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Properties of visual cue responses in primate precentral cortex
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24
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Elsc~icl BRE 10988
Properties of Visual Cue Responses in Primate Precentral Cortex H. C. KWAN, W. A. MACKAY, J. T. MURPHY and Y. C. WONG
Department of Physiology, University of Toronto, Toronto, Ont. M5S 1A8 (Canada) (Accepted December llth, 1984)
Key words: precentral neuron - - visual stimulus - - monkey
Monkeys were trained to perform a visuomotor task involving the alignment of a cursor over a vertical target line on a videomonitor by flexion or extension movements of the wrist. The forelimb area of the contralateral precentral cortex was thoroughly explored during the task. Intracortical microstimulation was employed to classify the forelimb region into wrist flexion-extension and non-wrist flexion-extension populations. Unit recording revealed an initial response to the cue for movement, viz. the appearance of the cursor and target line on the videomonitor, while visual signals not related to the task failed to evoke any response. The mean latencyof these visual cue responses was approximately 150 ms, A great majority of the responses (96%) were bidirectional in character, in that they did not correlate with the directional information embedded in the visual cue, nor were they good predictors for the direction or timing of the subsequent movement. They were uniformly distributed in both the wrist and non-wrist regions of the forelimb area: the nonforelimb areas were devoid of the cue response. Further, when the variability of response to the visual cue for the wrist and non-wrist populations was compared, no significant difference was observed. These observations are consistent with an interpretation that the visually triggered cue responses provide a generalized activation over the task-related area of precentral cortex, paving the way for later and more specific activations leading to the execution of the task.
INTRODUCTION
In a r e c e n t series of e x p e r i m e n t s t6,23,29,30, we studied n e u r o n a l b e h a v i o r in p r e c e n t r a l c o r t e x in differ-
N u m e r o u s studies h a v e b e e n u n d e r t a k e n to e x a m ine the b e h a v i o r of n e u r o n s in the p r e c e n t r a t m o t o r c o r t e x d u r i n g a v i s u o m o t o r task4,5,7-1k13,14,17,21-23, 25.
ent phases of a v i s u o m o t o r task. w h i c h i n c l u d e d the initial p r e s e n t a t i o n of a cue for wrist flexion o r e x t e n sion m o v e m e n t , f o l l o w e d l a t e r by a visual o r s o m a t i c
26,30,31. A g e n e r a l c o n c l u s i o n e m e r g i n g f r o m t h e s e
' p e r t u r b a t i o n ' . In this r e p o r t , w e e x a m i n e the extent
studies is that the n a t u r e of the n e u r o n a l r e s p o n s e is
to which c o n t e x t - d e p e n d e n c e dictates b o t h t h e spa-
highly d e p e n d e n t on the n e u r o n a l t y p e f r o m which
tial and t e m p o r a l b e h a v i o r s of n e u r o n a l r e s p o n s e s
r e c o r d i n g s are m a d e and on t h e c o n t e x t in which the
triggered by the p r e s e n t a t i o n of a cue for m o v e m e n t
animal e x e c u t e s the v o l u n t a r y m o v e m e n t . F o r in-
in a task i n v o l v i n g flexion a n d e x t e n s i o n a b o u t the
stance, in o n e study 4 it was o b s e r v e d that p y r a m i d a l
'wrist. In particular, we c o m p a r e the p r o p e r t i e s o f a
tract n e u r o n s r e s p o n d e d to p h o t i c s t i m u l a t i o n if and
n e u r o n a l p o p u l a t i o n p u t a t i v e l y i d e n t i f i e d by intra-
only if the stimulus elicited a specific m o t o r r e s p o n s e .
cortical m i c r o s t i m u l a t i o n l , 15 as c o n t r o l l i n g wrist flex-
H o w e v e r , u n d e r a d i f f e r e n t set of e x p e r i m e n t a l cir-
ion or e x t e n s i o n m o v e m e n t with t h o s e of a n o t h e r
cumstances, m o d i f i c a t i o n of the cortical n e u r o n a l activity could be o b s e r v e d w i t h o u t any s u b s e q u e n t
p o p u l a t i o n which c o n t r o l s all o t h e r j o m t m o v e m e n t s of the f o r e l i m b .
m o d i f i c a t i o n of E M G 25. T h e s e o b s e r v a t i o n s highlight
A short c o m m u n i c a t i o n has b e e n published16,
the c o n t e x t - d e p e n d e n c e of p r e c e n t r a l n e u r o n a l responses to visual s t i m u l a t i o n , and p o i n t to the possi-
MATERIALS AND METHODS
bility that discharge of p r e c e n t r a l n e u r o n s m a y contribute to, but d o e s not necessarily l e a d to m o v e ment.
A d e t a i l e d d e s c r i p t i o n of the e x p e r i m e n t a l p a r a digm 20 has b e e n p r e s e n t e d previously. Briefly, two
Correspondence." H. C. Kwan, Department of Physiology. University of Toronto, Toronto, Ont. M5S 1A8. Canada. 0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
25 stump-tailed monkeys were trained to grasp a manipulandum connected to a torque motor. Flexion or extension of the wrist was translated into horizontal movement of a square cursor on a videomonitor which was placed 1 m from the animal. A vertical line, the position of which was computer controlled, was displayed on the monitor as well. The task of the monkey was to align the cursor over the vertical target line by means of either wrist flexion or extension movements. A fitted cast was placed around the forearm to minimize excessive movement of other joints than the wrist. The target line and cursor would then appear on the screen at random times. The appearance of the target line and cursor on the monitor, which constituted the cue for action, was then followed by alignment of the cursor over the target line. Under computer control this alignment was disturbed either by stepping the target line to the left or right of the cursor 23, or by a torque perturbation on the manipulandum which would dislodge the cursor from the target line 29. Successful realignment within a predetermined time period would lead to a juice or water reward. The present report will be concerned with the analysis of the precentral response during the initial phase of cue presentation.
was maintained below 3 k ~ to minimize m o v e m e n t artifact.
Classification of neurons A unit was classified as functionally related to a single joint by means of the criterion of intracortical microstimulation (ICMS) applied to the locus of recording 15. For instance, wrist extension (wrist-E) neurons were defined as those which, upon threshold ICMS at the recording locus, produced an extension movement about the wrist joint. The other class included shoulder, elbow, other-wrist (i.e. other than wrist flexion or extension), and finger neurons; this class was termed non-wrist (F-E) neurons. Wherever possible, the forelimb area was systematically explored in each monkey in order to reduce sampling bias for a certain region of the precentral cortex.
Histology Small electrolytic lesions were made at a number of recording sites upon completion of the series of experiments. Sixty-micron frozen serial sections were made and were later stained with cresyl violet. Recording loci were reconstructed on the basis of these electrolytic lesions, and in relation to cytoarchitectonic areas 4 and 6 28.
