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Single unit recording in the caudate nucleus during sessions with elaborate movements in the awake monkey
Brain Research, 71 (1974) 337-344 © Elsevier ScientificPublishing Company, Amsterdam - Printed in The Netherlands
337
Colloque C.N.R.S. no. 226 Comportement moteur et activit6s nerveuses programm6es Aix-en-Provence, 7-9 sept. 1973
S I N G L E U N I T R E C O R D I N G 1N T H E C A U D A T E N U C L E U S D U R I N G SESSIONS W I T H E L A B O R A T E MOVEMENTS IN T H E A W A K E M O N K E Y
PIERRE BUSER*, G. P O U D E R O U X AND J. M E R E A U X
Laboratoire de Neurophysiologie comparde, Universitd Paris VI, 75230 Paris Cddex 05 (France)
SUMMARY
Unit recordings were performed in the caudate nucleus o f awake macaques. Animals were maintained in a restraining chair and had been trained to perform various types o f elaborate movements to obtain food-reward. Three types of movement were studied: (a) natural, large gestures of grasping solid food (peanut) from a tray and bringing it to the mouth; (b) small amplitude lever-pressing movements for fluid reward (fruit juice), mainly involving distal segments (fingers, wrist); (c) same as (b), but involving essentially proximal musculature, and consisting o f an ample isotonic pulling with arm and shoulder. Units were recorded before and during each of the preceding types of movements (but in different animals). Results indicate that: (1) caudate cells were encountered in all 3 cases which were accelerated during different stages o f the movement; (2) more cells were activated in situations (a) and (b) than (c); (3) very few cells displayed inhibition instead of excitation; (4) among cells modified during movement, very few were also accelerated through passive flexions or extensions of the forelimb; (5) some caudate cells were also clearly activated through various visual or auditory intercurrent stimuli, probably arousing the animal's attention.
RI~SUM~
On a effectu6 des d6rivations unitaires dans le noyau caud6 de macaques ~veill~s et conscients, maintenus en chaise, et dress6s A effectuer un mouvement du membre * Also with previous collaboration of Drs. A. Kitsikis, L. Angyan, T. Wishart and B. Faucheux.
338
P. BUSER
ant6rieur pour obtenir de la nourriture. Trois types de mouvements ont 6t6 adopt6s: (a) saisir un aliment solide (cacahou6te) sur un plateau, puis le porter/l sa bouche (geste ample et complexe); (b) appuyer sur un levier, d'un mouvement limit6, int6ressant essentiellement les extr6mit6s distales (doigts et poignet) pour d6clencher un distributeur de liquide; (c) effectuer une traction, principalement h I'aide des segments proximaux, 6galement pour actionner le distributeur de liquide. Des unit6s ont pu &re recueillies au cours de ces 3 types d'op6rations motrices. Les r6sultats se r6sument ainsi: (1) dans les 3 situations exp6rimentales des cellules caud6es ont 6t6 isol6es, qui 6taient acc616r6es pendant le mouvement; (2) le nombre de cellules activ6es s'est r6v616 plus abondant dans les situations (a) et (b) que dans la situation (c); (3) tr6s peu de cellules ont t6moign6 d'une inhibition (au lieu d'une excitation); (4) parmi les cellules modifi6es pendant le mouvement actif, tr6s peu furent 6galement activ6es par une mobilisation passive du membre ant6rieur correspondant: (5) certaines cellules caud6es ont r6pondu - - en l'absence de mouvement - - / i des stimulus intercurrents visuels ou acoustiques, probablement susceptibles d'6veiller l'attention de l'animal.
The participation of the caudate nucleus in motor elaboration remains a matter of discussion and controversy. A considerable number o f studies based upon behavioral4, 5,1a,1~ or electrophysiologicaP °,~7 observations have suggested that it exerts an 'inhibitory' action; some authors have also indicated that adversive movements can be elicited through its repetitive electrical stimulation 1,~1. Finally, studies on Parkinsonism have stressed another possible aspect of its 'motor' function H. A separate approach to this problem might consist of analyzing changes in the firing rate of caudate units prior to or during the performance o f a given, stereotyped forelimb movement. This method has been successfully applied in monkeys, for studying the participation of other structures like the pyramidal tract 9, pallidum 6 and cerebellum 22 in hand movements. It was also applied recently to the putamen by the same group 7. Our studies on this subject began in 1969 and were pursued until now; they were performed with essentially the same methodology as other groups, except that the types of movement to which the animal was trained were somewhat different. In order to save space, no detailed description of the methodology will be given here. About 20 monkeys (Macaca nemestrina) were employed; the animals were implanted with an adequate system for unit recording and another one for rigid fixation of the skull. The monkeys were trained to perform a given movement; the type of movement was varied in the course of these experiments. (1) In a first group (I) the animals were to perform a somewhat complex prehension movement with a given hand, consisting in picking up solid food out of a hole carved in a food tray. The tray appeared from behind a board and was pushed forward by the operator. No specific go-signal was used in this paradigm, except that movements and noise made by the operator just before pushing the tray could eventually be a signal for the animal.
