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Neu ro I og i ca I Control of Locomotion

IN this annotation locomotion refers basically to walking on a flat, unyielding surface. This involves the rhythmical movements of the limbs of the animal, which may be bipedal or quadripedal, although reference is made to other animals, such as the arthropods. In walking it is necessary to maintain equilibrium and counter the effects of gravity. The muscles of the limbs provide the essential propulsive force. Variations in normal walking include changes in the length of the step and its frequency, as in slow walking or running, going up or down a slope or steps, and coping with uneven ground and obstacles. It may be assumed that all these involve variations in the basic pattern of walking and its neurological control.

In this annotation developmental as- pects will not be discussed.

Spinal cord Basic concepts regarding locomotion begin with SHERRINGTON'. He showed that spinal cats and dogs developed rhythmical movements of the hind limbs

some weeks after operation, and that these movements did not depend on higher levels of the nervous system. However, he thought that the sensory input triggered a reflex contraction of the appropriate muscles which produced the stepping movements. The contracting muscles were responsible for the sensory impulses which produced the next part of the cycle. BROWN* showed that the rhythmical stepping movements could be elicited in deafferented animals and postulated that spinal cord centres controlled the muscles which contracted in an orderly sequence and produced walking movements. Nor- mally, reflexes caused by sensory input reinforced the spinal cord centres and may be necessary for adjustments to the basic rhythmical cycle.

More recently, GRILLNER and ZANG- GER3 confirmed that the regular sequence of flexion and extension required in the cat's hindlimbs in walking could be generated in the absence of sensory input from the hindlimbs. I t is now accepted that there are rhythm-generating centres in the spinal cord, one for each limb. The way in which the groups of muscles (flexors and extensors) co-ordinate their activities in an individual limb and the co-ordination of the hindlimbs and forelimbs (of the cat) or two limbs (bipedal animals) or six limbs (of the cockroach) is not fully understood. PEARSON and ILES4 suggested that a group of interneurons in the spinal cord (the

flexor burst generator) at the appropriate lumbar/sacral level activated the flexor motor neurons and simultaneously in- hibited the extensor motor neurons. When the flexor burst generator became inactive due to a slow intrinsic inactivation (or an inhibitory sensory signal) the extensor motor neurons became disinhibited and extension of the limbs took place. (It is assumed that i t is known that the cycle through which each limb goes in one step is divided into a swing phase and a stance phase, and that flexion takes place in the swing phase and extension in the stance phase.) S H l K and ORLOVSKY’ discuss in detail various hypotheses which could explain the spinal automatism of stepping and conclude that none satisfactorily explains all the observed facts which they list.

MILLER and SCOTT^ suggested a model of the spinal locomotor generator in which two sets of a-motorneurons, Renshaw cells and Ia-interneurons, one set for flexor and one for extensor muscles, are sufficient to explain stepping movements without the stimulus of an afferent input or descending pathways. They also used their model to explain standing, decerebrate rigidity and spasticity.

EIDELBERG et al. ’, in their experiments on Macaque monkeys, concluded that spinal cord generators cannot be activated in primates without stimulation from the reticulospinal and vestibulospinal tracts in the ventrolateral part of the spinal cord. However, they rejected the idea that these spinal generators are absent in primates.

The observations on the movements of the upper limbs during human walking by JACKSON er d 8 are relevant to the theory of spinal rhythm generators. They found that if the upper limbs were held voluntarily against the trunk, walking was much easier than when the limbs were strapped to the trunk, and that walking with the right upper limb swinging forward at the same time as the right lower limb went forward was difficult. It appeared that deliberate interference with the generators led to difficulty in walking, and they concluded that the movements of the upper limbs during walking in man constitute a retention of the pattern of activity essential for progression in quadrupeds. This concept of the co-

ordination of the movements of the upper and lower limbs in man was put forward by COSTAGLIOLA9.

Descending pathways The spinal cord generators are acted on by two types of neurons in the brainstem. The first is slow-acting and monoaminergic and acts on the interneuronal network which becomes autonomous in relation to rhythmic stepping”. The cell bodies of these descending neurons are in the raphe nuclei in the reticular formation of the pons and medulla. Dorsal reticulospinal tracts may also be involved in activating these autonomous locomotor centres.

The reticulospinal, vestibulospinal and rubrospinal neurons are maximally active in the swing phase (flexor muscles) and the vestibulospinal at the beginning of the stance phase (extensor muscles). In addition, the vestibulospinal and reticulo- spinal neurons influence the ipsilateral limb and the rubrospinal the contralateral“.