Data recording Upon completion of training, a burr hole was made in the skull over the precentral motor cortex and a stainless steel chamber was implanted under sterile conditions. The surgical methods for chronic recording have been fully described previously 28. Unit recordings from the precentral forelimb area were made over a period of 10 months. Glass-coated platinum-iridium microelectrodes with an average impedance of 0.5 MQ measured at 1 kHz were used. Units were discriminated in the conventional way using spike-height discrimination and sampled at 1 ms intervals. The displacement and velocity of the manipulandum were sampled at 10 ms intervals. In some recording sessions horizontal eye m o v e m e n t was monitored with surface disc E O G electrodes. During the initial phase of the experiments, E M G recording was performed to examine the patterns of discharge for the distal and proximal muscles participating in the task. Surface A g - A g C 1 electrodes (2 mm diameter) were used with an amplifier bandwidth of 50-1000 Hz. Electrode-to-skin impedance
Data analysis Data analysis, as detailed in our previous studies 23,29, was performed to detect differences in the response variability of the two populations of neurons in precentral cortex: wrist (F-E) and non-wrist (F-E) populations. The response of a neuron was defined as excitatory when the peristimulus time histogram (PSTH) showed two or more consecutive 10 ms bins, each containing a number of discharges exceeding two standard deviations (SD) about the mean number of discharges per bin in the prestimulus control period. In the case of inhibition, two sds below the mean control activity was employed as the criterion. Cells were then classified as task-related when modifications of discharge satisfied the above criteria. Two criteria were used to assess the variability of the response z3,29. First is the response index, P, which was defined as the ratio of responsive trials to the total number of trials. The second related to the variability of the timing of the onset of each response in single trials. The onset time of response in each
26 trial was defined by the onset time of the first spike in each response. These onset times were then used to / j'
compute the mean onset latencies with respect to the sensory event, Xs, and to the onset of the subsequent voluntary m o v e m e n t , X m , for all times. Correspond-
FLI ~Of
ing standard deviations, SD S and SD m, respectively, were also computed. x
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RESULTS
EMG patterns A sample of E M G activities from proximal and distal muscles during wrist flexion and extension movements is shown in Fig. 1. The wrist prime movers in general exhibited reciprocal patterns of activation, while others were organized in a reciprocal or bidirectional fashion. Both transient and sustained temporal activations could be observed (Fig. 1). The onset of E M G activity ranged from 20 to 150 ms before the onset of m o v e m e n t , and activation of proximal muscles tended to precede that of more distal ones.
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Fig. 1. Full-wave rectified and smoothed EMGof selected forelimb muscles during a single flexion and extension wrist movement. The uppermost traces show wrist angular displacement of 15° in the flexion direction on the left, and 15° extension 0n~ the right. Onset of wrist movement occurs at time0i The arrow marks the time of cue presentation. Vertical scales on the right indicate an EMG amplitude of 0.2 mV:
Analysis of reaction time The relative frequency histogram of reaction time for all the trials (n = 3350) is shown in Fig. 2. Here the reaction time was defined as the time when the velocity changes from its resting zero value. After the appearance of the cursor and the target line which constituted the cue, the mean reaction time was 259 ms ( + 71 ms). The range of the reaction times varied from 140 to 410 ms. In a small n u m b e r of trials (about
A
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: sd
2%) the reaction times were excessively prolonged (above 450 ms). These trials are not included in the present analysis.
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Temporal patterns of response Typical patterns of response to presentation of the visual cue are shown in Fig. 3. These patterns include phasic bursting responses as shown in A. those which exhibit a phasic c o m p o n e n t with a trailing tonic comp o n e n t as shown in D, and other intermediate patterns shown in B and C. Of the total 636 units identified somatotopically by means of ICMS, 279 units were found to be temporally correlated with the onset of the visual cue for movement. Of these. 90% showed excitatory responses while 10% showed inhibitory responses.
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V~ Fig. 2. Relative frequency histogram of reaction time. Vo, A: broken line indicates position of target line, and the solidline indicates cursor position and hence the hand position. The appearance of the cue occurs at the first arrow. The second arrow marks the time when the hand veloeity becomes.non-zero: this time is taken to be the reaction time. B: histogram of the reaction times, with mean latency, x, and standard deviation, sd. These abbreviations apply to all subsequent figures.Bin width is 10 ms. Horizontal axis: time after cue presentation (msl.
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Fig, 3. Patterns of the visual cue response. In A, the response of a unit to the cue is shown in raster form and in the corresponding peristimulus histogram. The arrow marks the appearance of the cue. This unit was identified as a shoulder flexion neuron (Sf) by [CMS. The numbers represent the mean latency for all the trials, with the standard deviation in parentheses, with respect to the sensor}' event, and the motor event (with negative mean latency). This convention applies to B which shows the response of an elbow flexion neuron (Ef), to C, which shows the response of an elbow extension neuron (Ee), and to D, which shows the response of a wrist flexion (Wf) neuron. Time scale: 500 ms per division. Bin width: 10 ms.
Relation to the visual cue and the direction o f move-
tions o v e r the e n t i r e f o r e l i m b a r e a (Fig. 9). A n e x a m -
ment A great m a j o r i t y ( 9 4 % ) of the units which re-
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s h o w e d two i n t e r e s t i n g f e a t u r e s . Firstly, t h e r e was in g e n e r a l a lack of c o r r e l a t i o n b e t w e e n these r e s p o n s e s and the d i r e c t i o n a l i n f o r m a t i o n c o n t a i n e d in the visual cue. S e c o n d l y , t h e r e was an a d d i t i o n a l lack of cor-
at this locus p r o d u c e d a wrist e x t e n s i o n m o v e m e n t , this unit re-
s p o n d e d to passive wrist flexion. Fig. 4B shows a non-wrist ( s h o u l d e r - e x t e n s i o n ) unit r e c o r d e d at a s e p a r a t e locus with a phasic plus
relation b e t w e e n the r e s p o n s e s and the d i r e c t i o n of
tonic p a t t e r n similar to that of Fig. 3D. In this set of trials, while the r e s p o n s e s to the cue w e r e f o l l o w e d
the s u b s e q u e n t m o v e m e n t , T h e s e r e s p o n s e s can be
by m o v e m e n t s of the wrist in e i t h e r d i r e c t i o n , these
d e s c r i b e d as bidirectional. T h e y w e r e o b s e r v e d in
m o v e m e n t s o c c u r r e d at v a r i a b l e times. As an e x a m -
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ple, in trial 4, t h e r e was a burst r e s p o n s e after cue
and n o n - w r i s t ( F - E )
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Fig. 4. Responses of two different precentral units to presentation of the visual cue. Solid traces indicate wrist position during a single trial, with upward direction representing extension, and downwards flexion. The action potentials are represented by short vertical lines immediately below. The criteria for response, based on prestimulus discharge statistics, are detailed in Methods. The triangle marks the time of cue presentation.
presentation, followed by a second burst which preceded the cessation of flexion m o v e m e n t . A n o t h e r example is found in trial 12. in which the cue response merged into a later and further increase in discharge, which was followed by an extension m o v e m e n t .
Context-dependent nature of the response The non-specific nature of the visually triggered cue response raises the possibility that these responses in the precentral cortex were merely startle responses and were not related to the task at hand. A n alternative possibility is that these responses were t e m p o r a l l y c o r r e l a t e d with the E O G rather than the sensory cue. To examine the first possibility, we used bright flashes of light in an effort to e v o k e responses in precentral neurons. These efforts proved to be futile. In o t h e r e x p e r i m e n t s , we p r e s e n t e d 'un-
familiar' visual patterns to the m o n k e y on t h e video monitor, i.e. visual patterns which did n o t instruct the monkey as to what the a p p r o p r i a t e action should be. The result of one of these e x p e r i m e n t s is shown in Fig. 5. In addition to the n o r m a l visual cue pattern. viz. a cursor and the vertical target line, a n o t h e r pattern. to which the m o n k e y had not been trained to respond, was included at r a n d o m in a sequence of trials. W i t h the presentation of the n o r m a l cue pattern. we o b t a i n e d the control response ( F i g . 5A). T h e test pattern, however, elicited no response (Fig 5B). F u r t h e r m o r e . when the cursor or the vertical target line w e r e p r e s e n t e d singly on the m o n i t o r (visual patterns to which the m o n k e y did not know how to respond), we observed no response or a greatly diminished r e s p o n s e . In experiments in which horizontal E O G s w e r e
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Fig. 5. Precentral unit responses to different visual patterns. In A, the response of a unit to the normal cue pattern is shown. B shows the response of the same unit to an unfamiliar visual pattern shown on the left. C shows the response of the unit to either the cursor or the vertical target line. The appearance of these patterns is marked by S. Bin width: 10 ms.