CAUDATE UNIT ACTIVATIONS DURING MOVEMENT
339
(2) It was later on considered that picking up food was too complex. Simple movements were consequently sought by using a conventional liquid feeder with a solenoid operated valve. (2a) In a first series of animals, the monkey was trained to press a lever, thus using essentially its distal joints. The lever was retractable and only presented to the animal after delivery of a go-signal. This program will be called hereafter (II). (2b) In a second series (program III), the movement to be performed was an adduction of the forearm and the arm, i.e., mainly of proximal joints: the animal had to pull on a string attached to its wrist, so lifting a given weight, and finally received food at the end of the (quasi-isotonic) movement. In all 3 experimental conditions, the following parameters were recorded: (a) unit activity in the caudate (steel or tungsten microelectrodes); (b) E M G activity from adequate muscles (triceps or biceps brachii in I; finger extensors on dorsal forearm in II; biceps and/or triceps in III); (c) adequate signals, like go-signal when employed, operation of the solenoid valve, etc. Concerning muscle recordings, a choice was made after preliminary multiple EMG test sessions had been performed in order to select as best as possible the first group of active muscles in each case. The aim of using such varied types of movements is clear: having first employed a very complex movement (arm and forearm extension toward food-well, finger prehension followed by arm and forearm flexion toward mouth and finally chewing), our concern was to somewhat simplify the experimental conditions, using either a dominant-distal movement or a dominant-proximal one. In fact, with lever pressing, the movement was mainly, but not exclusively, performed with hand and wrist; on the other hand, with arm traction, practically no participation of the fingers could be noticed. In all 3 experimental conditions, the non-active arm was held so as to prohibit extraneous movements. All parameters, signals, and bioelectric activities were recorded on tape. They were then displayed after the unit activities had been fed into a frequency-to-voltage converter, on a Brush rectilinear ink writer. In cases II and III the data were usually further processed in various classical ways (sequential spike density histograms; raster displays; averaging of the frequency analogue curve etc.). When averages or histograms were computed (in programs II and III), a forward and backward evaluation was performed using the movement as a time reference and thus displaying a control period of at least 3 sec prior to the movement. After 2-3 months, the animals were anesthetized, perfused with formalin, and their brain frozen sectioned and Nissl stained. The electrode tracks could usually not be followed with precision. However, the trace left by the upper part of the electrode, consisting in a large diameter guide, could usually be found on the slides; the actual depth of each electrode was then calculated from the micrometer reading during recording, thus using the anatomical position of the guide as a reference. Two categories of data will be described : first, units will be considered whose firing was altered in correlation with the movement; secondly, we shall briefly mention other patterns of cell discharges observed during the course of these experiments,
340
P. BUSER
Program
Total no. of cells
No. of cells" modified
1 (complex 11 (distal) Ili (proximal)
210 90 163
68 (30%) 39 (40%) 26 (15 %)
which seemed n o t directly related to the m o v e m e n t itself yet more likely to the exp e r i m e n t a l conditions.
(1) Caudate units modifying discharges in relation to the movement (Fig. 1, M I, M lI, M I I I ) . Our m a i n findings can be summarized as follows. (a) I n all 3 experimental conditions, units could be f o u n d which were localized within the head of the caudate nucleus a n d displayed alterations o f their firing pattern in correlation with the m o t o r task, as seen in the table above. (b) A l t h o u g h the total n u m b e r of recorded cells was limited, it seems that the p r o p o r t i o n o f movement-correlated units was higher in the case of distal than of proximal movements. (c) Movement-correlated cells could be f o u n d in all parts o f the head of the caudate nucleus, anterior a n d / o r posterior parts, and dorsal a n d / o r ventral ones. G i v e n the limited n u m b e r of active cells, n o specific localization has easily been revealed. Also, it has n o t been possible to lateralize the units with respect to the m o v e m e n t : units were either ipsilateral or contralateral to the active anterior limb. (d) The basic firing rate of most units always r e m a i n e d very low (10-20/sec, sometimes even lower). As a rule, r e s p o n d i n g cells increased their firing during
Fig. 1. Examples of caudate unit activations in various experimental conditions: M, during movement; S, to sensory stimulation; I, lI, III respectively, in test situations of program I, II, and III (see text). M la" unit displaying increased discharge frequency at start of tray movement. Within M Ia: A, unit discharge rate curve (after frequency to voltage conversion); notice calibration in imp./sec; B, EMG of triceps brachii muscle (notice calibration in mV); C, movement of tray (arrow up, appearance of tray and movement towards animal; arrow down, pull back); D, contact of hand on food-well. M lb: unit with increased discharge frequency during mastication. Within M lb: A, unit discharge rate; B, biceps brachii; C, masticatory muscles; D, movement of tray; E, contact of hand on food-well. MIII: unit with increased discharge during proximal pulling movement. Within M I l I : A, unit discharge rate; B, EMG of biceps-triceps brachii; C, photocell, signal of movement. M ll: computer processing of 19 successive trials in program II (distal hand movement). A given fixed delay after onset of the go-signal (light), the retractable lever was presented to the animal. Cell activity and EMG of finger extensor were recorded together with signals of light, of lever presentation and of lever pressing. All data were stored on tape. The computer analysis was performed (forward and backward) in relation to the time of lever pressing (vertical arrow below A). Within M II: A, averaging of lever pressing signal; B, averaged EMG of finger extensors; C, sequential impulse density function, with time intervals of 40 msec; D, average signal of lever presentation (out-in) and go-signal (on-off). Notice that the lever pressing occurred at variable delay after light onset and lever outlet. S I: unit showing no activation during manipulation of the animal's arm (at arrows below D) eliciting some reflex contraction. Strong activation during prehension movement. Within S I: A, unit; B, triceps brachii; C, movement of tray (see M Ia); D, arrows, passive manipulation of the arm; bar, contact of hand on food-well. S III: unit displaying a very slight acceleration during proximal movement, as indicated by EMG (program IIl, see text); on the other hand, intense activation following each of two intense brief sounds (metallic object against a table, at arrows). Within S Ill : A, conditioning signal; B, unit discharge rate; C, combined EMG of biceps and triceps.