The rble of these descending tracts is different from that of the monoaminergic and dorsal reticulospinal tracts. The former do not affect the frequency of the stepping, or the duration of the stance and swing phases. They do affect the electro- myographic activity of the muscles involved in stepping.

The corticospinal tract is regarded as functioning in a manner similar to that of the rubrospinal and vestibulospinal tracts.

Cerebellum The cerebellum is not essential for the generation of the stepping rhythm, which is controlled by the spinal cord rhythm generators, but ITO’’ suggested three other rbles. First, it contributes to the adjustment of the timing of the movements of the limbs. Cooling and ablation of different parts of the cerebellum altered the duration of the swing and stance phase. Second, it influences inter-limb co- ordination. This is mediated through the reticulospinal neurons and is dependent on the peripheral feedback from the position of the limbs. Finally, various reflex activities may be made compatible with locomotion by the cerebellum which can adjust the magnitude and timing of various spinal reflexes and the responses to tonic labyrinthine reflexes.

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The cerebellum produces its effects through the reticulospinal, vestibulospinal and rubrospinal neurons which show a dim- inution or loss of modulation of discharge in relation to the rhythm of stepping if the cerebellum is removed5. Because it receives an enormous amount of information about the peripheral motor apparatus, including the spinal generators, ARCHAV- SKY et al. l 3 suggested tha.t the cerebellum selects the data required for regulating the transmission of signals from one part of the nervous system to another.

Subthalamic and mesencephalic motor regions W A L L E R ’ ~ found that stimulation of the subthalamic region evoked running move- ments in the limbs of the lightly anaesthetized cat suspended in a hammock. ORLOVSKY15 produced a similar effect in thalamic cats. Destruction of the sub- thalamic motor region on both sides eliminated voluntary locomotion. How- ever, if the midbrain locomotor region is stimulated, co-ordinated walking and running take place. SHIK and ORLOVSKY’ suggested that the subthalamic region is responsible for the initiation of locomotion only as part of goal-directed behaviour, such as searching and hunting, and that this motor region is similar in function to other parts of the hypothalamus related to behavioural and emotional manifestations.

The mesencephalic motor region is a limited area of the reticular formation of the midbrain, the nucleus cuneiformis, just below the inferior colliculus. If the brain is cut above the midbrain the animal cannot walk, but stimulation of the region referred to results in normal locomotion with proper interlimb co-ordination. Increased stimulation results in increased speed of walking which becomes trotting and finally galloping.

STEEVES and JORDAN^^ found that locomotion in the cat could not be evoked by stimulation of the mesencephalic locomotor region following bilateral lesions of the ventrolateral quadrants of the spinal cord. I t appears that this motor region produces locomotion by activation of pontine and medullary reticulospinal pathways which descend in the ventro- lateral quadrants of the spinal cord.

It has been suggested that the main

function of the mesencephalic motor region is to produce more powerful locomotion and that its activity in the animal at rest is suppressed by other centres.

Thalamus, basal ganglia and cerebral cortex None of these structures is regarded as essential for the rhythmic stepping movements of walking on a flat surface. They are required for the initiation of locomotion and changes in the locomotor pattern, such as are needed to cope with meeting an obstacle or sudden changes in velocity or direction. The precise r61e of the thalamus is difficult to evaluate, but it must be involved since it receives much of the peripheral input from the limbs, directly or indirectly, and is connected with the cerebellum, the motor cortex, the reticular system and the basal ganglia.

MARTIN” has written at some length on the effect of Parkinson’s disease on posture and gait. He suggested that although diseases of the basal ganglia do not affect the stepping mechanism, there are disturbances of posture, such as fixation, equilibrium and righting, and these result in patients standing still, unable to make the necessary postural changes required for walking. He associated these defects of posture with disease of the globus pallidus. Some patients with Parkinson’s disease cannot control their running forwards and this he associated with lesions of the caudate nuclei.

In decerebrate animals the walking movements of each limb and the co- ordination of the limbs are not affected and the animals can respond purposely to an external stimulus such as a whistle.