Variability of the visual cue response
ited excitatory responses and 26 inhibitory ones. Fig. 6A shows the latency distribution with respect to the onset of the visual cue. For the wrist ( F - E ) population the overall mean was 148 ms, and for the nonwiist ( F - E ) population the overall mean was 147 ms. There was no significant difference (t = 0.19, P < 0.05) between these two populations with respect to
A n u m b e r of statistical measures were used in our data analysis to detect any differences in variability between the two populations. The first one pertains to the response latencies. The response latencies from the two populations are shown in the relative frequency histograms of Fig. 6. The data shown were drawn from a total of 279 units, of which 253 exhib-
the sensory event. Fig. 6B shows the distribution of the response latencies with respect to the onset of movement. For the wrist ( F - E ) populations, the overall mean was - 1 0 4 ms, and for the non-wrist ( F - E ) population, it was -114 ms. Again, when these two populations were compared there was no significant difference between the means at the 5%
measured, we detected no temporal correlation between eye m o v e m e n t and the n e u r o n a l responses in the precentral forelimb area of the central cortex. This was true of both the wrist ( F - E ) and non-wrist ( F - E ) populations.
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0.26 for SDs; t = 1.40 for SDn, ) at the 5 % level. The validity of the foregoing comparisons is based on two necessary conditions23. The first is that the two populations have similar latencies of response. This condition was fulfilled by the data shown in Fig. 6. The second is that the two populations must show a similar relationship between latency and standard deviation. This relationship is examined in Fig. 8 for both of the populations with respect to the sensory event and the m o t o r event. These analyses indicated a roughly linear relationship between mean latency and the standard deviation, i. e. the standard deviation increased as the mean latency became longer. To visualize the differences between the ~wo populations, arbitrary b o u n d a r i e s were drawn (lower panels, Fig. 8). There is considerable overlap of the two populations in both instances This impression is confirmed by the fact that. for the sensory event, comparisons of the slope ( F = 0.59) and the e l e v a t i o n / F = 0.06) indicate no significant difference between the two populations at the 5% level. Analysis for the motor event (slope F = 0.19: elevation F = 1.01: P < 0.05) leads to a similar conclusion.
Proportions of task-related neurons
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Given the fact that the task primarily involved wrist e x t e n s i o n - f l e x i o n movement, one pertinenl question is w h e t h e r there was a difference in the proportion of cue-responsive neurons in the wrist ( F - E ) populations as c o m p a r e d to the non-wrist ( F - E ) populations. Table I presents data which address this question. The p r o p o r t i o n of cue-responswe neurons in the wrist ( F - E ) population a m o u n t e d to 55.4%. whereas the p r o p o r t i o n in the non-wrist f F - E ) population was equal to 42.8%. These figures, however.
31
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indicate that there is no significant difference in the proportion of task-related neurons between the two populations (X2 = 3.25; P < 0.05).
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Fig. 9 shows the distribution of the cortical loci at which responses triggered by the visual cue were observed. The data in this figure were derived from one of the two monkeys, and are presented with the cortex unfolded so as to reveal the organization deep within the central sulcus. The unfolding procedure and histological criteria for determination of the area 6 boundary have been described in detail previously 28. The region of loci controlling the wrist joint is outlined by the 'doughnut-shaped' area. A number of important observations can be made from these data. Firstly, the visual cue response was distributed only over the forelimb region of the precentral cortex, and it was not found in the non-forelimb (e.g. jaw or leg) regions. Secondly, the distribution of these loci was relatively uniform over the entire forelimb area with no preference to the wrist area, despite the fact that the wrist was the principal site of movement in this particular task. As indicated in Table I, a large proportion of the shoulder, elbow and finger neurons exhibited responsiveness to the visual cue. Thirdly, the visual cue response was observed in both cytoarchitectonic areas 4 and 6. DISCUSSION
Methodological considerations In the present study, the behaviour of two populations of neurons, viz. the wrist flexion-extension and the non-wrist flexion-extension populations, in a vis-
TABLE I
Proportions' of responsive neurons in different populations Population
Cue-responsive
Cue-unresponsive
Total
% Responsive
Non-wrist (F-E) Shoulder Elbow Wrist (other) Fingers Wrist (F-E)
248 70 79 46 53 31
332 123 94 49 66 25
580 193 173 95 119 56
42.8, 36.3 45.7 48.4 44.5 55.4
Total
279
357
636
43.9
32 H
N D . L I M B
servations confirm those of a recent study 27, in which the required movement was flexion and extension of the elbow• Furthermore, in this latter study, the observation of EMG activation was extended to the axial musculature as well. In those cases in which observations on non-wrist ( F - E ) units were made (e.g. Fig. 4B), it should be noted that a lack of specific temporal relationship between unit activities and wrist movement does not necessarily imply a lack of participation by these units in the specification of the movement. Indeed. these same units may, in part. contribute to the specification of non-wrist ( F - E ) muscle activities (Fig. 1) in a preparatory and supportive role.
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Fig. 9. Spatial distribution of the visual cue response in the unfolded precentral cortex from one monkey• T h e b o t t o m of the central sulcus is m a r k e d by the vertical line on the right representing 10 m m , and the broken vertical line in the centre indicates the crown of the precentral g y m s . T h e approximate medial-lateral boundary of the forelimb area is demarcated by the upper and lower horizontal broken lines• Small dots indicate the recording loci• Loci where the cue responses were observed are marked by large dots. The wrist zone is b o u n d e d by the distorted ring space•
ual-motor task was examined. There are a number of ways to classify neuronal populations in the precentral cortex. Some are anatomically oriented, in which neurons are classified by their projections, e.g. as pyramidal tract or non-pyramidal tract neurons. A more recent methodologic approach is the technique of spike-triggered averaging which allows a definition of the sphere of action of a precentral unit by the concept of 'motor field'6. In the present study a classification scheme which reflects the functional and spatial organization of the precentral motor cortex was adopted. This scheme is based on the recent observation of a nested organization in the primate precentral motor cortex 15,28. a finding which is supported by the results of Lemon 19 who duplicated parts of the experiments, and by a thorough study by Sessle and Wiesendanger 24.
EMG patterns It is interesting to note that even though the required movement in the present paradigm was wrist flexion or extension, forelimb muscles other than those of the wrist were activated reciprocally or bidirectionally in a supportive role (Fig. 1l. These ob-
Latency of response After the appearance of the vertical target line and the square cursor on the monitor, which is the eue for action, the mean of the reaction times for the two monkeys was 259 ms ( _+ 71 ms). These reaction times compare favorably with previous studies in which motor responses were triggered by a visual stimulus 4,9,23. The two delays which together contribute to the reaction time are the latency of the onset of the neuronal response with respect to the sensory event. VlZ. the cue. and the onset latency to the motor event. vlz. the wrist movement (Fig. 6), The mean response latency of the sensory event for both the wrist and the non-wrist populations was approximately 150 ms. These values of onset latency to visual stimulation are in agreement with previous unit studies in the precentral cortex 23.26. The field potential study of Gemba and coUeagues8 is of special interest in that they reported a visually evoked surface positive, depth negative potential of 40 ms latency in the pre-motor and motor areas bilaterally. This finding is in agreement with unit studies of Lamarre et al. 17,18and Murphy et a132 who reported a visually triggered response in the precentral cortex at a latency of 30-60 ms in reaction time paradigms In our present study, however, we did not observe unit responses with such a short latency. The latency difference may be accounted for by important differences between the experiments. The short (40 ms) latency response was observed in simple reaction time tasks triggered by relatively simple visual stimuli, In our experiments involving a choice reaction time task. the complex visual features embedded in
33 the cue may demand more processing for feature extraction, resulting in a more delayed response in precentral cortex. This latter possibility has also been suggested in a recent study by Lamarre and his coworkers~S.
