BG. In effect, the BG function as a sensory analyzer for motor systems. Clinical studies are in accord with the idea developed in the preceding paragraph. Humans with BG disease* have problems when movements must be made under somatosensory control. ‘. . . precision of movements performed under visual control is little if at all affected in Parkinsonian subjects, while, in the absence of vision, errors of position are markedly worsened, indicating an increased dependence on visual information to control movement in these subjects’m. Further support for this idea comes from 3 recent experiments. Hore et al.31 trained monkeys to position a lever under either visual or proprioceptive guidance. Cryogenic inactivation of the GP severely disrupted the proprioceptively guided movements. However, these same animals were able to continue to accurately position the lever using visual feedback. This study indicates the critical importance of the somatosensory modality for BG functioning. Moreover, the relatively unimpaired movements made with visual assistance demonstrate that normal BG functioning is not critical for programming of the arm movement per se. Rather, the integrity of the BG is necessary when the somatosensory modality is

of motor control:

in other contexts

animals

suggested that the performance deficit did not stem from attentional or motivational disturbances. Analogous results were found with GP lesions in ratsdo.@. Head, trunk and limb movements of braindamaged rats were abnormat when these activities had to be made on the basis of restricted somatosensory information. These abnormalities were not due to general motor loss however. Movements that were not highly dependent on somatosensory feedback were not affected. In many respects. the behavior of rats with GP damage resembled that of animals with peripheral sensory nerve lesions (H.P. Zeigler, personal communication). Since neurological examination of rats with GP lesions revealed no sensory loss per se, these animals’ similarity to animals with peripheral nerve cuts became apparent only when movements had to be generated on the basis of somatosensory feedback. In effect, these animal’s movements seemed deprived of somatosensory guidance. 4. BG EFFECTS

ON SENSORY

PROCESSING

Significance for motor control A critical question that comes to mind at this point is: if the BG function as a sensory analyzer for motor systems, how does the BG’s processing of sensory information ultimately affect movement? Several studies involving the effects of BG stimulation on other brain areas are a logical source for a possible answer. It has been repeatedly demonstrated that the BG influence somatosensory. auditory and visual processing37JXJ’j. For example, stimulation of the BG inhibits auditory and visual cortical evoked potentials37,i8. Lemniscal and extralemniscal components of the somatosensory system are also modified by the BG. For example, the sensory responsiveness of second 4.1.

* The usual discfaimer should be noted with respect to these clinical observations. BG disease in humans is usually associated with diffuse brain damage. However, it is plausible that the sensory-related motor problems are caused by BG damage in view of the similar difficulties of experimental animals with more restricted damage.

139 order neurons

in the trigeminal

is altered by activation Similarly,

BG

stimulation

processing in neurons specific’ thalamus37Js,

main sensory nucleus

of either the CN or the GP39. affects

somatosensory

in the hypothalamusls, ‘noncerebellum”* and in neurons

stimulus

evoked predation.

Animals

with damage

in

these areas failed to respond to perioral sensory stimuli, which, in the intact cat, evoked positioning ments and the jaw opening

component

move-

of biting. No

motor loss per se was detected in lesioned animals’.

It should be noted that,

In other work it was shown that small GP lesions

unlike movements that have been evoked by BG stimuIation, modulatory influences on sensory proc-

increased the excitability of trigeminal motoneurons. This increase in excitability was not due to re-

essing are probably not due to the spread of current to structures adjacent to the BG. In general, the cur-

moval of BG mediated

of the reticular

formation39.

rent levels necessary

to affect sensory responses

are

lower than those needed to evoke movement. Moreover, several studies that reported modulation of sensory processing by BG stimulation carefully controlled for the possibility of artifactual current spreadsJ9Js. Thus, BG activity can exert powerful modulating effects on the processing of sensory information in other parts of the brain. But, what is the potential significance of these sensory effects for the control of movement? Can influences on sensory processing have relatively direct consequences for movement? Studies of feline predation suggest that the answer to the latter question is affirmative. Under certain conditions, sensory processing is altered by the brain so that normally ineffective stimuli will trigger complex movement patterns that form components of prey catching behavior*z. Thus, control of sensory processing can be an effective means of motor control. As the BG have demonstrably strong influences on sensory processing, it is plausible to suggest that these influences are part of the mechanism by which the BG affect movement. Several studies support this hypothesis . The nucleus accumbens, based on cytology, neuroanatomy and pharmacology, is considered by some to be part of the BG*s. Stimulation of this area inhibits predatory attack in cats. The apparent basis of this effect is a reduction in the size of the sensitized zone on the upper lip which, when brushed, triggered components of biting seen during predation. These data led Goldstein and Siegel to suggest that ‘other stimulus and goal directed behaviors (e.g. feeding and mating) may also be understood in terms of response components made operative by the emergence of receptive fields’z’. Other work has shown that damage in the nigrostriatal and/or striatonigral tracts also interferes with