341
CAUDATE UNIT ACTIVATIONS DURING MOVEMENT
movements; no silent cell, only activated by the movement, could be found. Very few (6 out of the total 133) displayed a decrease in their firing. Maximum increases in frequency were of about 30-100~. (e) All cells were not activated at the same stage of the movement. In program I, with the prehension movement lasting several seconds, certain distinctions could be made: 12 cells tended to fire in the very early phases of the movement; the majority of the units (n = 44) modified their activity during the prehension with fingers and flexion of the arm; other units increased their firing rate later on during chewing (n = 12). In program II, the distal wrist and hand movement being much more brief
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(more 'ballistic'16), the distinction of categories was more difficult; however, 7 cells showed a very early increase in their firing rate, whereas the rest of the active units changed during or just after completion of the forward movement. Some cells were even accelerated a few seconds following lever press. Finally, a certain dispersion of the peaks of activities with respect to movement was also noticed in paradigm II1 (proximal movement), although no 'very early' activation was noticed. (f) This problem of very early activation of cells remains precisely unsolved. In programs I and II (but not in Ill) cells were observed which proved to be activated in the very early stages of motor performance or even prior to movement as confirmed by the E M G (in case I). It has not yet been possible to determine whether such cells accompanied an unidentified muscle contraction occurring very early and not recorded in the EMG, or if their activation was in some way related to the 'decision making' process following the early signal announcing food. The problem thus posed is hardly solvable. That more complex and ill-identified conditions of excitation of caudate cells can exist, however, will be dealt with below. (2) Possible sensory activation of caudate cells. In the anesthetized cat preparation, it has long been known2, el that caudate cells can be activated through sensory stimulations of varied modalities (actually all 3 major ones, somatic, visual and acoustic, have revealed effective). Whether these projections reach the caudate through thalamo-striate projections (originating from some parts of the posteromedial thalamic nuclei (see ref. 19) like centralis lateralis) or through cortico-caudate pathways, anatomically and electrophysiologically well identified 3,12,1s,2°,23,z4, has not yet been settled. At any rate, it has also been shown that cortical projection areas can provide amplitude modulation of these caudate sensory responses s. Taken together, these facts raise the possibility of a sensory (rather than motor) origin of the observed caudate excitations described above (in possible correlation to cortical excitation). Three aspects of our observations regarding this problem shall be considered briefly (Fig. 1, S I, S 1II). (a) A first objection could be made that the observed activations were due to somatic (proprio- and/or exteroceptive) messages produced by the movement itself. The question thus formulated is not easily solvable as no criterion based upon latencies alone could be employed due to the failure of most of the accelerations of firing to anticipate movement. It was observed moreover that on many occasions a passive mobilization of the limb did not activate a cell just previously accelerated during the voluntary movement. Therefore, it seems rather unlikely that this somatic reafference was responsible for the observed correlations. (b) At first, we thought that the go-signal would by itself activate the caudate units because of its signification to the subject. This of course would have permitted us to conclude that caudate acceleration starts soon after the 'conditioned' signal and is prolonged approximately until the completion of the movement. This, however, could not be proved in this stage of our experiments. (c) Afterwards, we searched for more sophisticated types of sensory activations. Earlier in these experiments 14, some caudate cells had been found whose behavior was puzzling, being activated by the sight of fruit but not by that of an insignificant
CAUDATE UNIT ACTIVATIONS DURING MOVEMENT
343
stimulus (for the animal). We have more recently been searching for such units systematically, during the sessions with movements, and testing the cells in the intertrial periods. Many cells were thus encountered which did not alter their firing during the movement itself, nor when the go-signal was applied (such cells were neglected before, being unresponsive to movement) but which were strongly activated when some object was presented to the animal or some noise was made. It is for the time being impossible to stretch further this description of efficient 'monkey stimuli'; their category has been revealed extremely difficult to characterize (that they belong to categories as 'strange' or 'novel' or 'significant' has not been ascertained). The only common feature (which is still subjective observation) is that all did attract the animal's attention. Ultimately, our problem was to determine whether a possible source of artefact could be eye movements, which would accompany (or produce) firing of these so-called 'attention cells'. No systematic recording of eye movements has actually been performed yet. However, absolutely no correlation could be found between fixation saccades of the animal as observed by the operator and these cell accelerations. This research was supported by grants from the following institutions: Enseignement sup6rieur; C.N.R.S. (E.R.A. No. 411); I.N.S.E.R.M. (Contrat No. 71.1164); Fondation pour la Recherche m6dicale fran9aise.
