Influences of movement detectors on pyramidal tract neurons in primates.

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Annu. Rev. Physiol. 1976.38:121-137. Downloaded from www.annualreviews.org Access provided by Texas Christian University on 01/31/15. For personal use only.

Copyright 1976. All rights reserved

INFLUENCES OF MOVEMENT

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DETECTORS ON. PYRAMIDAL TRACT NEURONS IN PRIMATES R. Porter Department of Physiology, Monash University, Clayton, Victoria, Australia 3168

INTRODUCTION In his Ferrier Lecture, Phillips (42), commenting on the report by Evarts (12) that 'pyramidal tract neuron discharge in the conscious monkey was more related to the force to be generated in particular muscle groups than to other aspects of movement performance, noted:

One may hazard the speculation that the increased discharge of the PT (pyramidal tract) cell [when more force was required to produce a particular displacement], was in response to a signal of mismatch between "intended" and actual displacement. Whether this signal is a crude one from the muscle spindles, or whether the mismatch has been computed by the cerebellum is still unknown; nor, in this experiment, can the contribution of joints, skin and vision be assessed. But however "instructed", the CM (cortico-motoneuronal) projection would transfer the "instruction" for increased force to the alpha motoneurons with maximum directness. If the CM projection is indeed part of a control loop, new sense is made of the old observation that "voluntary" movements of a monkey's arm are grossly impaired by deafferentation (31), when responses to cortical stimulation are unaffected (40,51). It may ·well be that the most important function of fusimotor co-activation in the case of the hand is to maintain the inflow of information of muscle length to the cortex and cerebellum. This speculation raises a number of questions concerning the function of pyra midal tract neurons and other precentral cells in movement performance. Recent evidence related to this concept of involvement of feedback about movement perfor mance in modifying the "pyramidal command" for movement (Houk 28) is re viewed here. Situated as they are, only one or a few synapses removed from the motoneurons whose orderly recruitment is required for skilled movement, pyra121


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midal tract neurons could be sites of convergence for a variety of signals relevant to motoneuron output. But, in evaluating the concept of adjustment of the pyramidal tract output of a control system for movement performance in the light of feedback information about that performance (derived from peripheral receptors in the moving part or from vision), it is necessary not only to demonstrate that the feedback converges onto the pyramidal tract neurons, but that it is effective and appropriate for the required adjustments. Phillips (42) focused attention on the possibility that muscle spindles play a dominant role in a transcortical servo-loop, and some progress has been made toward evaluating that concept. Other experimental work.has attempted to examine the "compensation" that results from a disturbance of movement perfor mance (l5, 38). This review examines the progress made in collecting the evidence necessary for the thorough evaluation of the concept propounded by Phillips and quoted above. Only a few of the relevant pieces of scientific work have been selected for inclusion in the commentary. These selected investigations are representative of the studies relating to the problem posed in the opening paragraph. The reader may find it more useful to examine these in some depth, rather than to attempt to cope with a relatively undigested list of all the papers recently published on this topic. A more extensive bibliography can be compiled readily, using the work examined here as a source of references. A number of separate questions may be extracted from the paragraph quoted from Phillips. 1. Does information from muscle spindles (possibly about mismatch between "in tended" and actual displacement) have access to pyramidal tract neurons whose activity is associated with that displacement? 2. Do other systems capable of detecting or measuring movement or displacement (afferents from joints, skin, and vision) also converge onto these same pyramidal tract neurons? 3. By which central nervous pathways does this information reach the pyramidal tract neurons? 4. What changes in pyramidal tract output are produced by purposely disturbing an intended movement (and so activating detectors of position and movement)? Are these changes in an appropriate direction for maintaining the intended movement in spite of the disturbance? Do the changes occur early enough to be useful to the animal in the normal performance of a smooth natural movement? Can normal performance be carried out in the absence of these changes? A number of these questions have been examined in a variety of animal species. Often the assumption has been made that the detection of a response to a distur bance indicated a competent feedback loop operating in servo-compensation for the disturbance. Yet the nature of the experiment itself invalidated that conclusion because no compensation occurred or because no relation between feedback and compensation was established. In the present review, the examples are drawn almost exclusively from experiments on primates; only occasional reference is made to the important studies on afferent projections to pyramidal tract neurons of the cat or other animals (see 5).