chronic inhibition

of the tri-

geminal system. Rather, BG damage allowed excitatory sensory inputs, which are normally gated out, to have access to the trigeminal

motor nucleus66.

Changes in sensory-evoked motor responses with BG manipulations are not solely observed in the context of electrically evoked behaviors. Unilateral injection of muscimol (a GABA agonist) into the SN of rats induces an asymmetry in responsiveness to tactile stimulation of the face, ‘. . . touching or pricking of the contralateral lip, cheek, or vibrissae elicited a behavior sequence consisting of withdrawal of the lip, followed frequently by a sudden rapid movement of the mouth toward the probe and a vigorous biting or mouthing of the probe’. These sensory-evoked responses could only be elicited from the side opposite the muscimol injection. Similar movements could not be evoked in non-drugged animal+. 4.2. Possible pathways of BG gating These data indicate that the BG can affect movement by gating sensory inputs into motor systems. Anatomical and electrophysiological evidence suggests that this effect can potentially be exerted at many levels of the neuraxis. The 3 most likely candidates are discussed below: (a) thalamic nuciei ventralis lateralis and ventralis anterior; (b) thalamic nuclei centromedianum and parafascicularis; and (c) the brainstem. It should be noted that these alternatives are not mutually exclusive. (a) A major BG output terminates in thalamic nuclei ventralis anterior and ventralis lateralis*s5ss. Little is known of these areas with regard to sensory gating. The major output targets of these nuclei are two cortical zones: premotor cortex and the supplementary motor area (SMA)*sJs. Recent stimulation and chronic unit studies of SMA have led Tanji and Taniguchi to suggest that this cortical area ‘plays a part in modifying the input-output relation in motor cortex in a behavioral context where usage of the

140 sensory input is essential

for proficient

performances

of a motor task’rs. Such a function is, in effect, sensory gating. In view of the large BG projection to ventralis anterior

and ventralis

lateralis and the output of

these thalamic nuclei to premotor

cortex and SMA, it

is reasonable to assume that the activities of these cortical zones are determined, in part, by the BG. The similarities

of the results from two chronic unit

of all neural tissue rostra1 to the thalamus

and hypo-

thalamus indicating that the nigral influence exerted at diencephalic and/or more caudal level+.

is

Two areas that may critically figure in the BG’s descending influence are the medial and lateral parabrachial nuclei. Recent findings show that these regions are directly affected by the BG6s. Moreover, the parabrachial nuclei project to several motor

studies, one of the SMA, and the other of the BG,

areas; the hypoglossal

support this. Thirty one percent of SMA units fired only during sensory-triggered movements. More-

nal cord and the cerebellar vermis6s771.75. The latter might be particularly important in the context of the

over, these responses

BG’s role in sensory

were modality-specific:

units

with responses accompanying movements triggered by one modality stimulus (e.g. somatosensory) did not fire during similar movements elicited by stimuli of other modalities (e.g. auditory, visual)74. Similar to cells sampled in the SMA, many BG units fired only in association with sensory-evoked movements rather than all movements. However, these unit responses were not sensory responses: on trials in which the stimulus evoked no movement, unit firing rate did not change. In addition, unit firing changes were temporally associated with the onset of movement rather then presentation of the stimulus. As in the SMA, BG movement responses were stimulusspecific. Units with potent activity changes accompanying movements evoked by one stimulus showed no response with movements of similar topography evoked by a different stimulussl. (b) A major BG output synapses in centre medianum and parafascicularis

of the thalamus2sFss. Kraut-

hamer and his associates, along with other laboratories, have documented extensively the polysensory responsivity of neurons in these thalamic nuclei37Js. Centre medianum and parafascicularis project heavily upon premotor cortical areas. Therefore, these nuclei are in an ideal position to supply sensory information to cortical areas with motor influence. BG stimulation evokes EPSP-IPSP sequences in these thalamic multimodal neurons. By virtue of this influence, then the BG can regulate the sensory information that reaches cortical motor zones. (c) Several reports suggest the possibility of BG mediated sensory gating at various brainstem levels. As stated earlier, injection of GABA agonists into the SN of rats sensitized biting reflexes that were elicited by touching the perioral region. This drug-induced sensitization persists unaltered after removal

and trigeminal

gating.