Properties of the visual cue response An interesting observation concerning the visual cue response is that it was specific to the visual feature contained in the visual cue (Fig. 5). These neurons were responsive only to those visual stimuli which were related to the task at hand, and not related to non-specific stimuli such as flashes of light and moving objects. The visual cue response therefore, contains an element of context-dependence, which may have been 'shaped' locally or derived from other central nervous system structures involved in high-level visual feature extraction 12,16. A n o t h e r interesting aspect of the visual cue response was revealed by its spatial distribution in precentral cortex. As can be seen in Table I, the visual cue response was observed in about half of the forelimb neurons. In contrast, none of the identified nonforelimb cells exhibited the visual cue response (Fig. 9). Thus, in the performance of this visuomotor task, only a specific population of precentral neurons, viz. the neurons in the forelimb area, responded to the task relevant visual cue. The present study shows that cue responsive neurons are observed in both Brodmann area 4 and Brodmann area 6 cortex (Fig. 9). This result is in keeping with the suggestion that these areas are functionally continuous ~5. In a delayed response paradigm, Weinrich and Wise reported that visual signalrelated neurons were distributed exclusively in a premotor area defined by high-threshold ICMS (see Fig. 3 of ref. 26). To account for the apparent difference in observation, it is useful to note that there is considerable agreement that area 6 may play a role in the control of posture and of proximal musculature 2.3 (cf. H u m p h r e y 12 for review). This is also borne out by a study in primate precentrai cortical organization, in which area 6 shared a significant representation of the proximal musculature 15. Against this background, one may view those signal-related units exclusively found in premotor cortex in a delayed response task26 as neurons participating in the control of postural set (with sub- and suprathreshold man-
ifestations) in anticipation of the later 'go' signal when movement was required, during which the distal musculature was also involved. If the response had not been fragmented by the 'ready' and 'go' signals, one might have expected a more uniform distribution of the signal-related units over the motor cortex as well as the premotor area. It is of interest to note that in a similar delayed response paradigm, Weinrich and coworkers did later observe a significant proportion (approximately 20%, see Table I of ref. 27) of visual signal-related neurons in the precentral motor cortex (area 4). The lack of directional selectivity of the initial cue response, illustrated in Fig. 4, differs from the responses of wrist ( F - E ) neurons at a later phase in the task, which exhibited reciprocal responses to oppositely directed visual and somatic perturbations23,29, 30 (cf. Methods). This lack of directional selectivity differs again from the observations in other visuomotor paradigms. In one, the response of pyramidal tract neurons to a task-related photic stimulus depended upon the subsequent movement 4. In another, the response of neurons in precentral cortex to visual instruction reliably predicted the subsequent motor response 23. In attempting to reconcile these varied observations, an important point to consider is the context in which various observations were made: the character of the response may depend critically on the phase of a task, on the meaning of the visual signals, e.g. as in the use of 'ready' and 'go' signals, and on the complexity of the visual cue, e.g. simple reaction time vs choice reaction time. In the present experimental setting, the predominantly non-directional character of the visual cue response could perhaps be understood as serving a preparatory function paving the way for more selective responses during later phases of the task. As indicated in the results (Fig. 6), there was no significant difference in the response latencies of wrist ( F - E ) and the non-wrist ( F - E ) populations both with respect to the sensory event and the motor event. This observation is in accord with the results obtained in previous experiments in which response latencies to somatic perturbation and visual perturbation were assessed23, 29. When the variability of the cortical responses was examined in terms of the response index P, no signifi-
34 cant difference between the wrist and non-wrist populations was observed. In fact, this conclusion can be extended to the other two measures of response variability, viz. the standard deviations about the mean latency with respect to the sensory and m o t o r events (Fig. 7). H o w e v e r , at a later stage of this task when somatic and visual perturbations were applied, the wrist ( F - E ) population exhibited a lower response variability than the non-wrist ( F - E ) population 23.29. A final point concerning the p r o p e r t i e s of the visual cue response was the lack of a significant difference in the proportions of responsive neurons in the wrist and non-wrist populations (Table I). This observation again stands in sharp contrast to the result of the visual p e r t u r b a t i o n experiments 23 r e p o r t e d previously, in which a significantly greater p r o p o r tion of responsive neurons was observed in the wrist ( F - E ) population as c o m p a r e d to the non-wrist ( F - E ) population. W e m a y thus conclude that no preference was observed in terms of the timing variability and spatial distribution of the cue response, the very first precentral activity, when the two populations were c o m p a r e d , even though the task was one in which flexors and extensors of the wrist joint were the prime movers. It may be argued that the 'visual' properties of the cue response examined so far could be completely accounted for by the ' m o t o r ' properties as defined by
REFERENCES 1 Asanuma, H. and Sakata, H., Functional organization of a cortical efferent system examined with focal depth stimulation in cats, J. Neurophysiol., 30 (1967) 35-54. 2 Bucy, P. C., Electrical excitability and cyto-architecture of the premotor cortex in monkeys, Arch. Neurol. Psychiat., 30 (1933) 1205-1224. 3 Denny-Brown, D., The Cerebral Control of Movement, Liverpool Univ., Liverpool, 1966. 4 Evarts, E. V., Pyramidal tract activity associated with a conditioned hand movement in the monkey, J. Neurophysiol., 29 (1966) 1011-1027. 5 Evarts, E. V., Sensorimotor cortex activity associated with movement triggered by visual as compared to somesthetic inputs. In F. O. Schmidt (Ed.), Neuroscience Third Study Program, MIT Press, 1974, pp. 327-337. 6 Fetz, F. E., Cheney, P. D. and German, D. C., Corticomotoneuronal connections of precentral cells detected by postspike average of EMG activity in behaving monkeys, Brain Research, 114 (1976) 505-510. 7 Fromm, C. and Evarts, E. V., Relation of motor cortex neurons to precisely controlled and ballistic movements, Neurosci. Lett., 5 (1977) 259-265.
the subsequent movement. This contention is counte r m a n d e d by a n u m b e r of observations, however. Firstly, as shown in the results, the visual cue response was not a good predictor for the direction or timing (or sometimes the occurrence) of the subsequent m o v e m e n t (cf. Fig. 4A). Secondly, it was observed in a separate study23 that a great majority (87%) of neurons which exhibited reciprocal responses with respect to the direction of wrist movement after visual ' p e r t u r b a t i o n ' nevertheless responded bidirectionally to the preceding visual cue. F u r t h e r m o r e , 91% of these reciprocal neurons identified as belonging to the wrist ( F - E ) populations showed bidirectional cue responses 30. These observations are in support of the possibility that, by itself, the cue response in this p a r a d i g m does not completely specify the m o t o r manifestations of the animal (cf. ref. 25). T o g e t h e r with other sources of specification 12, however, it does contribute to the final m o t o r act. ACKNOWLEDGEMENTS W e wish to express our gratitude to Mr. H. N g u y e n - H u u for his c o m p u t e r expertise in the control of experiments and data acquisition. This work was supported by the Medical Research Council of Canada, G r a n t MT-4140.