AFFERENTS TO PYRAMIDAL TRACT NEURONS

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PROJECTIONS TO PYRAMIDAL TRACT NEURONS FROM MUSCLE SPINDLE AFFERENTS

Evoked potentials may be recorded on the surface of both pre- and postcentral cortex when deep tissue is stimulated (1, 37), or when muscle nerves are activated with weak shocks (4). But these evoked potentials could have been generated in zones removed from the recording site. Studies of the discharges of individual neurons in the monkey's cerebral cortex led Powell & Mountcastle (45) to suggest that the buried cortex between the principally "motor" precentral gyrus and the principally "sensory" postcentral gyrus was a region of transition that received "a heavy projection from deep tissues." This view has since received strong support

from the studies of Phillips, Powell & Wiesendanger (43). In baboons anesthetized with nitrous oxide and oxygen together with chloralose, stimuli were delivered to muscular branches of nerves supplying the hand and forearm, while the cerebral cortex both in front of and behind the central sulcus was explored with microelec trodes. Both the evoked "field" potentials and the discharges of individual neurons responding to these muscle nerve shocks were localized within area 3a. The majority of units discharged between 5 and 10 msec after the group I volley, set up by weak stimulation of the nerves, entered the spinal cord along dorsal roots. Neurons in area 3a responded to a brief pull on muscle tendons or to brief periods of vibration of

4. Weak shocks applied to muscle nerves did not evoke field potentials or cause the discharge of neurons in area 4, an d stimulation of neurons in area 3a did not alter the thresholds for minimal muscle responses caused by intracortical microstimulation in area 4 (43). The conclusion must be that, under the particular anesthetic conditions used in these baboons, no short-latency powerful excitatory projection from muscle spindles could be demonstrated to influence neurons in area 4. It is also of interest to note that the cells in area 3a, activated by group I volleys in muscle nerves, were not pyramidal tract neurons (they were not sending their axons out of the cortex through the pyramidal tracts). So, area 3a itself was not the reflex center of a long-loop reflex for adjustment of pyramidal tract output to the mismatch between intended and actual muscle length that could be detected by muscle spindles. But other evidence ex iste d for a projection of influences from muscle receptors to individual neurons in the precentral motor cortex. Albe-Fessard & Liebeskin d (3) described influences on motor cortex cells from peripheral stimuli. They noted that a large majority of motor cortex cells could be driven by passive movements of limbs (not by light tactile stimulation of the skin). These effects were considered to arise in muscles because traction on muscle tendons and light pressure on denuded

tendons. No such early responses were recorded in area

muscles influenced the cells in the cortex. The monkeys used in these experiments

were also anesthetized with chloralose. The latencies of the responses of motor cortex neurons could not be measured accurately in these experiments, nor could it be concluded that the recordings were from neurons destined to send their axons into the spinal cord.

Further evidence for the muscular o rigi n of some of the influences projected to the motor cortex was obtained by Albe-Fessard, Lamarre & Pimpaneau (2). These authors stimulated fusimotor fibers to the semitendinosus muscle of critically cura-


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rized monkeys. Under these conditions, the dose of d-tubocurarine was adjusted so that stimulation of muscle nerves could still activate the more resistant intrafusal fibers of muscle spindles, even though neuromuscular transmission to extrafusal muscle fibers was totally paralyzed and no overt contractions of the muscle occurred. The stimulation therefore activated muscle spindle afferents without causing muscle contraction or movement of joints. It also produced discharge of neurons in the motor cortex. Wiesendanger (60) examined the responses of precentral neurons in baboons and monkeys anesthetized with nitrous oxide and oxygen together with chloralose. He was able to demonstrate that electrical stimulation of muscle nerves caused excita tion of proven pyramidal tract neurons in the precentral gyrus. Although a few "minimal" responses were obtained with stimuli at 1.4 times group I threshold, most units studied required repetitive shocks of 2-3 times group I threshold, and the unit could be driven by one or more muscle nerves. The mean response latencies of pyramidal tract cells measured from the first peak of the compound action potential entering the spinal cord along dorsal root fibers were of the order of 20-25 msec, although nonpyramidal tract cells could be activated at shorter latencies. Wiesendanger also found, in contrast to Albe-Fessard and her colleagues, consid erable convergence onto individual pyramidal tract cells from both muscle nerve afferents and skin nerve afferents when these were activated by electrical shocks (Albe-Fessard et al had reported their observation for natural stimulation). He reasoned that the strong stimulation of muscle nerves required to activate pyramidal tract cells, the long latencies of the responses, and the insensitivity of the discharges of these pyramidal tract neurons to intravenous injections of succinylcholine which excites primary endings indicated that afferents from secondary, rather than from primary, endings of muscle spindles must be responsible. Passive manipulation of the finger and wrist joints was an adequate stimulus for discharge of pyramidal tract neurons, and it was reported (60) that the discharges produced by passive manipulation of joints were tonic in character, similar to those reported by Albe-Fessard & Liebeskind (3). These movements could also have activated muscle afferents, and the tonic responses were considered to be consistent with an input from afferent fibers of secondary endings in muscle spindles. Hore et al (27) recorded from neurons in both area 3a and area 4 of the chloralose anesthetized baboon while they delivered ramps of stretch to hindlimb muscles. The results of their experiments suggest a convergence of inputs from both primary and secondary endings of muscle spindle receptors onto cells in these two regions. Units with the greatest sensitivity to length changes in the muscle were found in area 4, whereas units in area 3a often had little or no "static" response to maintained length of the muscle. Ve!ocity sensitivity, as detected by the dynamic index of the cortical unit when the muscle was subjected to different rates of stretch, was measurable for both units in area 4 and in area 3a, although the latter cells tended to have the greatest velocity sensitivity. In summary, pyramidal tract neurons and other cells in area 4 of the motor cortex have been shown to be influenced [excited in most experiments, but inhibited in some of the observations of Hore et al (27)] by afferent signals projecting to the central