Crispino

nuclei, the spi-

and Bullock

have shown that the stimulation of the vermis alters multimodal sensory processing at both midbrain and cortical levelsi3. BG stimulation, possibly via parabrachial relays, alters both spontaneous unit activity and sensory processing in the vermisds. Anterior hypothalamic neurons receive convergent auditory, visual and somatosensory inputs. Lesions in the BG result in a decrease of convergence and an overall decrease in sensory responsiveness of hypothalamic neuron@. In the context of the suggestions made in this paper concerning possible mechanisms of BG involvement in motor control, it is important to note the suggested role of the hypothalamus in visceromotor processes and oro-ingestive motor patterns. As previously mentioned, small GP lesions increase the excitability of trigeminal motorneurons by allowing sensory afferents an increased ease of access to the motor nuclei. The fact that large cortical or thalamic lesions made in concert with GP damage do not eliminate the increased trigeminal excitability, indicates that BG influences are exerted, in part, at levels caudal to the thalamus66. 4.3. Discussion These data indicate that the BG have the potential to affect movement by gating sensory inputs into other motor systems that have more direct access to the final common path. It follows, then, that the BG’s involvement in a given movement would vary with the role played by sensory stimulation in that movement. Thus, BG motor functioning could come into play in the initiation, guidance or even termination of a movement insofar as these various epochs entail sensory input (particularly somatosensory input). Similarly, the motor consequences of BG damage would

141 vary with the sensory context of muscle activity rath-

stimuli which, in intact individuals,

er than the particular

postural

the movement.

muscle group or the metrics of

Several

concrete

examples

are con-

sidered in the following paragraphs. In a study by Anderson et al.“, units were recorded in the BG of awake monkeys performing a task in which visual and somatic stimuli signalled the need for wrist movements. A large population of BG cells were activated during the behavior. However, many cells that fired in relation to movement did so only when the movement was triggered by a specific sensory event.

‘This result would not be expected

in a

activities.

able to make

However,

voluntary

invariably

these

movements

same muscles in other context@.

evoked

patients

were

involving

Again,

the

caution

is

needed in interpreting these findings because of the diffuse nature of brain damage in people with BG disorders. The BG’s ability to translate

receptor-referenced

sensory input into motor-relevant information suggests an involvement in more than movement initiation. Motor activities that are subject to modification by sensory

feedback

would,

presumably,

entail BG

cell having a simple relationship to wrist movement and indicates that neurons in the movement-related category must be specified by the additional variable, the type of sensory input’. Analogous results have been observed in the CN of moving catssr. Cells fired preferentially during movements that had strong sensory involvement rather than all movements. CN unit responsiveness could not be predicted on the basis of any of the parameters associated with the movement. The only requirement for CN unit responsiveness was a movement evoked by a specific sensory stimulus. Frequently, movement sequences are triggered by a sensory event. For activities such as these, BG functioning would be critical for movement initiation. Conversely, BG dysfunction would result in either increased response latency or complete failure to move. Normal and GP lesioned rats were tested for the ability to track and lick a moving spoutm. The start of a tracking trial was signalled by the somatosensory stimulation caused by the spout brushing the

participation throughout. Movements that are preprogrammed on the basis of sensory information would only require BG functioning during early stages. However, for both types of movement, a major result of BG dysfunction would be inaccuracy. Olmstead and Villablanca61 assessed the ability of intact and acaudate cats to extend the forepaws through a narrow opening to retrieve chunks of meat. Brain damaged animals showed severe deficits: movements were ‘quite inaccurate, often many centimeters from the meat’. Similar types of deficits affect sensory controlled bar press behavior42369 and head orientation@ in rats with GP lesions. After inactivation of the GP by cooling, monkeys are no longer able to accurately position a lever using proprioceptive feedbacksi. Patients with Parkinson’s disease are unable to insert a bite plate into their mouths and keep it there. Their major difficulty stems from an inability to bring the head into a position that would allow the mouth to surround the bite plate. These types of head movements are made on the basis of perioral