8 Gemba, H., Hashimoto, S. and Sasaki, K., Cortical field potentials preceding visually initiated hand movements in the monkey, Exp. Brain Res., 42 (1981) 435-441. 9 Georgopoulous, A. P., Kalaska, J. F., Caminiti, R. and Massey, J. T., On the relations between the direction of two-dimensional aiming arm movements and cell discharge in primate motor cortex, J. Neurosci., 2 (1982) 1527-1537. 10 Godschalk, M., Lemon, R. N., Nijs, H. G. T. and Kuypers, H. G. J. M., Behaviour of neurons in monkey peri-arcuate and precentral cortex before and during visually guided arm and hand movements, Exp. Brain Res., 44 (1981) 113-116. 11 Hamada. I. and Kubota, K., Monkey pyramidal tract neurons and changes of movement parameters in visual tracking, Brain Res. Bull., 4 (1979) 249-257. 12 Humphrey, D. R., On the cortical controls of visually directed reaching. Contributions by nonprecentral motor areas. In R. E. Talbott and D. R. Humphrey (Eds.), Posture and Movement, Raven Press, New York, 1979, pp. 51-112. 13 Kubota, K. and Hamada, I., Visual tracking and neuron activity in the post-arcuate area in monkeys, J. Physiol. (Paris), 74 (1978) 297-312. 14 Kubota, K. and Hamada, I., Preparatory activity of mon-
35
15
16
17
18
19
20
key pyramidal tract neurons related to quick movement onset during visual tracking performance, Brain Research, 168 (1979) 435-439. Kwan, H. C., MacKay, W. A., Murphy, J. T. and Wong, Y. C.. Spatial organization of precentral cortex in awake primates. II. Motor outputs, J. Neurophysiol., 41 (1978) 1102-1131. Kwan, H. C., MacKay, W. A., Murphy, J. T. and Wong, Y. C., Distribution of responses to visual cues for movement in precentral cortex of awake primates, Neurosci. Lett., 24 (197i) 123-128. Lamarre, Y., Spidalieri, G. and Lund, J. P., Patterns of muscular and motor cortical activity during a simple arm movement in the monkey, Canad. J. Physiol. Pharmacol., 59 (1981) 748-756. Lamarre, Y., Busby, L. and Spidalieri, G., Fast ballistic arm movements triggered by visual, auditory, and somesthetic stimuli in the monkey. I. Activity of precentral cortical neurons, J. Neurophysiol., 50 (1983) 1343-1358. Lemon, R. N., Variety of functional organization within the monkey motor cortex, J. Physiol. (Lond.L 311 (1981) 521-540. MacPherson, J. M., Rasmusson, D. D. and Murphy, J. T., Activities of neurons in 'motor' thalamus during control of limb movements in the primate, J. Neurophysiol., 44 (1980) 11-20.
21 Matsunami, K. and Hamada, I., Characteristics of the ipsilateral movement-related neurons in the motor cortex of the monkey, Brain Research, 204 (1981) 29-42. 22 Murphy, J. T., Kwan, H. C., MacKay, W. A. and Wong, Y. C., Precentral unit activity correlated with angular components of a compound arm movement, Brain Research,
246 (1982) 141-145. 23 Murphy, J. T., Kwan, H. C., MacKay, W. A. and Wong, Y. C., Activity of primate precentral neurons during voluntary movements triggered by visual signals, Brain Research, 236 (1982) 429-449. 24 Sessle, B. J. and Wiesendanger, M., Structural and functional definition of the motor cortex in the monkey (Macaca fascicularis), J. Physiol. (Lond.), 323 (1982) 245-265. 25 Tanji, J. and Evarts, E. V., Anticipatory activity of motor cortex neurons in relation to direction of an intended movement, J. Neurophysiol,, 39 (1976) 1062-1068. 26 Weinrich, M. and Wise, S. P., The premotor cortex of the monkey, J. Neurosci., 2 (1982) 1329-1345. 27 Weinrich, M., Wise, S. P. and Mauritz, K.-H., A neurophysiological study of the premotor cortex in the rhesus monkey, Brain, 107 (1984) 385-414. 28 Wong, Y. C., Kwan, H. C., MacKay, W. A. and Murphy, J. T., Spatial organization of precentral cortex in awake primates. I. Somatosensory inputs, J. Neurophysiol., 41 (1978) 1107-1119. 29 Wong, Y. C., Kwan, H. C. and Murphy, J. T., Temporal characteristics of tongue-triggered neuronal responses in primate precentral cortex, Canad. J. Physiol. Pharmacol., 58 (1980) 778-786. 30 Wong, Y. C., Kwan, H. C., MacKay, W. A. and Murphy, J. T., Participation of precentral neurons in somatically and visually-triggered movements in primates, Brain Research, 247 (1982) 49-56. 31 Yumiya, H., Neuronal activity in cortical efferent zones projecting to wrist extensors during voluntary wrist extension in the monkey, Tohoku J. exp. Med., 121 (1977) 321-326.
24
-
Elsc~icl BRE 10988
Properties of Visual Cue Responses in Primate Precentral Cortex H. C. KWAN, W. A. MACKAY, J. T. MURPHY and Y. C. WONG
Department of Physiology, University of Toronto, Toronto, Ont. M5S 1A8 (Canada) (Accepted December llth, 1984)
Key words: precentral neuron - - visual stimulus - - monkey
Monkeys were trained to perform a visuomotor task involving the alignment of a cursor over a vertical target line on a videomonitor by flexion or extension movements of the wrist. The forelimb area of the contralateral precentral cortex was thoroughly explored during the task. Intracortical microstimulation was employed to classify the forelimb region into wrist flexion-extension and non-wrist flexion-extension populations. Unit recording revealed an initial response to the cue for movement, viz. the appearance of the cursor and target line on the videomonitor, while visual signals not related to the task failed to evoke any response. The mean latencyof these visual cue responses was approximately 150 ms, A great majority of the responses (96%) were bidirectional in character, in that they did not correlate with the directional information embedded in the visual cue, nor were they good predictors for the direction or timing of the subsequent movement. They were uniformly distributed in both the wrist and non-wrist regions of the forelimb area: the nonforelimb areas were devoid of the cue response. Further, when the variability of response to the visual cue for the wrist and non-wrist populations was compared, no significant difference was observed. These observations are consistent with an interpretation that the visually triggered cue responses provide a generalized activation over the task-related area of precentral cortex, paving the way for later and more specific activations leading to the execution of the task.
INTRODUCTION
In a r e c e n t series of e x p e r i m e n t s t6,23,29,30, we studied n e u r o n a l b e h a v i o r in p r e c e n t r a l c o r t e x in differ-
N u m e r o u s studies h a v e b e e n u n d e r t a k e n to e x a m ine the b e h a v i o r of n e u r o n s in the p r e c e n t r a t m o t o r c o r t e x d u r i n g a v i s u o m o t o r task4,5,7-1k13,14,17,21-23, 25.
ent phases of a v i s u o m o t o r task. w h i c h i n c l u d e d the initial p r e s e n t a t i o n of a cue for wrist flexion o r e x t e n sion m o v e m e n t , f o l l o w e d l a t e r by a visual o r s o m a t i c
26,30,31. A g e n e r a l c o n c l u s i o n e m e r g i n g f r o m t h e s e
' p e r t u r b a t i o n ' . In this r e p o r t , w e e x a m i n e the extent
studies is that the n a t u r e of the n e u r o n a l r e s p o n s e is
to which c o n t e x t - d e p e n d e n c e dictates b o t h t h e spa-
highly d e p e n d e n t on the n e u r o n a l t y p e f r o m which
tial and t e m p o r a l b e h a v i o r s of n e u r o n a l r e s p o n s e s
r e c o r d i n g s are m a d e and on t h e c o n t e x t in which the
triggered by the p r e s e n t a t i o n of a cue for m o v e m e n t
animal e x e c u t e s the v o l u n t a r y m o v e m e n t . F o r in-
in a task i n v o l v i n g flexion a n d e x t e n s i o n a b o u t the
stance, in o n e study 4 it was o b s e r v e d that p y r a m i d a l
'wrist. In particular, we c o m p a r e the p r o p e r t i e s o f a
tract n e u r o n s r e s p o n d e d to p h o t i c s t i m u l a t i o n if and
n e u r o n a l p o p u l a t i o n p u t a t i v e l y i d e n t i f i e d by intra-
only if the stimulus elicited a specific m o t o r r e s p o n s e .
cortical m i c r o s t i m u l a t i o n l , 15 as c o n t r o l l i n g wrist flex-
H o w e v e r , u n d e r a d i f f e r e n t set of e x p e r i m e n t a l cir-
ion or e x t e n s i o n m o v e m e n t with t h o s e of a n o t h e r
cumstances, m o d i f i c a t i o n of the cortical n e u r o n a l activity could be o b s e r v e d w i t h o u t any s u b s e q u e n t
p o p u l a t i o n which c o n t r o l s all o t h e r j o m t m o v e m e n t s of the f o r e l i m b .
m o d i f i c a t i o n of E M G 25. T h e s e o b s e r v a t i o n s highlight
A short c o m m u n i c a t i o n has b e e n published16,
the c o n t e x t - d e p e n d e n c e of p r e c e n t r a l n e u r o n a l responses to visual s t i m u l a t i o n , and p o i n t to the possi-
MATERIALS AND METHODS
bility that discharge of p r e c e n t r a l n e u r o n s m a y contribute to, but d o e s not necessarily l e a d to m o v e ment.