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nervous system from muscles. This input reaches the motor cortex later than it is available to cells in area 3a and appears to have a more sustained effect on cells in area 4.


PROJECTIONS FROM RECEPTORS OTHER THAN THOSE IN MUSCLE

Although the experimental work described above establishes that projections from muscle afferents can influence pyramidal tract and other precentral neurons, a contribution from joint afferents, from tendon organs, or from skin receptors could have been involved in producing some of the responses observed. Fetz & Baker (20) examined the responses of a large population of precentral neurons in the "leg" area of conscious monkeys and found that 85% of these responded in a reliable and reproducible way to movement of one or more joints of the contralateral leg. Only a very small proportion of cortical neurons could be shown to be influenced by natural stimulation of the skin. Fetz et al (22) recorded the discharges of precentral neurons in relation to both active and passive movements of the elbow of conscious monkeys. About half of the cells studied responded only to one direction of passive movement (flexion or extension) and about one-third responded to movement in both directions. Cells that discharged during passive movement of the elbow in only one direction also re sponded when the animal performed active movements. Roughly one third of these cells discharged most strongly when the active movement was made in the same direction as the passive movement to which the cell responded. For roughly one third, the active movement with which the strongest discharge was associated was in the opposite direction and, for the rest, strong discharge of the cell occurred during active movements in both directions. The suggestion was made that there must be "a variety of input-output relations for precentral cells" receiving projec tions from elbow afferents (22). In the conscious cooperating animal, it has not been possible to dissect the contributions of muscle, tendon, skin, or joint afferents to the responses being studied. An impression gained from published work, as well as from observations in the author's own laboratory, is that when natural stimuli such as passive finger flexion are used, more definite, sustained, and reproducible responses of pyramidal tract and other precentral neurons are recorded in the conscious animal, compared with those reported for chloralose anesthetized monkeys. Interaction of influences from a variety of receptors in the moving part may occur more readily at a number of levels in the nervous system and produce a more pronounced effect in the absence of depression produced by anesthetic agents. It is certainly possible that the effects reported by Fetz and his colleagues represent additional influences of joint afferents (over and above those caused by stretching muscles) on precentral neurons. Evidence for a contribution of peripheral influences, other than those from the prime-mover muscles, in the natural discharges of pyramidal tract neurons came from the studies of Lewis & Porter (34), in which local anesthesia at the wrist was used to reduce the input from skin and joint receptors of the hand (and from the