Sensory influences Although there is general agreement that the spinal generators can function without any sensory input so long as the movements involved in locomotion follow the basic stereotyped pattern, even in the spinal animal there are sensory influences on gait. G R I L L N E R ~ ~ considered the various sources of such an input. In the spinal animal afferents from the hip, either the extensor muscles or joint capsule, determine the switch from extension of the limb to flexion. Unspecific stimuli, such as squeezing the tail, increase the rate and

force of the movements of the limbs. A tactile stimulus in the flexion phase to the dorsum of the foot in the chronic spinal cat results in increased flexion. This is thought to explain what happens when an obstacle is touched in the flexion phase.

In the intact animal i t has been suggested that joint receptors not only act on spinal neurons but also affect the motor cortex via the dorsal columns and thalamus, and in this way affect the gait1’. DIETZ et a1.20.21 associate the locomotor reactions to stumbling in man with group I1 and group I11 afferents, which reflexly produce the appropriate motor reactions.

Input from the vestibular apparatus, to which reference has already been made, affects locomotion at reflex levels. The vestibulospinal tract is part of the automatic system which provides co- ordination of limb movements and maintenance of equilibrium. Vestibular neurons, as well as spinocerebellar, spino- olivocerebellar and spinoreticulocerebellar tracts go to the cerebellum. With all this input one can appreciate the suggestion that the cerebellum selects the appropriate information required and then co- ordinates the muscle activity involved in locomotion.

Visual input must play a very important part in locomotion in everyday situations, such as taking action to avoid an obstacle. THOMSON~~ showed that for a limited period of time (8secs) and distance (6m) subjects could memorize the arrangement of obstacles so that they could be avoided if blindfolded.

In summary, there are spinal cord generators for each limb. These generators

Re1erenL.e.r I . Sherrington. C. S. (1910) ’Flexion-reflex of the

limb, crossed extension reflex, and reflex stepping and standing.’ Journal of Ph.vsiolog), (London). 40, 28- 121.

2. Brown, T. G. (191 1 ) ‘The intrinsic factors in the act of progression in the mammal.’ Proceedings of the Royal .Yoi,irry, 1.ondon. .Yrrirs B. 84, 308-3 19.

3. Grillner, S., Zangger. P. (1974) ‘Locomotor movements generated by the deafferented spinal cord.’ Acra Physiologica Srandinavica. 91.

4. Pearson, K . G.. Iles, J . F. (1973) ‘Nervous mechanisms underlying intersegmental co- ordination of leg movements during walking in the cockroach.’ Journal of Ewperimenral Rio1og.y. 58, 725-744.

5 . Shik. M. L., Orlovsky, G. N . (1976) ‘Neuro-

38A-39A.

are co-ordinated by interneurons and activate the motor neurons supplying the muscles which move the limbs. The alternate flexion and extension of each limb and the limb sequence in stepping are determined by the generators. It is suggested that this arrangement is found in a wide range of animals, from cockroaches to man. Support for this concept comes from MARSDEN et who, in studying the use of peripheral feedback in the control of movement, suggested that many motor programmes are ‘hardwired’ into the infant’s nervous system.

These generators are acted on by sensory pathways and a number of descending neurons. The latter are divided into monoaminergic reticulospinal pathways, with slow conducting axons acted on by subthalamic and mesencephalic motor centres, and fast conducting pathways, which include other reticulospinal tracts and the vestibulospinal and rubrospinal tracts. The motor centres and mono- aminergic pathways set in motion the stepping and influence its frequency. The other pathways, influenced by the cerebel- lum, basal ganglia and cerebral cortex, determine the response to factors which interfere with regular stepping, for example, the type of surface being walked on, obstacles and change of direction.

JACK JOSEPH Professor Emeritus

Department of Anatomy, Guy’s Hospital Medical School, London SEI 9RT. (1 7 Greenfield Gardens, London NW2 IHT).

physiology of locomotor automatism.’ Ph,ssro- logical Reviews. 56, 465-501.

6. Miller, S . , Scott, P. D. (1977) ‘The spinal loco- motor generator.’ Experimental Brain Research,

7. Eidelberg, E., Walden, J . G., Nguyen, L. H. (1981) ‘Locomotor control in Macaque monkeys.’ Brain. 104, 647-663.

8. Jackson, K . M., Joseph, J., Wyard, S. J . (1983) ‘The upper limbs during human walking. Part 2. Functional.’ Elecrroencephalographv and Clinical Neurophysiology. 23,435-446.