face. Brain damaged rats were unable to track the spout in spite of their ability to make appropriately directed head movements. Apparently a major cause of the GP lesioned rats’ difficulties was that movements were initiated ‘too late’ after spout displacement. Similarly, disruptive electrical stimulation of the CN in cats impaired visually cued forelimb movements. In well-trained animals, the disruptive effect of stimulation was not due to induced visual perceptual difficulties. Rather, reaction time was increased: . . the animal performs smoothly and rapidly when he makes his response, but shows difficulty in initiating it’lo. Analogous problems have been described in humans with BG pathology. These patients failed to make postural movements in response to sensory

feedback. It should be noted that these patients’ difficulties are not due to a simple motor impairment involving the neck, since movements involving nuchal musculature can be made in other contexts (C. Markum, personal communication). The preceding examples indicate that the BG would be involved in the initiation, guidance or even termination of a movement insofar as these various motor epochs entailed sensory input. Since the importance of afference in a motor activity depends upon many factors (e.g. context, experience), specific parameters such as speed, direction or force cannot a priori be attributed to BG functioning. Thus, in contrast to Kornhuber’s implication of the BG acting exclusively in ramp movementse, the present paper

142 suggests involvement in certain ballistic actions as well as ramp movements. Empirical studies support this suggestion

since cooling of the BG disrupts both

types of movementsJ2. The answers

to questions

seemingly anomalous

raised by a number

or contradictory

of

findings in BG

research appear to be found in the sensory-based model of BG functioning. There has been a continuous debate

concerning

that

movement-related

show

movement,

for example,

the percentage activity.

the reported

of BG cells With

arm

percentages

evokes contraversive

circling at variable

1atencies”i.

However, with respect to these final two results, BG stimulation produces effects that are similar or identical to those produced by stimulation of structures not traditionally thought to have primary motor functions (e.g. amygdala, hippocampus and lateral hypothalamus22~55~7s). The reason for this difference between the BG and other motor systems with respect to low-intensity

electrical

stimulation

is clear.

The

BG influence movements by gating sensory inputs into other motor systems. In the absence of an appro-

range from 1% (ref. 76) to as much as 37% (ref. 16).

priate sensory event, electrical stimulation

These discrepant reports are reconcilable because the involvement of sensory stimuli in movements as well as the particular type of sensory stimuli used in eliciting the movement vary from study to study. Recently, CN unit responsiveness was observed during head movements of similar topography made either on the basis of somatosensory control or in the absence of a distinctive sensory stimulus. It was found that 80% of the CN units fired during the former

would not be expected to produce movement. Recent findings from other laboratories, that are difficult to reconcile with traditional models of BG functioning, fit well with the notions described in this paper. Following caudatectomy, male cats display ‘estrus-like’ behavior that consists of lordosis, tail deviation away from the side stimulated. rear limbs treading and, occasionally. vocalization. Analysis of plasma testosterone and 17 beta-estradiol failed to reveal a hormonal basis for these post-lesion behavioral change+. Based upon this hormonal analysis

while only 10% fired during the lattersi. In other work DeLongi8 demonstrated, in support of Kornhuber’s theory, that putamen units fire preferentially in relation to ramp rather than ballistic movements. In apparent contradiction, Benita et al.8 found that cooling the GP impaired ballistic movements. These results could be predicted on the basis of the ideas set out in this paper. The role of sensory inputs was quite different in the ballistic movements studied by DeLong as compared to the ballistic movements studied by Benita et al. In the former case, ballistic movements were self-generated so that the role of afference was minimal. In the latter case, the ballistic movements were studied in a reaction time paradigm: movements were triggered by sensory stimuli. The ideas developed in this paper also explain why the effects of electrical stimulation of the BG differ from the effects of stimulating other motor systems. Low-intensity electrical stimulation of a variety of motor structures evokes movement at short fixed latencies”. In contrast, low level stimulation of the BG produces no motor activity”‘.“7.8”. At much higher stimulation levels, unilateral BG stimulation can modulate motor activity evoked by stimulation delivered to other motor structures (e.g. motor cortex)“(J.6().In addition, high intensity BG stimulation