1 AKERT, K., UND ANDERSSON,B., Experimenteller Beitrag zur Physiologie des Nucleus caudatus, Aeta physiol, scand., 22 (1951) 281-298. 2 ALBE-FESSARD, D., ROCHA-MIRANDA,C., ET OSWALDO-CRuz, E., Activit6s 6voqu6es dans le noyau caud6 du chat en r6ponse ~ divers types d'aff6rences. II. Etude microphysiologique, Electroenceph, clin. Neurophysiol., 12 (1960) 649-661. 3 BUCHWALD,N. A., HULL, C. n., VERNON, L. i . , AND BERNARDI,G. A., Physiological and psychological aspects of basal ganglia functions. In G. CRANEAND R. GARDNER(Eds.), Psychotropic Drugs and Dysfunctions of the Basal Ganglia, PHS Publications, US Gvt Printing Office, Washington, D.C. 1969, pp. 92-97. 4 BUCHWALD, N.A., WYERS, E.J., LAUPRECHT, C. W., AND HEUSER, G., The 'caudate-spindle'. IV. A behavioral index of caudate-induced inhibition, Electroenceph. clin. Neurophysiol., 13 (1961) 521-537. 5 BUSER,P., ROUGEUL,A., AND PERRET,C., Caudate and thalamic influences on conditioned motor responses in the cat, Bol. Inst. Estud. todd. biol. (Mdx.), 22 (1964) 293-307. 6 DELONG, M. R., Activity of basal ganglia neurons during movement, Brain Research, 40 (1972) 127-135. 7 DELONG, M . R . , Putamen: Activity of single units during slow and rapid arm movements, Science, 179 (1973) 1040-1042. 8 ENCABO,H., ET BUSER, P., Influence des aires primaires n6ocorticales sur les r6ponses sensorielles visuelles et acoustiques de la t6te du noyau caud6, Electroenceph. clin. Neurophysiol., 17 (1964) 144-153. 9 EVARTS, E. D., Pyramidal tract activity associated with a conditioned hand movement in the monkey, J. Neurophysiol., 29 (1966) 1011-1027. 10 Fox, S. S., AND O'BRmN, J. H., Inhibition and facilitation of afferent information by the caudate nucleus, Science, 137 (1962) 423--425. 11 JUNG, R., ANO HASSLER,R., The extrapyramidal motor system. In J. FIELD, H. W. MAGOUNAND V. E. HALL (Eds.), Handbook of Physiology, Sect. I, Neurophysiology, Vol. 2, Amer. Physiol. Soc., Washington, D. C., 1960, pp. 863-928. 12 KEMP, J. M., AND POWELL, T. P. S., The cortico-striate projection in the monkey, Brain, 93 (1970) 525-546.
344
P. I~US~R
13 KITSIKIS, A., The suppression of arm movements in monkey: threshold variations of caudate nucleus stimulation, Brain Research, 10 (1968) 460-462. 14 KITSIKIS,A., ANGY.kN, L., AND BUSER, P., Basal ganglia unitary activity during a motor performance in monkeys, Physiol. Behav., 6 (1971) 609-611. 15 KITSIKIS,A., AND ROUGEUL,A., The effect of caudate stimulation on conditioned motor behavior in monkey, Physiol. Behav., 3 (1968) 831-837. 16 KORNHOBER,H. H., Motor functions of cerebellum and basal ganglia: The cerebellocortical saccadic (ballistic) clock, the cerebellonuclear hold regulator, and the basal ganglia ramp (voluntary speed smooth movement)generator, Kybernetik, 8 (1971) 157-162. 17 KRAUTHAMER,G., AND ALBE-FESSARD,D., Inhibition of non-specific sensory activities following striopallidal and capsular stimulation, J. Neurophysiol., 28 (1965) 100-124. 18 NAUTA, W. J. H., Some efferent connections of the prefrontal cortex in the monkey. In J. M. WARREN AND K. AKERT (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, New York, 1964, pp. 397409. 19 PURPURA, D. P., ANn MALLIANI, A., Intracellular studies of the corpus striatum. I. Synaptic potentials and discharge characteristics of caudate neurons activated by thalamic stimulation, Brain Research, 6 (1967) 325-340. 20 ROCHA-MIRANDA,C. E., Single-unit analysis of cortex-caudate connections, Electroenceph. clin. Neurophysiol., 19 (1965) 237-247. 21 SEDGWICK, E. M., AND WILLIAMS, T. D., The response of single units in the caudate nucleus to peripheral stimulation, J. Physiol. (Lond.), 189 (1967) 281-298. 22 THACH, W. T., Discharge of Purkinje and cerebellar nuclear neurons during rapidly alternating arm movements in the monkey, J. Neurophysiol., 31 (1968) 785-798. 23 WALL, P. D., GLEES, P., AND FULTON, J. F., Corticofugal connexions of posterior orbital surface in rhesus monkey, Brain, 74 (1951) 66-71. 24 WHITLOCK, D. G., AND NAUTA, W. J. H., Subcortical projections from the temporal neocortex in Macaca mulatta, J. comp. NeuroL, 106 (1956) 183-212.