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small muscles of the hand), while all the feedback from muscles in the forearm operating about the joints of the hand was left intact. For a small population of pyramidal tract neurons (roughly 10% of the total number studied), selected be cause they showed clear changes in activity with changes in the load to be moved, as well as a distinct relationship of their bursts of discharge to the timing of contraction of the prime-mover muscles, partial local anesthesia at the wrist pro duced an increase in activity of pyramidal tract neurons in relation to the same movement performance. But the cell could stili change its firing with a change in load (so feedback for this must either have come from intact receptors such as those in muscles or have been internal feedback related to the program of movement). Also the relationship between the cell's activity and the timing of muscle contraction generally was preserved; there was, however, a tendency for a longer period to elapse between the beginning of pyramidal tract discharge and the beginning of movement after the hand had been partially anesthetized. Goldring, Aras & Weber (23) drew attention to the fact that the afferent projec tions to the motor cortex are different in different animals and show differential sensitivity to anesthetic agents. They used transcortical recording of evoked poten tials in order to localize the inputs from peripheral nerves in the cat [see also the detailed analysis of inputs to cat PT cells by Towe & Tyner (59)], squirrel monkey, and man, and they compared observations made in the awake and the anesthetized states. More responses and a greater variety of influences were detected in the waking monkey than in the anesthetized monkey. Inputs from limited contralateral receptive fields (preserved in the anesthetized state) as well as long latency inputs from large fields, from ipsilateral zones, and of a "polysensory" nature (suppressed by anesthesia) could be defined. In man, studied with the same evoked potential methods, the responses were variable. In general, however, the afferent projections to the motor cortex of man were more limited and mostly contralateral. No responses to auditory stimuli were found in man or the monkey (although these were readily recorded in the cat). No evoked responses to visual stimuli were observed in any of the three species. A very limited number of observations have been made on the responses of individual precentral neurons in conscious man during active and passive limb movements (24). The majority of cells discharged only in association with active voluntary movements of the contralateral hand (opening or closing the fist on command), but a few discharged with active movement of either hand. Those cells showing a change in firing that preceded voluntary movement were also excited by the same movement when carried out passively by the observer. This observation held true also for cells whose discharge was related to movements of both hands these cells had bilateral receptive domains for passive movement. None of the cells was influenced by tactile stimulation (with a light cotton wisp) or by auditory stimulation (with a click). Goldring & Ratcheson (24) concluded from their study of a limited number of cortical units in man that the significant projection to the hand area of motor cortex in man differed from that in animals by being from the restricted region involved in the movement and by being concerned exclusively with movement detection. They concluded: "It appears that, in man, the function of



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processing diverse sensory inputs from the periphery, a function characterizing the motor cortex of the cat and, to a lesser extent, that of the macaque, has been relegated elsewhere" (24). These observations deserve prominence because they have been made in subjects most able to cooperate, to carry out a variety of movement tasks on command, to relax during passive manipulation, and to attempt exact copies of posture and movement without complex and prolonged training schedules. But the limited number of observations that can be made requires that conclusions be accepted with caution and that additional evidence for these conclu sions be sought in further experimental work. The absence of short-latency responses to visual stimuli of precentral neurons in the monkey and man is consistent with Evart's (16, 17) report that when monkeys were conditioned to make the same movement response to a visual signal or to a perturbation of the handle held by the animal, the responses of pyramidal tract neurons began much earlier following the mechanical stimulus to the hand (an interval of as little as 25 msec) than after the visual signal; the latency was then about 100 msec. The nature of the receptors responsible for the short-latency responses to a mechanical perturbation of the hand to be moved could not be deduced. But from the different responses evoked by different directions of the perturbation [push or pull of the hand (IS») and from the influence of prior instruction on the nature of these short-latency responses (I8), it might tentatively be concluded that stretch of muscles by the perturbation was in part responsible for the early effects. A contribution from joint afferents was also possible. The important conclusion from the experiments of Evarts & Tanji (18) was that, in the conscious animal, even the short-latency influences on pyramidal tract neu rons of a small passive movement of the hand could be remarkably modified by the training and instruction regarding the movement performance to be executed after delivery of this perturbation. Such modifications could have occurred by changes in fusimotor drive to spindle r-eceptors in central sensitivity to spindle influences. They could also account for variability in the direction of the responses of different individual neurons in a class behaving uniformly in other respects [as in relation to the one direction of active movement performance (22»). Short-latency influences produced by small perturbations of movement perfor mance by the arm or hand have been reported by Evarts (15), Porter & Rack (48), and Conrad et al (I0). The movement performance and its disturbance were quite different in each of these cases, yet the usual latency of the response of pyramidal tract neurons was remarkably similar (of the order of 25 msec as a minimum). This latency is also very similar to that reported from muscle nerve stimulation in anesthetized animals. As in those experiments, nonpyramidal tract neurons could be found that responded earlier to the disturbance. In all cases, the disturbance could have influenced muscle, joint, and skin receptors. The fact that pyramidal tract and other precentral neurons are influenced by a disturbance of movement performance as early as 25 msec after this disturbance is produced could mean that feedback about movement accomplishment plays a part in the modification of pyramidal tract output during movement execution and while the movement is still

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in progress. Other experiments will be required to demonstrate whether this early influence of peripheral receptors does exert a significant a movement once it has been initiated.