A d e t a i l e d d e s c r i p t i o n of the e x p e r i m e n t a l p a r a digm 20 has b e e n p r e s e n t e d previously. Briefly, two
Correspondence." H. C. Kwan, Department of Physiology. University of Toronto, Toronto, Ont. M5S 1A8. Canada. 0006-8993/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)
25 stump-tailed monkeys were trained to grasp a manipulandum connected to a torque motor. Flexion or extension of the wrist was translated into horizontal movement of a square cursor on a videomonitor which was placed 1 m from the animal. A vertical line, the position of which was computer controlled, was displayed on the monitor as well. The task of the monkey was to align the cursor over the vertical target line by means of either wrist flexion or extension movements. A fitted cast was placed around the forearm to minimize excessive movement of other joints than the wrist. The target line and cursor would then appear on the screen at random times. The appearance of the target line and cursor on the monitor, which constituted the cue for action, was then followed by alignment of the cursor over the target line. Under computer control this alignment was disturbed either by stepping the target line to the left or right of the cursor 23, or by a torque perturbation on the manipulandum which would dislodge the cursor from the target line 29. Successful realignment within a predetermined time period would lead to a juice or water reward. The present report will be concerned with the analysis of the precentral response during the initial phase of cue presentation.
was maintained below 3 k ~ to minimize m o v e m e n t artifact.
Classification of neurons A unit was classified as functionally related to a single joint by means of the criterion of intracortical microstimulation (ICMS) applied to the locus of recording 15. For instance, wrist extension (wrist-E) neurons were defined as those which, upon threshold ICMS at the recording locus, produced an extension movement about the wrist joint. The other class included shoulder, elbow, other-wrist (i.e. other than wrist flexion or extension), and finger neurons; this class was termed non-wrist (F-E) neurons. Wherever possible, the forelimb area was systematically explored in each monkey in order to reduce sampling bias for a certain region of the precentral cortex.
Histology Small electrolytic lesions were made at a number of recording sites upon completion of the series of experiments. Sixty-micron frozen serial sections were made and were later stained with cresyl violet. Recording loci were reconstructed on the basis of these electrolytic lesions, and in relation to cytoarchitectonic areas 4 and 6 28.
Data recording Upon completion of training, a burr hole was made in the skull over the precentral motor cortex and a stainless steel chamber was implanted under sterile conditions. The surgical methods for chronic recording have been fully described previously 28. Unit recordings from the precentral forelimb area were made over a period of 10 months. Glass-coated platinum-iridium microelectrodes with an average impedance of 0.5 MQ measured at 1 kHz were used. Units were discriminated in the conventional way using spike-height discrimination and sampled at 1 ms intervals. The displacement and velocity of the manipulandum were sampled at 10 ms intervals. In some recording sessions horizontal eye m o v e m e n t was monitored with surface disc E O G electrodes. During the initial phase of the experiments, E M G recording was performed to examine the patterns of discharge for the distal and proximal muscles participating in the task. Surface A g - A g C 1 electrodes (2 mm diameter) were used with an amplifier bandwidth of 50-1000 Hz. Electrode-to-skin impedance
Data analysis Data analysis, as detailed in our previous studies 23,29, was performed to detect differences in the response variability of the two populations of neurons in precentral cortex: wrist (F-E) and non-wrist (F-E) populations. The response of a neuron was defined as excitatory when the peristimulus time histogram (PSTH) showed two or more consecutive 10 ms bins, each containing a number of discharges exceeding two standard deviations (SD) about the mean number of discharges per bin in the prestimulus control period. In the case of inhibition, two sds below the mean control activity was employed as the criterion. Cells were then classified as task-related when modifications of discharge satisfied the above criteria. Two criteria were used to assess the variability of the response z3,29. First is the response index, P, which was defined as the ratio of responsive trials to the total number of trials. The second related to the variability of the timing of the onset of each response in single trials. The onset time of response in each
26 trial was defined by the onset time of the first spike in each response. These onset times were then used to / j'
compute the mean onset latencies with respect to the sensory event, Xs, and to the onset of the subsequent voluntary m o v e m e n t , X m , for all times. Correspond-
FLI ~Of
ing standard deviations, SD S and SD m, respectively, were also computed. x
LNSOR
RESULTS
EMG patterns A sample of E M G activities from proximal and distal muscles during wrist flexion and extension movements is shown in Fig. 1. The wrist prime movers in general exhibited reciprocal patterns of activation, while others were organized in a reciprocal or bidirectional fashion. Both transient and sustained temporal activations could be observed (Fig. 1). The onset of E M G activity ranged from 20 to 150 ms before the onset of m o v e m e n t , and activation of proximal muscles tended to precede that of more distal ones.
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Fig. 1. Full-wave rectified and smoothed EMGof selected forelimb muscles during a single flexion and extension wrist movement. The uppermost traces show wrist angular displacement of 15° in the flexion direction on the left, and 15° extension 0n~ the right. Onset of wrist movement occurs at time0i The arrow marks the time of cue presentation. Vertical scales on the right indicate an EMG amplitude of 0.2 mV:
Analysis of reaction time The relative frequency histogram of reaction time for all the trials (n = 3350) is shown in Fig. 2. Here the reaction time was defined as the time when the velocity changes from its resting zero value. After the appearance of the cursor and the target line which constituted the cue, the mean reaction time was 259 ms ( + 71 ms). The range of the reaction times varied from 140 to 410 ms. In a small n u m b e r of trials (about
A
B 20Y. -
: sd
2%) the reaction times were excessively prolonged (above 450 ms). These trials are not included in the present analysis.
259
=
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Temporal patterns of response Typical patterns of response to presentation of the visual cue are shown in Fig. 3. These patterns include phasic bursting responses as shown in A. those which exhibit a phasic c o m p o n e n t with a trailing tonic comp o n e n t as shown in D, and other intermediate patterns shown in B and C. Of the total 636 units identified somatotopically by means of ICMS, 279 units were found to be temporally correlated with the onset of the visual cue for movement. Of these. 90% showed excitatory responses while 10% showed inhibitory responses.
0 150
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V~ Fig. 2. Relative frequency histogram of reaction time. Vo, A: broken line indicates position of target line, and the solidline indicates cursor position and hence the hand position. The appearance of the cue occurs at the first arrow. The second arrow marks the time when the hand veloeity becomes.non-zero: this time is taken to be the reaction time. B: histogram of the reaction times, with mean latency, x, and standard deviation, sd. These abbreviations apply to all subsequent figures.Bin width is 10 ms. Horizontal axis: time after cue presentation (msl.