337
Colloque C.N.R.S. no. 226 Comportement moteur et activit6s nerveuses programm6es Aix-en-Provence, 7-9 sept. 1973
S I N G L E U N I T R E C O R D I N G 1N T H E C A U D A T E N U C L E U S D U R I N G SESSIONS W I T H E L A B O R A T E MOVEMENTS IN T H E A W A K E M O N K E Y
PIERRE BUSER*, G. P O U D E R O U X AND J. M E R E A U X
Laboratoire de Neurophysiologie comparde, Universitd Paris VI, 75230 Paris Cddex 05 (France)
SUMMARY
Unit recordings were performed in the caudate nucleus o f awake macaques. Animals were maintained in a restraining chair and had been trained to perform various types o f elaborate movements to obtain food-reward. Three types of movement were studied: (a) natural, large gestures of grasping solid food (peanut) from a tray and bringing it to the mouth; (b) small amplitude lever-pressing movements for fluid reward (fruit juice), mainly involving distal segments (fingers, wrist); (c) same as (b), but involving essentially proximal musculature, and consisting o f an ample isotonic pulling with arm and shoulder. Units were recorded before and during each of the preceding types of movements (but in different animals). Results indicate that: (1) caudate cells were encountered in all 3 cases which were accelerated during different stages o f the movement; (2) more cells were activated in situations (a) and (b) than (c); (3) very few cells displayed inhibition instead of excitation; (4) among cells modified during movement, very few were also accelerated through passive flexions or extensions of the forelimb; (5) some caudate cells were also clearly activated through various visual or auditory intercurrent stimuli, probably arousing the animal's attention.
RI~SUM~
On a effectu6 des d6rivations unitaires dans le noyau caud6 de macaques ~veill~s et conscients, maintenus en chaise, et dress6s A effectuer un mouvement du membre * Also with previous collaboration of Drs. A. Kitsikis, L. Angyan, T. Wishart and B. Faucheux.
338
P. BUSER
ant6rieur pour obtenir de la nourriture. Trois types de mouvements ont 6t6 adopt6s: (a) saisir un aliment solide (cacahou6te) sur un plateau, puis le porter/l sa bouche (geste ample et complexe); (b) appuyer sur un levier, d'un mouvement limit6, int6ressant essentiellement les extr6mit6s distales (doigts et poignet) pour d6clencher un distributeur de liquide; (c) effectuer une traction, principalement h I'aide des segments proximaux, 6galement pour actionner le distributeur de liquide. Des unit6s ont pu &re recueillies au cours de ces 3 types d'op6rations motrices. Les r6sultats se r6sument ainsi: (1) dans les 3 situations exp6rimentales des cellules caud6es ont 6t6 isol6es, qui 6taient acc616r6es pendant le mouvement; (2) le nombre de cellules activ6es s'est r6v616 plus abondant dans les situations (a) et (b) que dans la situation (c); (3) tr6s peu de cellules ont t6moign6 d'une inhibition (au lieu d'une excitation); (4) parmi les cellules modifi6es pendant le mouvement actif, tr6s peu furent 6galement activ6es par une mobilisation passive du membre ant6rieur correspondant: (5) certaines cellules caud6es ont r6pondu - - en l'absence de mouvement - - / i des stimulus intercurrents visuels ou acoustiques, probablement susceptibles d'6veiller l'attention de l'animal.
The participation of the caudate nucleus in motor elaboration remains a matter of discussion and controversy. A considerable number o f studies based upon behavioral4, 5,1a,1~ or electrophysiologicaP °,~7 observations have suggested that it exerts an 'inhibitory' action; some authors have also indicated that adversive movements can be elicited through its repetitive electrical stimulation 1,~1. Finally, studies on Parkinsonism have stressed another possible aspect of its 'motor' function H. A separate approach to this problem might consist of analyzing changes in the firing rate of caudate units prior to or during the performance o f a given, stereotyped forelimb movement. This method has been successfully applied in monkeys, for studying the participation of other structures like the pyramidal tract 9, pallidum 6 and cerebellum 22 in hand movements. It was also applied recently to the putamen by the same group 7. Our studies on this subject began in 1969 and were pursued until now; they were performed with essentially the same methodology as other groups, except that the types of movement to which the animal was trained were somewhat different. In order to save space, no detailed description of the methodology will be given here. About 20 monkeys (Macaca nemestrina) were employed; the animals were implanted with an adequate system for unit recording and another one for rigid fixation of the skull. The monkeys were trained to perform a given movement; the type of movement was varied in the course of these experiments. (1) In a first group (I) the animals were to perform a somewhat complex prehension movement with a given hand, consisting in picking up solid food out of a hole carved in a food tray. The tray appeared from behind a board and was pushed forward by the operator. No specific go-signal was used in this paradigm, except that movements and noise made by the operator just before pushing the tray could eventually be a signal for the animal.