PATHWA YS INVOLVED IN PROJECTIONS FROM PERIPHERAL RECEPTORS TO PYRAMIDAL TRACT NEURONS

Although there is a wealth of evidence for connections to the motor cortex from thalamic nuclei, the role of projections from the spinal cord through these, either directly or via the cerebellum, has not been evaluated adequately in attempts to account for the results in primates reported above. Moreover, the contributions that cortico-cortical connections make to the afferent influences neurons have received little attention. In particular, it is not clear whether-and by what route-the very early infu l ences spindles on neurons in area 3a of the cerebral cortex are then relayed from that zone of cortex to pyramidal tract neurons in area 4. Asanuma & Fernandez (6, 7) studied the receptive fields of individual neurons in the ventrolateral nucleus of the thalamus in cats. A proportion of these cells could be shown to project to the motor cortex. The receptive fields differed markedly from those in the ventrobasal complex. No neuron in the ventrolateral nucleus could be activated from a circumscribed skin area localized on the contralateral side of the body. About half could be activated by pressure somewhere on the contralateral body surface, and it was suggested that the receptors responsible for this activation were located in deep structures. There was often no localized receptive field, but the authors reported their impression that about 90% of the cells that could be activated were influenced The other 10% could be influenced by pressure applied to any part of the body surface. The neurons in the ventrolateral nucleus of the cat were shown to project diffusely to the motor cortex [see also Strick (54)] or to project only to a narrow focus (7). Evidence has been produced suggesting that some cells of the ventrolateral nu cleus of the thalamus alter their discharge in relation to movement performance in the monkey and that they may demonstrate characteristic changes in their firing before the beginning of movement (13). But the relationship of peripheral afferent influences Lamarre (29) studied the responses of neurons in the ventrolateral complex of the conscious monkey. About half the cells from which they recorded could be in fluenced ventral parts of the complex. (Cells in the dorsal part of the ventrolateral nucleus were not responsive.) The responding cells could be activated by sharp pressure on deep tissues or by taps on tendons or muscles in one or several limbs "either contralateral or homolateral" (29). The latency of some of the responses to sharp taps on muscle was found to be 15-20 msec, and these cells increased their discnarge in advance of spontaneous movements.



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A recent preliminary study has been made of the effects of a sudden postural disturbance of the fingers on the discharges of ventrolateral nucleus neurons in conscious monkeys (P. Chau and R. Porter, 1975, unpublished observations). About half of a very small sample of neurons situated in the anterior division of the ventrolateral nucleus showed a clear response to a sudden small passive movement of the fingers. None of these responsive units exhibited changes in firing with the muscular activity and the development of force in the postural task itself. The sudden passive movement of the fingers could be controlled, so that a latency of response of each cell in the anterior division of the ventrolateral nucleus of the thalamus could be calculated; these latencies were all between 15 and 30 msec. Therefore some of these responses could have occurred before the activation of pyramidal tract cells in the motor cortex, first seen 20 or more msec after a similar disturbance under the same experimental conditions (48). The possibility exists, then, that there are cells in the ventrolateral complex of the thalamus that receive inputs from receptors capable of detecting disturbances of movement performance. These cells could be transmitting this information to pyra midal tract neurons after the effect of the disturbance has been "computed by the cerebellum" (42). But more exact information about the connections and precise responses to peripheral stimuli of the thalamic neurons is required to assess this possibility. Moreover, the differential connections of different parts of the ventrolat eral complex (32) need to be evaluated because the observations made so far seem to indicate that different populations of neurons behave in quite different ways in relation to movement or its disturbance. Meyer-Lohmann et al (39) found that reversible cooling of the dentate nucleus had no effect on early precentral responses to sudden displacements imposed on a learned elbow movement being carried out by monkeys. It seems unlikely therefore that a direct pathway from the cerebellar cortex through the dentate nucleus and ventrolateral nucleus of the thalamus is involved in the early response to perturba tions of movement. Moreover. although recordings have been made in the cerebel lum during movement (57.58) and during drug induced tremor (33), recordings of the activities of cells in the cerebellar nuclei following sudden disturbances of movement have not been made in primates. The possible contributions of a number of alternative and parallel pathways from peripheral detectors of movement to the motor cortex in producing the early responses of pyramidal tract neurons must be evaluated. Both pre- and postcentral neurons have been shown to change their firing during active movement performance, although the latter, on average, respond later than the former (14). Moreover, postcentral neurons responded to passive movements of the limb (52) in the conscious cooperating monkey. The short latency of responses of postcentral neurons to peripheral stimuli, the topographical organization of these projections. and the highly organized interconnections between pre- and postcentral regions of cortex in the monkey (41) would seem to suggest a function for postcen tral neurons in the feedback to pyramidal tract cells related to movement perfor mance or its disturbance.