27
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Relation to the visual cue and the direction o f move-
tions o v e r the e n t i r e f o r e l i m b a r e a (Fig. 9). A n e x a m -
ment A great m a j o r i t y ( 9 4 % ) of the units which re-
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s h o w e d two i n t e r e s t i n g f e a t u r e s . Firstly, t h e r e was in g e n e r a l a lack of c o r r e l a t i o n b e t w e e n these r e s p o n s e s and the d i r e c t i o n a l i n f o r m a t i o n c o n t a i n e d in the visual cue. S e c o n d l y , t h e r e was an a d d i t i o n a l lack of cor-
at this locus p r o d u c e d a wrist e x t e n s i o n m o v e m e n t , this unit re-
s p o n d e d to passive wrist flexion. Fig. 4B shows a non-wrist ( s h o u l d e r - e x t e n s i o n ) unit r e c o r d e d at a s e p a r a t e locus with a phasic plus
relation b e t w e e n the r e s p o n s e s and the d i r e c t i o n of
tonic p a t t e r n similar to that of Fig. 3D. In this set of trials, while the r e s p o n s e s to the cue w e r e f o l l o w e d
the s u b s e q u e n t m o v e m e n t , T h e s e r e s p o n s e s can be
by m o v e m e n t s of the wrist in e i t h e r d i r e c t i o n , these
d e s c r i b e d as bidirectional. T h e y w e r e o b s e r v e d in
m o v e m e n t s o c c u r r e d at v a r i a b l e times. As an e x a m -
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presentation, followed by a second burst which preceded the cessation of flexion m o v e m e n t . A n o t h e r example is found in trial 12. in which the cue response merged into a later and further increase in discharge, which was followed by an extension m o v e m e n t .
Context-dependent nature of the response The non-specific nature of the visually triggered cue response raises the possibility that these responses in the precentral cortex were merely startle responses and were not related to the task at hand. A n alternative possibility is that these responses were t e m p o r a l l y c o r r e l a t e d with the E O G rather than the sensory cue. To examine the first possibility, we used bright flashes of light in an effort to e v o k e responses in precentral neurons. These efforts proved to be futile. In o t h e r e x p e r i m e n t s , we p r e s e n t e d 'un-
familiar' visual patterns to the m o n k e y on t h e video monitor, i.e. visual patterns which did n o t instruct the monkey as to what the a p p r o p r i a t e action should be. The result of one of these e x p e r i m e n t s is shown in Fig. 5. In addition to the n o r m a l visual cue pattern. viz. a cursor and the vertical target line, a n o t h e r pattern. to which the m o n k e y had not been trained to respond, was included at r a n d o m in a sequence of trials. W i t h the presentation of the n o r m a l cue pattern. we o b t a i n e d the control response ( F i g . 5A). T h e test pattern, however, elicited no response (Fig 5B). F u r t h e r m o r e . when the cursor or the vertical target line w e r e p r e s e n t e d singly on the m o n i t o r (visual patterns to which the m o n k e y did not know how to respond), we observed no response or a greatly diminished r e s p o n s e . In experiments in which horizontal E O G s w e r e
29
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Variability of the visual cue response
ited excitatory responses and 26 inhibitory ones. Fig. 6A shows the latency distribution with respect to the onset of the visual cue. For the wrist ( F - E ) population the overall mean was 148 ms, and for the nonwiist ( F - E ) population the overall mean was 147 ms. There was no significant difference (t = 0.19, P < 0.05) between these two populations with respect to
A n u m b e r of statistical measures were used in our data analysis to detect any differences in variability between the two populations. The first one pertains to the response latencies. The response latencies from the two populations are shown in the relative frequency histograms of Fig. 6. The data shown were drawn from a total of 279 units, of which 253 exhib-
the sensory event. Fig. 6B shows the distribution of the response latencies with respect to the onset of movement. For the wrist ( F - E ) populations, the overall mean was - 1 0 4 ms, and for the non-wrist ( F - E ) population, it was -114 ms. Again, when these two populations were compared there was no significant difference between the means at the 5%
measured, we detected no temporal correlation between eye m o v e m e n t and the n e u r o n a l responses in the precentral forelimb area of the central cortex. This was true of both the wrist ( F - E ) and non-wrist ( F - E ) populations.
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Fig. 7. Measures of response variability. Relative frequency histogram for the response index (P) is shown in A, for the standard deviation about the mean latency With res~ct to the sensory event (SDs) in B, and with respect to the motor event (SDra) in C. The upper panels were derived from the wrist (F-E) population, and the lower, from the non-wrist (F-E) population. Abscissae in A indicate values of the response index P, and in B and C, values Of standard deviations in ms.
Given the fact that the task primarily involved wrist e x t e n s i o n - f l e x i o n movement, one pertinenl question is w h e t h e r there was a difference in the proportion of cue-responsive neurons in the wrist ( F - E ) populations as c o m p a r e d to the non-wrist ( F - E ) populations. Table I presents data which address this question. The p r o p o r t i o n of cue-responswe neurons in the wrist ( F - E ) population a m o u n t e d to 55.4%. whereas the p r o p o r t i o n in the non-wrist f F - E ) population was equal to 42.8%. These figures, however.
31
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indicate that there is no significant difference in the proportion of task-related neurons between the two populations (X2 = 3.25; P < 0.05).
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Fig. 9 shows the distribution of the cortical loci at which responses triggered by the visual cue were observed. The data in this figure were derived from one of the two monkeys, and are presented with the cortex unfolded so as to reveal the organization deep within the central sulcus. The unfolding procedure and histological criteria for determination of the area 6 boundary have been described in detail previously 28. The region of loci controlling the wrist joint is outlined by the 'doughnut-shaped' area. A number of important observations can be made from these data. Firstly, the visual cue response was distributed only over the forelimb region of the precentral cortex, and it was not found in the non-forelimb (e.g. jaw or leg) regions. Secondly, the distribution of these loci was relatively uniform over the entire forelimb area with no preference to the wrist area, despite the fact that the wrist was the principal site of movement in this particular task. As indicated in Table I, a large proportion of the shoulder, elbow and finger neurons exhibited responsiveness to the visual cue. Thirdly, the visual cue response was observed in both cytoarchitectonic areas 4 and 6. DISCUSSION
Methodological considerations In the present study, the behaviour of two populations of neurons, viz. the wrist flexion-extension and the non-wrist flexion-extension populations, in a vis-
TABLE I
Proportions' of responsive neurons in different populations Population
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Cue-unresponsive
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% Responsive
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248 70 79 46 53 31
332 123 94 49 66 25
580 193 173 95 119 56
42.8, 36.3 45.7 48.4 44.5 55.4
Total
279
357
636
43.9
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servations confirm those of a recent study 27, in which the required movement was flexion and extension of the elbow• Furthermore, in this latter study, the observation of EMG activation was extended to the axial musculature as well. In those cases in which observations on non-wrist ( F - E ) units were made (e.g. Fig. 4B), it should be noted that a lack of specific temporal relationship between unit activities and wrist movement does not necessarily imply a lack of participation by these units in the specification of the movement. Indeed. these same units may, in part. contribute to the specification of non-wrist ( F - E ) muscle activities (Fig. 1) in a preparatory and supportive role.
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Fig. 9. Spatial distribution of the visual cue response in the unfolded precentral cortex from one monkey• T h e b o t t o m of the central sulcus is m a r k e d by the vertical line on the right representing 10 m m , and the broken vertical line in the centre indicates the crown of the precentral g y m s . T h e approximate medial-lateral boundary of the forelimb area is demarcated by the upper and lower horizontal broken lines• Small dots indicate the recording loci• Loci where the cue responses were observed are marked by large dots. The wrist zone is b o u n d e d by the distorted ring space•
ual-motor task was examined. There are a number of ways to classify neuronal populations in the precentral cortex. Some are anatomically oriented, in which neurons are classified by their projections, e.g. as pyramidal tract or non-pyramidal tract neurons. A more recent methodologic approach is the technique of spike-triggered averaging which allows a definition of the sphere of action of a precentral unit by the concept of 'motor field'6. In the present study a classification scheme which reflects the functional and spatial organization of the precentral motor cortex was adopted. This scheme is based on the recent observation of a nested organization in the primate precentral motor cortex 15,28. a finding which is supported by the results of Lemon 19 who duplicated parts of the experiments, and by a thorough study by Sessle and Wiesendanger 24.