of the BG

and results from their previous studie@iJo, the authors ‘concluded that the striking changes in lordotic behavior seen in the cats with extensive caudate lesions are most probably due to the increased somatosensory reactivity seen in these animals .‘Q. There is extensive evidence that implicates the BG in attentional processesirJ’, a function not commonly associated with motor systems operations. These problematic attentional functions would also be predictable on the basis of the ideas described here. Problems in attention are inferred from a lack of motor response to sensory stimuli. After BG lesions, sensory stimuli would not be translated into a form relevant for motor control and, appropriate afferences would not be gated into motor systems. Novel stimuli would consequently be incapable of evoking adequate behavioral responses. Psychiatric disturbance is often a concomitant of BG disease in humans35,“6. Why cognitive and emotional symptoms result from damage to a motor systern is an intriguing question. Psychiatric symptoms do not result from the handicaps imposed by BG movement problems since the onset of psychiatric disturbance frequently precedes the appearance of motor

symptoms.

The sensory

based

motor

func-

143 tioning of the BG described

in this paper makes the

monic role in movement30.

However,

variety of empirical

findings described

sible. Subtle sensory disturbances in normal individuals can result in ideation qualitatively similar to that of psychiatrically disturbed patient@. It is not im-

based

would

plausible to assume that the sensory-motor abnormalities associated with BG dysfunction could also pro-

SUMMARY

presence

of psychiatric

symptoms

more comprehen-

duce cognitive disturbances. Several lines of evidence suggest that a disturbance of dopaminergic activity underlies many forms of psychosisss.46. The highest concentrations mine, by several orders of magnitude,

of dopa-

reside in the

BG. Because of this, some investigators have suggested that psychosis is caused by BG dysfunctionss.46. The ideas developed in the present paper marshal1 support of an entirely different nature for BG involvement in psychosis. A large body of literature suggests that a ‘defect in sensory gating’i may cause many of the symptoms of schizophrenia. Such a functional defect would be expected to result from a BG disturbance. 5. CONCLUSIONS

The premise of this paper is that insights into the BG’s role in motor processes can be gained by consideration of sensory aspects of this neural system’s functioning. Two major points were made in this context. First, the BG function as a sensory analyzer for motor systems. Afferent information is translated by the BG into a form which is directly relevant for motor control. Second, the BG exert influences upon movement by regulating the ease with which sensory afference gains access to motorneurons. A particular strength of this conceptualization is that it has explanatory power that reconciles some of the more puzzling contradictions in the BG literature. In addition, it brings some of the diverse behavioral functions (e.g. attention) in which the BG has been implicated back under the rubric of this system’s motor functioning. The ideas outlined in the preceding paragraphs are not intended as a comprehensive theory of BG functioning. Many symptoms common to different BG pathologies (e.g. tremor at rest) are not easily explicable in terms of the concepts developed in this paper. Moreover, recent studies of SN neural activity, while providing evidence for sensory-based functioning, additionally suggest that the BG have a mne-

functioning

component

represent

here, sensoryone significant

in the BG’s motor involvement.

There is a sizeable literature glia (BG) functioning periments ditionally

based upon the

concerning

basal gan-

that is based on data from ex-

employing a method of analysis that is traused with other motor areas. A brief re-

view of this literature is presented and the following conclusion is reached: as compared to the success of traditional methodologies in elucidating the workings of other motor systems, their use in BG investigations has proven disappointing. A possible reason for the shortcomings of traditional analyses in BG research is discussed. The remainder of this review concerns an alternative approach to the study of the BG that follows from consideration of a variety of clinical and experimental findings. The literature suggests that sensory aspects of BG functioning must be taken into account to fully appreciate the role of this system in motor control. A review of the literature concerning the latter suggests two points: 1. The BG function as sensory analyzer for motor systems. That is, the BG convert sensory data from a form that is receptor oriented to a form that is relevant for guiding movement. 2. The BG ultimately affect movement by gating sensory inputs into other motor areas rather than by directly affecting these areas. This sensory-based model of BG functioning explains a number of apparent discrepancies in the literature. In addition, seemingly anomalous findings are reconciled with the overwhelming evidence that the BG are a motor system. In particular, the suggestions of a BG role in attention and cognition are viewed as being intrinsic rather than orthogonal to the role of the BG in movement. ACKNOWLEDGEMENTS

We wish to acknowledge the helpful comments of Drs. C. H. Markum, M. S. Levine and J. S. Schwartzbaum. In addition, we wish to thank Linda Lewis, Barbara Jones and Patrick Elliott for help in preparation of this manuscript. Supported by NINCDS grant no. NS 21418.

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