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Cortical regions other than area 3a could be concerned in the receipt of informa tion from deep structures and subsequent projection of this to output neurons in the precentral gyrus. Powell & Mountcastle (45) reported that, while a majority of cells in area 3 of the postcentral gyrus were activated by cutaneous stimuli, 90% of the cells in area 2 were influenced by activation of receptors in deep tissues (fascia and joints). More recently, Burchfiel & Duffy (9) found cells in area 2 influenced by stimulation of musc1es as well as joints. Cells in area 2 had limited receptive domains and were influenced by movement of one joint only, sometimes through a part of its range of movement. Neurons in area 5 could also be influenced by joint movement (II) but, in their case, the receptive domain included a number of joints, as though these cells were engaged by convergent influences from other neurons, perhaps in area 2. Because area 4 in the precentral gyrus and area 6 and 8 in front of it are sent projections from the regions in receipt of inputs from peripheral receptors (both on the skin and in deep tissues), it is possible that corticocortical connections could subserve the delivery of information from movement detectors to the output pyramidal tract neurons (30). Although Sperry (53) indicated that interruptions of corticocortical connections by multiple transections of the sensorimotor cortex did not disrupt movement perfonnance, refinements of motor skills could be contributed by cor ticocortical influences. Recently, Haaxma & Kuypers (25) produced direct behavioral evidence for a function of corticocortical connections between visual receiving areas and the motor cortex in the "visual steering" of relatively independent hand and finger movements. Animals were required to orient the hand so that the thumb and forefinger could be inserted into a pair df grooves leading to a food well in a board. The appropriate grooves were painted white to distinguish them from other radially oriented grooves around the food well. All except these "correct" grooves ended blindly, and the orientation of the correct grooves could be changed from trial to trial, requiring changes in the attitude of the hand and the orientation of the finger and thumb if the food reward was to be retrieved. Following division of occipitofrontal connec tions, the animal's hand could be brought accurately to the general area of the target, but could not be adapted to the correct orientation of the white grooves without tactile exploration of the field. Yet the animal had no visual discrimination defect. . The defect was one of movement control, appropriately orienting the hand and fingers to the target under visual control. EFFECTIVENESS OF AFFERENT DISCHARGE PRODUCED BY DISTURBANCES OF VOLUNTARY MOVEMENT

When a voluntary movement such as flexion of the terminal phalanx of the thumb is unexpectedly obstructed, a human subject will demonstrate increased activity in the flexing muscles to overcome the obstruction-an appropriate and effective out put reaction. This had been conceived as a simple spinal reflex response to the obstruction until the experiments of Marsden, Merton & Morton (38) demonstrated that the delay between the disturbance and the response was considerably longer (of


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the order of 50 msec for the human thumb movement) than would have been expected for a simple stretch reflex. The longer latency could have allowed afferent signals about the disturbance of movement to be transmitted to higher levels of the central nervous system, perhaps including the motor cortex, and for the output of these centers to be changed appropriately for increasing the force of muscle con traction. Marsden, Merton & Morton assembled the evidence on which a long-loop response through the cerebral cortex might be implicated in this situation (38).