CAUDATE UNIT ACTIVATIONS DURING MOVEMENT
339
(2) It was later on considered that picking up food was too complex. Simple movements were consequently sought by using a conventional liquid feeder with a solenoid operated valve. (2a) In a first series of animals, the monkey was trained to press a lever, thus using essentially its distal joints. The lever was retractable and only presented to the animal after delivery of a go-signal. This program will be called hereafter (II). (2b) In a second series (program III), the movement to be performed was an adduction of the forearm and the arm, i.e., mainly of proximal joints: the animal had to pull on a string attached to its wrist, so lifting a given weight, and finally received food at the end of the (quasi-isotonic) movement. In all 3 experimental conditions, the following parameters were recorded: (a) unit activity in the caudate (steel or tungsten microelectrodes); (b) E M G activity from adequate muscles (triceps or biceps brachii in I; finger extensors on dorsal forearm in II; biceps and/or triceps in III); (c) adequate signals, like go-signal when employed, operation of the solenoid valve, etc. Concerning muscle recordings, a choice was made after preliminary multiple EMG test sessions had been performed in order to select as best as possible the first group of active muscles in each case. The aim of using such varied types of movements is clear: having first employed a very complex movement (arm and forearm extension toward food-well, finger prehension followed by arm and forearm flexion toward mouth and finally chewing), our concern was to somewhat simplify the experimental conditions, using either a dominant-distal movement or a dominant-proximal one. In fact, with lever pressing, the movement was mainly, but not exclusively, performed with hand and wrist; on the other hand, with arm traction, practically no participation of the fingers could be noticed. In all 3 experimental conditions, the non-active arm was held so as to prohibit extraneous movements. All parameters, signals, and bioelectric activities were recorded on tape. They were then displayed after the unit activities had been fed into a frequency-to-voltage converter, on a Brush rectilinear ink writer. In cases II and III the data were usually further processed in various classical ways (sequential spike density histograms; raster displays; averaging of the frequency analogue curve etc.). When averages or histograms were computed (in programs II and III), a forward and backward evaluation was performed using the movement as a time reference and thus displaying a control period of at least 3 sec prior to the movement. After 2-3 months, the animals were anesthetized, perfused with formalin, and their brain frozen sectioned and Nissl stained. The electrode tracks could usually not be followed with precision. However, the trace left by the upper part of the electrode, consisting in a large diameter guide, could usually be found on the slides; the actual depth of each electrode was then calculated from the micrometer reading during recording, thus using the anatomical position of the guide as a reference. Two categories of data will be described : first, units will be considered whose firing was altered in correlation with the movement; secondly, we shall briefly mention other patterns of cell discharges observed during the course of these experiments,
340
P. BUSER
Program
Total no. of cells
No. of cells" modified
1 (complex 11 (distal) Ili (proximal)
210 90 163
68 (30%) 39 (40%) 26 (15 %)
which seemed n o t directly related to the m o v e m e n t itself yet more likely to the exp e r i m e n t a l conditions.
(1) Caudate units modifying discharges in relation to the movement (Fig. 1, M I, M lI, M I I I ) . Our m a i n findings can be summarized as follows. (a) I n all 3 experimental conditions, units could be f o u n d which were localized within the head of the caudate nucleus a n d displayed alterations o f their firing pattern in correlation with the m o t o r task, as seen in the table above. (b) A l t h o u g h the total n u m b e r of recorded cells was limited, it seems that the p r o p o r t i o n o f movement-correlated units was higher in the case of distal than of proximal movements. (c) Movement-correlated cells could be f o u n d in all parts o f the head of the caudate nucleus, anterior a n d / o r posterior parts, and dorsal a n d / o r ventral ones. G i v e n the limited n u m b e r of active cells, n o specific localization has easily been revealed. Also, it has n o t been possible to lateralize the units with respect to the m o v e m e n t : units were either ipsilateral or contralateral to the active anterior limb. (d) The basic firing rate of most units always r e m a i n e d very low (10-20/sec, sometimes even lower). As a rule, r e s p o n d i n g cells increased their firing during
Fig. 1. Examples of caudate unit activations in various experimental conditions: M, during movement; S, to sensory stimulation; I, lI, III respectively, in test situations of program I, II, and III (see text). M la" unit displaying increased discharge frequency at start of tray movement. Within M Ia: A, unit discharge rate curve (after frequency to voltage conversion); notice calibration in imp./sec; B, EMG of triceps brachii muscle (notice calibration in mV); C, movement of tray (arrow up, appearance of tray and movement towards animal; arrow down, pull back); D, contact of hand on food-well. M lb: unit with increased discharge frequency during mastication. Within M lb: A, unit discharge rate; B, biceps brachii; C, masticatory muscles; D, movement of tray; E, contact of hand on food-well. MIII: unit with increased discharge during proximal pulling movement. Within M I l I : A, unit discharge rate; B, EMG of biceps-triceps brachii; C, photocell, signal of movement. M ll: computer processing of 19 successive trials in program II (distal hand movement). A given fixed delay after onset of the go-signal (light), the retractable lever was presented to the animal. Cell activity and EMG of finger extensor were recorded together with signals of light, of lever presentation and of lever pressing. All data were stored on tape. The computer analysis was performed (forward and backward) in relation to the time of lever pressing (vertical arrow below A). Within M II: A, averaging of lever pressing signal; B, averaged EMG of finger extensors; C, sequential impulse density function, with time intervals of 40 msec; D, average signal of lever presentation (out-in) and go-signal (on-off). Notice that the lever pressing occurred at variable delay after light onset and lever outlet. S I: unit showing no activation during manipulation of the animal's arm (at arrows below D) eliciting some reflex contraction. Strong activation during prehension movement. Within S I: A, unit; B, triceps brachii; C, movement of tray (see M Ia); D, arrows, passive manipulation of the arm; bar, contact of hand on food-well. S III: unit displaying a very slight acceleration during proximal movement, as indicated by EMG (program IIl, see text); on the other hand, intense activation following each of two intense brief sounds (metallic object against a table, at arrows). Within S Ill : A, conditioning signal; B, unit discharge rate; C, combined EMG of biceps and triceps.