EMG patterns It is interesting to note that even though the required movement in the present paradigm was wrist flexion or extension, forelimb muscles other than those of the wrist were activated reciprocally or bidirectionally in a supportive role (Fig. 1l. These ob-
Latency of response After the appearance of the vertical target line and the square cursor on the monitor, which is the eue for action, the mean of the reaction times for the two monkeys was 259 ms ( _+ 71 ms). These reaction times compare favorably with previous studies in which motor responses were triggered by a visual stimulus 4,9,23. The two delays which together contribute to the reaction time are the latency of the onset of the neuronal response with respect to the sensory event. VlZ. the cue. and the onset latency to the motor event. vlz. the wrist movement (Fig. 6), The mean response latency of the sensory event for both the wrist and the non-wrist populations was approximately 150 ms. These values of onset latency to visual stimulation are in agreement with previous unit studies in the precentral cortex 23.26. The field potential study of Gemba and coUeagues8 is of special interest in that they reported a visually evoked surface positive, depth negative potential of 40 ms latency in the pre-motor and motor areas bilaterally. This finding is in agreement with unit studies of Lamarre et al. 17,18and Murphy et a132 who reported a visually triggered response in the precentral cortex at a latency of 30-60 ms in reaction time paradigms In our present study, however, we did not observe unit responses with such a short latency. The latency difference may be accounted for by important differences between the experiments. The short (40 ms) latency response was observed in simple reaction time tasks triggered by relatively simple visual stimuli, In our experiments involving a choice reaction time task. the complex visual features embedded in
33 the cue may demand more processing for feature extraction, resulting in a more delayed response in precentral cortex. This latter possibility has also been suggested in a recent study by Lamarre and his coworkers~S.
Properties of the visual cue response An interesting observation concerning the visual cue response is that it was specific to the visual feature contained in the visual cue (Fig. 5). These neurons were responsive only to those visual stimuli which were related to the task at hand, and not related to non-specific stimuli such as flashes of light and moving objects. The visual cue response therefore, contains an element of context-dependence, which may have been 'shaped' locally or derived from other central nervous system structures involved in high-level visual feature extraction 12,16. A n o t h e r interesting aspect of the visual cue response was revealed by its spatial distribution in precentral cortex. As can be seen in Table I, the visual cue response was observed in about half of the forelimb neurons. In contrast, none of the identified nonforelimb cells exhibited the visual cue response (Fig. 9). Thus, in the performance of this visuomotor task, only a specific population of precentral neurons, viz. the neurons in the forelimb area, responded to the task relevant visual cue. The present study shows that cue responsive neurons are observed in both Brodmann area 4 and Brodmann area 6 cortex (Fig. 9). This result is in keeping with the suggestion that these areas are functionally continuous ~5. In a delayed response paradigm, Weinrich and Wise reported that visual signalrelated neurons were distributed exclusively in a premotor area defined by high-threshold ICMS (see Fig. 3 of ref. 26). To account for the apparent difference in observation, it is useful to note that there is considerable agreement that area 6 may play a role in the control of posture and of proximal musculature 2.3 (cf. H u m p h r e y 12 for review). This is also borne out by a study in primate precentrai cortical organization, in which area 6 shared a significant representation of the proximal musculature 15. Against this background, one may view those signal-related units exclusively found in premotor cortex in a delayed response task26 as neurons participating in the control of postural set (with sub- and suprathreshold man-
ifestations) in anticipation of the later 'go' signal when movement was required, during which the distal musculature was also involved. If the response had not been fragmented by the 'ready' and 'go' signals, one might have expected a more uniform distribution of the signal-related units over the motor cortex as well as the premotor area. It is of interest to note that in a similar delayed response paradigm, Weinrich and coworkers did later observe a significant proportion (approximately 20%, see Table I of ref. 27) of visual signal-related neurons in the precentral motor cortex (area 4). The lack of directional selectivity of the initial cue response, illustrated in Fig. 4, differs from the responses of wrist ( F - E ) neurons at a later phase in the task, which exhibited reciprocal responses to oppositely directed visual and somatic perturbations23,29, 30 (cf. Methods). This lack of directional selectivity differs again from the observations in other visuomotor paradigms. In one, the response of pyramidal tract neurons to a task-related photic stimulus depended upon the subsequent movement 4. In another, the response of neurons in precentral cortex to visual instruction reliably predicted the subsequent motor response 23. In attempting to reconcile these varied observations, an important point to consider is the context in which various observations were made: the character of the response may depend critically on the phase of a task, on the meaning of the visual signals, e.g. as in the use of 'ready' and 'go' signals, and on the complexity of the visual cue, e.g. simple reaction time vs choice reaction time. In the present experimental setting, the predominantly non-directional character of the visual cue response could perhaps be understood as serving a preparatory function paving the way for more selective responses during later phases of the task. As indicated in the results (Fig. 6), there was no significant difference in the response latencies of wrist ( F - E ) and the non-wrist ( F - E ) populations both with respect to the sensory event and the motor event. This observation is in accord with the results obtained in previous experiments in which response latencies to somatic perturbation and visual perturbation were assessed23, 29. When the variability of the cortical responses was examined in terms of the response index P, no signifi-
34 cant difference between the wrist and non-wrist populations was observed. In fact, this conclusion can be extended to the other two measures of response variability, viz. the standard deviations about the mean latency with respect to the sensory and m o t o r events (Fig. 7). H o w e v e r , at a later stage of this task when somatic and visual perturbations were applied, the wrist ( F - E ) population exhibited a lower response variability than the non-wrist ( F - E ) population 23.29. A final point concerning the p r o p e r t i e s of the visual cue response was the lack of a significant difference in the proportions of responsive neurons in the wrist and non-wrist populations (Table I). This observation again stands in sharp contrast to the result of the visual p e r t u r b a t i o n experiments 23 r e p o r t e d previously, in which a significantly greater p r o p o r tion of responsive neurons was observed in the wrist ( F - E ) population as c o m p a r e d to the non-wrist ( F - E ) population. W e m a y thus conclude that no preference was observed in terms of the timing variability and spatial distribution of the cue response, the very first precentral activity, when the two populations were c o m p a r e d , even though the task was one in which flexors and extensors of the wrist joint were the prime movers. It may be argued that the 'visual' properties of the cue response examined so far could be completely accounted for by the ' m o t o r ' properties as defined by
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the subsequent movement. This contention is counte r m a n d e d by a n u m b e r of observations, however. Firstly, as shown in the results, the visual cue response was not a good predictor for the direction or timing (or sometimes the occurrence) of the subsequent m o v e m e n t (cf. Fig. 4A). Secondly, it was observed in a separate study23 that a great majority (87%) of neurons which exhibited reciprocal responses with respect to the direction of wrist movement after visual ' p e r t u r b a t i o n ' nevertheless responded bidirectionally to the preceding visual cue. F u r t h e r m o r e , 91% of these reciprocal neurons identified as belonging to the wrist ( F - E ) populations showed bidirectional cue responses 30. These observations are in support of the possibility that, by itself, the cue response in this p a r a d i g m does not completely specify the m o t o r manifestations of the animal (cf. ref. 25). T o g e t h e r with other sources of specification 12, however, it does contribute to the final m o t o r act. ACKNOWLEDGEMENTS W e wish to express our gratitude to Mr. H. N g u y e n - H u u for his c o m p u t e r expertise in the control of experiments and data acquisition. This work was supported by the Medical Research Council of Canada, G r a n t MT-4140.
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