That the response was much more complicated than a stretch reflex was also

demonstrated by the observation that local anesthesia of the skin and joints of the moving thumb, without in any way affecting the action of the prime mover muscle or its muscle spindle afferents, abolished the response to sudden perturbations of the learned movement. To be effective then, the input system for detecting the distur bance of movement had to include information coming from the moving joint as well as information returning to the central nervous system from the operating muscles. Without this information, the subjects reported that more conscious effort was required to start a movement. Some authors have interpreted the observations made on pyramidal tract cells of monkeys in the light of the above findings in man. The discharges of cortical neurons that occurred with short latencies after a disturbance of a trained movement were described as part of a "load compensation" reflex (10). But it is not clear in all these cases that load compensation occurred, nor has the role of pyramidal tract neurons in load compensation been demonstrated. Animals could still be trained in a force development task after pyramidal tract section (26). The destinations of the pyra midal tract neurons from which recordings were made in the experiments involving disturbances of movement could not be discovered; they were assumed to be related to output centers in the appropriate region of the spinal cord. If the relationship between the discharge of pyramidal tract neurons and the development of force in recognizable and particular muscles was always as clearly proportional as for some of the small number of cells reported by Evarts (12), then an increase in firing of those cells following a disturbance of movement might be closely related to an increase in force to overcome the disturbance. But it is clear that such a relationship holds for only a small proportion of pyramidal tract cells (50) and that a more complicated relation is likely to exist between the discharges of most precentral cells and the force output of a group of contracting muscles. This makes it impossible to equate a burst of discharge in sampled pyramidal tract neurons with a load compensation response. Moreover, the direction of the effect (excitation or inhibition) exerted on individ ual pyramidal tract cells has not been shown to be related directly to the direction of movement with which the cell's firing was associated in active movement. This could be caused by the very complex nature of most of the movement tasks used, involving as they do co-contraction of very large numbers of widely distributed muscle groups. Alternatively, it could be that the relationship between discharge of cortical neurons and the movement is "plastic" (49). Then inputs from the periphery about the movement being executed might also be expected to vary with repeated performances, changing conditions, and previous responses. Schmidt, Jost & Davis

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(49) reported that approximately one third of precentral motor cortex cells had a changing (plastic) relationship with a stereotyped movement task. This plasticity may have been concealed in many of the observations made by others in which less attention was paid to trial by trial modifications in firing and more to overall patterns of activity as detected by averaging nerve cell discharges over many repetitions of a stereotyped task. But, under these conditions, others have concluded that the average responses of pyramidal tract neurons in the conscious monkey occur in fixed temporal relationship to the movement task and presumably to the contractions of


some muscle groups involved in that task (46, 47). Certainly some pyramidal tract neurons discharge in a very regular and reproducible manner in association with every repetition of a stereotyped motor task, and with well-defined temporal rela tionship to muscle contractions in that task. This relationship is preserved without change through very large numbers of repetitions. The evaluation of the effectiveness and appropriateness of inputs to the motor cortex must be influenced by the modifiability of the discharges recorded from cells in this zone. Fetz & Finocchio

(2 I) demonstrated that the relationship

between cell

firing and muscle contraction could be influenced by operant conditioning in the monkey. But, even so, some correlations were more resistant to change than others, and it might be concluded that, if the correct pairing of pyramidal tract cell and muscle (or collection of motor units) were examined, strict and relatively fixed correlations between these perhaps rare but potentially important tightly coupled pairs could be demonstrated. Tight coupling between some pyramidal tract neurons and some motoneurons exists through the corticomotoneuronal system (8, 44). Modifiability of the influences of peripheral feedback concerning disturbances of movement has also been demonstrated and referred to above ( 18). Depending upon the direction of the movement required to be made by the animal following a sudden disturbance of the hand and arm, responses of pyramidal tract cells to this distur bance could be enhanced or suppressed. Even when the animals had not been trained to carry out some movement performance following the peripheral disturbance (48), it may still have made a particular response that was not observed, or it may inadvertently have been conditioned to produce changes of cortical cell firing ( 19). . With appropriate conditions for reward, monkeys may change the firing of precen tral cortical neurons, including pyramidal tract cells, without overt responses in muscles whose electrical activity is being sampled ( 19, and E. Fetz, personal com munication). One of the greatest problems in the assessment of the responses of motor cortex cells to feedback from peripheral detectors of movement lies in the passive manipu lation of the limb and the activation of movement detectors in conscious monkeys. Even with prolonged periods of training, it is difficult to achieve relaxation of the animal's limb to a degree at which the movements could really be called "passive." Moreover, it is very difficult to assess small changes in muscle tone or subtle adjustments of posture that the animal may produce in association with the manipu lations of the limb. These self-initiated adjustments may be as potent as the passive movements in causing changes in firing of the precentral neurons. Such effects are