341
CAUDATE UNIT ACTIVATIONS DURING MOVEMENT
movements; no silent cell, only activated by the movement, could be found. Very few (6 out of the total 133) displayed a decrease in their firing. Maximum increases in frequency were of about 30-100~. (e) All cells were not activated at the same stage of the movement. In program I, with the prehension movement lasting several seconds, certain distinctions could be made: 12 cells tended to fire in the very early phases of the movement; the majority of the units (n = 44) modified their activity during the prehension with fingers and flexion of the arm; other units increased their firing rate later on during chewing (n = 12). In program II, the distal wrist and hand movement being much more brief
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(more 'ballistic'16), the distinction of categories was more difficult; however, 7 cells showed a very early increase in their firing rate, whereas the rest of the active units changed during or just after completion of the forward movement. Some cells were even accelerated a few seconds following lever press. Finally, a certain dispersion of the peaks of activities with respect to movement was also noticed in paradigm II1 (proximal movement), although no 'very early' activation was noticed. (f) This problem of very early activation of cells remains precisely unsolved. In programs I and II (but not in Ill) cells were observed which proved to be activated in the very early stages of motor performance or even prior to movement as confirmed by the E M G (in case I). It has not yet been possible to determine whether such cells accompanied an unidentified muscle contraction occurring very early and not recorded in the EMG, or if their activation was in some way related to the 'decision making' process following the early signal announcing food. The problem thus posed is hardly solvable. That more complex and ill-identified conditions of excitation of caudate cells can exist, however, will be dealt with below. (2) Possible sensory activation of caudate cells. In the anesthetized cat preparation, it has long been known2, el that caudate cells can be activated through sensory stimulations of varied modalities (actually all 3 major ones, somatic, visual and acoustic, have revealed effective). Whether these projections reach the caudate through thalamo-striate projections (originating from some parts of the posteromedial thalamic nuclei (see ref. 19) like centralis lateralis) or through cortico-caudate pathways, anatomically and electrophysiologically well identified 3,12,1s,2°,23,z4, has not yet been settled. At any rate, it has also been shown that cortical projection areas can provide amplitude modulation of these caudate sensory responses s. Taken together, these facts raise the possibility of a sensory (rather than motor) origin of the observed caudate excitations described above (in possible correlation to cortical excitation). Three aspects of our observations regarding this problem shall be considered briefly (Fig. 1, S I, S 1II). (a) A first objection could be made that the observed activations were due to somatic (proprio- and/or exteroceptive) messages produced by the movement itself. The question thus formulated is not easily solvable as no criterion based upon latencies alone could be employed due to the failure of most of the accelerations of firing to anticipate movement. It was observed moreover that on many occasions a passive mobilization of the limb did not activate a cell just previously accelerated during the voluntary movement. Therefore, it seems rather unlikely that this somatic reafference was responsible for the observed correlations. (b) At first, we thought that the go-signal would by itself activate the caudate units because of its signification to the subject. This of course would have permitted us to conclude that caudate acceleration starts soon after the 'conditioned' signal and is prolonged approximately until the completion of the movement. This, however, could not be proved in this stage of our experiments. (c) Afterwards, we searched for more sophisticated types of sensory activations. Earlier in these experiments 14, some caudate cells had been found whose behavior was puzzling, being activated by the sight of fruit but not by that of an insignificant
CAUDATE UNIT ACTIVATIONS DURING MOVEMENT
343
stimulus (for the animal). We have more recently been searching for such units systematically, during the sessions with movements, and testing the cells in the intertrial periods. Many cells were thus encountered which did not alter their firing during the movement itself, nor when the go-signal was applied (such cells were neglected before, being unresponsive to movement) but which were strongly activated when some object was presented to the animal or some noise was made. It is for the time being impossible to stretch further this description of efficient 'monkey stimuli'; their category has been revealed extremely difficult to characterize (that they belong to categories as 'strange' or 'novel' or 'significant' has not been ascertained). The only common feature (which is still subjective observation) is that all did attract the animal's attention. Ultimately, our problem was to determine whether a possible source of artefact could be eye movements, which would accompany (or produce) firing of these so-called 'attention cells'. No systematic recording of eye movements has actually been performed yet. However, absolutely no correlation could be found between fixation saccades of the animal as observed by the operator and these cell accelerations. This research was supported by grants from the following institutions: Enseignement sup6rieur; C.N.R.S. (E.R.A. No. 411); I.N.S.E.R.M. (Contrat No. 71.1164); Fondation pour la Recherche m6dicale fran9aise.