9. Costagliola. J . (1977) ‘Pourquoi I’homme balance-t-il les bras en marchant?’ Journal of Agressologie. 18, 119-129.

10. Lundberg, A. (1969) Reflex Conrrol of Srepping. Oslo: Universitetsforlaget.

11 . Orlovsky, G. N. (1972) ‘The effect of different

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descending systems on flexor and extensor activity during locomotion.’ Brain Research,

12. Ito (1984) The Cerebellum and Neural Control. New York: Raven Press.

13. Archavsky, Yu. I . , Gelfand, 1. M., Orlovsky, G. N. (1983) ‘The cerebellum and control of rhythmical movements.’ Trends in Neuroscience, 6,417-422.

14. Waller, W. H. (1940) ‘Progression movements elicited by subthalamic stimulation.’ Journal of Neurophysiology, 3, 300-307.

15. Orlovsky, G. N. (1969) ‘Spontaneous and induced locomotion of the thalamic cat.’

40, 359-37 I .

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Biophysics, 14, 1154-1 162. 16. Steeves, J . D., Jordan, L. M . (1980)‘Loealisation

of a descending pathway in the spinal cord which is necessary for controlled locomotion.’ Neuroscience Letters, 20, 283-288.

17. Martin, J. P. (1967) The Basal Ganglia and Posture. London: Pitman.

18. Grillner, S. (1975) ‘Locomotion in vertebrates:

Hunting Disease

on’s

HUNTINGTON’S disease is a heritable, chronic neurodegenerative disease which affects both sexes and may be expressed from early childhood to advanced age. The disorder bears the name of GEORGE HUNTINGTON, who provided a critical clinical description in 1872I. Huntington documented transmission through suc- cessive generations of natives of Long Island, New York. All affected by the disorder were descended from ancestors who had emigrated from East Anglia to the New World in 1649. The disorder is now widely dispersed about the globe. I t is best known in Caucasian populations, among whom the prevalence is approximately 1 in 10,0002. It is probable that all examples of the disorder have derived from the lineage originating in East Anglia. At any rate, there are no satisfactorily documented examples of new mutations3.

Clinical expression Clinical manifestations Penetrance of symptoms of Huntington’s disease is 100 per cent, assuming that life is not terminated prematurely4. Expression is highly variable, both with respect to clinical manifestations and age of onsets. Chorea, a cardinal manifestation, is

central mechanisms and reflex interaction.’ Physiological Revieus, 55, 247-304.

19. Tracey, J. D. (1980) ‘Joint receptors and the control of movement.’ Trends in Neuroscience. 3. 253-255.

20. Dietz, V., Quintern, J . , Berger. W. ( 1 9 8 4 ~ ) ‘Corrective reactions to stumbling in man: functional significance of spinal and trans- cortical reflexes.’ Neuroscience Lerrers. 44, 131-135.

21. Dietz, V., Quintern, J . , Berger. W. (1984b) ‘Cerebral evoked potentials associated with the compensatory reactions following stance and gait perturbation.’ Neuroscience Lerrers. 50,

22. Thomson, J. A. (1980) ‘How d o we use visual information to control locomotion?’ Trend.s in Neuroscience, 3, 247-250.

23. Marsden, C. D., Rothwell, J . C., Day, B. 1. (1984) ‘The use of peripheral feedback in the control of movement.’ Trends in Neuroxienw.

18 1-186.

7. 253-257.

generally initiated by flickers in the fingers and tic-like grimaces of the face. With time, higher-amplitude ‘dance-like’ move- ments disrupt voluntary actions of the extremities and interfere with gait. Speech becomes dysrhythmic. Characteristically the patient is hypotonic, though reflexes may be augmented and there may be clonus. Voluntary gaze is disturbed early. In particular, saccades may be irregular, of prolonged latency and may require an initial blink for their initiation6, ’. Loss of opticokinetic nystagmus is characteristic after a decade of progressive disease. Whereas chorea is the most typical motor abnormality, a contrasting picture domin- ated by rigidity, bradykinesia and dystonic postures, the ‘Westphal variant’, is a well recognised but less common pattern*. Generalized seizures, though not common, may also occur.

Although chorea and other motor disabilities are the most readily recognized, they may be neither the earliest to appear nor the most disabling manifestations of Huntington’s disease. Psychological dis- turbances and personality change are the initial manifestations in well over 50 per cent of affected cases9* I ” . Symptoms consistent with a depressive state are most frequent and include despondency, out- bursts of anger, decreased attentiveness and decline in work effectiveness. Cog- nitive and memory impairments typically progress concurrently with the affective disorder.