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much less likely to influence the short-latency responses to sudden, unexpected, and randomly timed disturbances of the position of the limb. But they could influence the more prolonged, sustained, later responses that have been shown to be modified by reversible interruption of pathways transversing. the dentate nucleus (39). The need for peripheral feedback about movement accomplishment has been challenged by the observation that tasks requiring graded performance of force development could be l earned and performed after section of dorsal root fibers conveying input from the limb to the central nervous system (55). But when a trained rapid flexion movement of the forearm of a squirrel monkey was analyzed in detail before and after dorsal root section, the results left "no doubt that the normal patterning of the motor output to the agonist and antagonist is strictly dependent on sensory input data, at least during fast ballistically initiated move ments. In particular, they exclude that even for a learned motor task the output to the agonist and antagonist is pre-programmed centrally" (56). Experiments of this sort do not yet provide information about the central nervous level at which the dorsal root input influences the pattern of muscle contraction involved in the task and they do not indicate whether the cerebellum or cerebral cortex are involved. The EMG changes that resulted from dorsal root section could have been caused in large part by alterations in excitability at a spinal cord level. But the fact that modifications were evident even in a very rapid ballistic movement must argue for some influence of peripheral receptors. In a slowly evolving skilled movement, comparison between actual and intended movement may be even more important. A more significant evaluation of the function of peripheral feedback in the perfor mance of movement is likely to be obtained by limited interference with particular aspects of potential movement detection (such as blocking of joint afferents) than by section of dorsal roots. One must presume that both central direction and peripheral feedback are in volved in normal movement performance. The peripheral feedback may be compli cated in its origin and it may produce generalized or localized effects (or both simultaneously). Although most experimental work has concentrated on the excita tory effects of activation of peripheral receptors, inhibitory actions have also been revealed and these could be extremely important in a localizing function for the influences that reach pyramidal tract cells from peripheral receptors. But the rela tionship between movement and sensation of movement may be one of the most important factors to control in assessing the influence of peripheral feedback. The ' effect produced may depend very largely on whether the animal is truly passive during the manipulation of its limb or whether it assists or opposes this movement with some active muscle contraction. Just as different sensations may result from the same moving stimulus, depending on whether the stimulus is moved or whether the stimulus is stationary and the receiving surface is moved actively past it, so cells in the motor cortex may respond differently to the same peripheral stimulus under passive or active conditions. In many experiments, these conditions cannot com pletely be controlled.


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A number of the observations that relate stimulation of receptors in the periphery to the presumed functional relationship between pyramidal tract cells and move·· ment appear to suggest a positive feedback effect. A number of investigators hav(: reported that passive movement of a limb or joint in a given direction is effective in causing discharge of a pyramidal tract cell when the displacement is made in the: same direction as that with which the cell's firing was associated during active movement. That this may be the case for only some precentral cortical cells is suggested by the findings of Fetz et al (22). But the proposal of a positive feedback from movement detectors deserves further examination. In one special instance, positive feedback from peripheral receptors seems to play an important functional role. Lund & Lamarre (36) examined the discharges of neurons in the lateral parts of the precentral cortex during jaw movements which occurred rhythmically as monkeys chewed food. They found that cells in this region could be related to the movement performance and also responded to passive movements of the jaw; loads that aided jaw opening increased the discharge of units that fired with active jaw opening movements. Some "jaw closing" cells seemed to receive inputs from receptors within the mouth and were responsive to pressure on the teeth. It was suggested that these neurons might participate in the control of force of jaw closure when this closure was opposed by a resistance between the teeth. Lund & Lamarre (35) reasoned that if cortical neurons controlling the force of contraction of jaw closing muscles receive positive feedback from receptors in the periodontal membrane, then elimination of this feedback should reduce the force of voluntary biting. This possibility was tested in a group of human subjects whose bite was monitored with a strain gauge between the teeth and with electromyograms. After infiltration of local anesthetic around the roots of the upper and lower premo lar teeth on one side, there was a fall in the voluntary applied force that could be developed in the bite on that side. This then recovered as the local anesthetic effect declined. Control injections around contralateral teeth not involved in the bite did not affect the force development. In this case then, some detectors of the movement performance (probably recep tors in the periodontal membrane) could have been involved in positive reinforce ment of the movement performance by stimulating increased activity of cortical neurons associated with biting. The reinforcement could have had an appropriate and effective influence because removal of it by local anesthesia in the vicinity of the receptors led to a reduction in the capacity to produce a maximum voluntary force output. Further analysis of this important question of the function of peripheral feedback will require more evidence on a number of matters referred to above. We are not able to give a quantitative account of the stream of information that flows into the central nervous system during the execution of a simple movement such as flexing the index finger. The contributions made to this information by different classes of receptors and its significance at spinal or supraspinal levels are, at present, largely speculative. But methods exist for the experimental study of movement detection. The intelligent application of these should lead to a better understanding of the relevance of movement detectors for movement performance.


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Diffusion tensor imaging of pyramidal tract reorganization after pediatric stroke.

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