1 AKERT, K., UND ANDERSSON,B., Experimenteller Beitrag zur Physiologie des Nucleus caudatus, Aeta physiol, scand., 22 (1951) 281-298. 2 ALBE-FESSARD, D., ROCHA-MIRANDA,C., ET OSWALDO-CRuz, E., Activit6s 6voqu6es dans le noyau caud6 du chat en r6ponse ~ divers types d'aff6rences. II. Etude microphysiologique, Electroenceph, clin. Neurophysiol., 12 (1960) 649-661. 3 BUCHWALD,N. A., HULL, C. n., VERNON, L. i . , AND BERNARDI,G. A., Physiological and psychological aspects of basal ganglia functions. In G. CRANEAND R. GARDNER(Eds.), Psychotropic Drugs and Dysfunctions of the Basal Ganglia, PHS Publications, US Gvt Printing Office, Washington, D.C. 1969, pp. 92-97. 4 BUCHWALD, N.A., WYERS, E.J., LAUPRECHT, C. W., AND HEUSER, G., The 'caudate-spindle'. IV. A behavioral index of caudate-induced inhibition, Electroenceph. clin. Neurophysiol., 13 (1961) 521-537. 5 BUSER,P., ROUGEUL,A., AND PERRET,C., Caudate and thalamic influences on conditioned motor responses in the cat, Bol. Inst. Estud. todd. biol. (Mdx.), 22 (1964) 293-307. 6 DELONG, M. R., Activity of basal ganglia neurons during movement, Brain Research, 40 (1972) 127-135. 7 DELONG, M . R . , Putamen: Activity of single units during slow and rapid arm movements, Science, 179 (1973) 1040-1042. 8 ENCABO,H., ET BUSER, P., Influence des aires primaires n6ocorticales sur les r6ponses sensorielles visuelles et acoustiques de la t6te du noyau caud6, Electroenceph. clin. Neurophysiol., 17 (1964) 144-153. 9 EVARTS, E. D., Pyramidal tract activity associated with a conditioned hand movement in the monkey, J. Neurophysiol., 29 (1966) 1011-1027. 10 Fox, S. S., AND O'BRmN, J. H., Inhibition and facilitation of afferent information by the caudate nucleus, Science, 137 (1962) 423--425. 11 JUNG, R., ANO HASSLER,R., The extrapyramidal motor system. In J. FIELD, H. W. MAGOUNAND V. E. HALL (Eds.), Handbook of Physiology, Sect. I, Neurophysiology, Vol. 2, Amer. Physiol. Soc., Washington, D. C., 1960, pp. 863-928. 12 KEMP, J. M., AND POWELL, T. P. S., The cortico-striate projection in the monkey, Brain, 93 (1970) 525-546.
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13 KITSIKIS, A., The suppression of arm movements in monkey: threshold variations of caudate nucleus stimulation, Brain Research, 10 (1968) 460-462. 14 KITSIKIS,A., ANGY.kN, L., AND BUSER, P., Basal ganglia unitary activity during a motor performance in monkeys, Physiol. Behav., 6 (1971) 609-611. 15 KITSIKIS,A., AND ROUGEUL,A., The effect of caudate stimulation on conditioned motor behavior in monkey, Physiol. Behav., 3 (1968) 831-837. 16 KORNHOBER,H. H., Motor functions of cerebellum and basal ganglia: The cerebellocortical saccadic (ballistic) clock, the cerebellonuclear hold regulator, and the basal ganglia ramp (voluntary speed smooth movement)generator, Kybernetik, 8 (1971) 157-162. 17 KRAUTHAMER,G., AND ALBE-FESSARD,D., Inhibition of non-specific sensory activities following striopallidal and capsular stimulation, J. Neurophysiol., 28 (1965) 100-124. 18 NAUTA, W. J. H., Some efferent connections of the prefrontal cortex in the monkey. In J. M. WARREN AND K. AKERT (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, New York, 1964, pp. 397409. 19 PURPURA, D. P., ANn MALLIANI, A., Intracellular studies of the corpus striatum. I. Synaptic potentials and discharge characteristics of caudate neurons activated by thalamic stimulation, Brain Research, 6 (1967) 325-340. 20 ROCHA-MIRANDA,C. E., Single-unit analysis of cortex-caudate connections, Electroenceph. clin. Neurophysiol., 19 (1965) 237-247. 21 SEDGWICK, E. M., AND WILLIAMS, T. D., The response of single units in the caudate nucleus to peripheral stimulation, J. Physiol. (Lond.), 189 (1967) 281-298. 22 THACH, W. T., Discharge of Purkinje and cerebellar nuclear neurons during rapidly alternating arm movements in the monkey, J. Neurophysiol., 31 (1968) 785-798. 23 WALL, P. D., GLEES, P., AND FULTON, J. F., Corticofugal connexions of posterior orbital surface in rhesus monkey, Brain, 74 (1951) 66-71. 24 WHITLOCK, D. G., AND NAUTA, W. J. H., Subcortical projections from the temporal neocortex in Macaca mulatta, J. comp. NeuroL, 106 (1956) 183-212.