Brain Research, 88 (1975) 99-104 's) Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
99
Cortical potentials associated with voluntary movements in the monkey
JOSEPH AREZZO AND HERBERT G. V A U G H A N , JR.*
Departments of Neuroscience and Neurology, and the Rose F. Kennedy Center for Research ht Mental Retardation and Haman Development, Albert Einstein College of Medicine, Bronx, N.Y. 10461 (U.S.A.)
(Accepted January 14th, 1975)
Phasic negative potentials preceding voluntary hand and foot movements have been recorded from the human scalp overlying precentral motor cortex by averaging the E E G activity associated with repetitive self-paced contractions2, 6,t~ and in stimulus triggered reaction time taskslL The timing and topographic distribution of these potentials suggest that they might reflect postsynaptic activity of neurons in precentral motor cortex associated with the initiation of voluntary movements. In self-paced tasks the ' m o t o r potentials' (MPs) presented a complex waveform comprising 3 major components: an early slow shift (N1) 13 or 'readiness potential 'v, which began as much as a second before the muscle contraction; the phasic negative wave (N2) which preceded the contraction by a variable interval dependent upon the distance from cortex to muscle13; and a large positive wave (P2) which was roughly concurrent with the contraction. Although Vaughan et al. 13 found all of these components largest over the central cortex contralateral to movements of the extremities, other investigators have described somewhat different timing and spatial distributions 2,5. Gerbrandt et al. '~ reported that the phasic negativity began after the onset of movement and questioned the notion that these potentials reflected efferent processes. The present study was intended to precisely define the morphology and timing of the MPs and to identify their sites of origin utilizing direct recordings from the cortex of behaving monkeys. These data, which can be related to extracellular single unit recordings of movement related cortical activity3,4, l°, would provide a sounder basis for interpretation of the possible functional significance of the components of the human MP. Four adult macaques ( M . mulatta) were trained according to a variable ratio schedule of reinforcement to perform repetitive wrist extension movements at intervals exceeding 2 sec. After training, arrays of up to 60 epidural electrodes were implanted over the dorsolateral surface of the cortex both ipsilateral and contralateral to the contracting arm. The epidural electrodes were 20-gauge stainless steel tubes, insulated except at the end in apposition to the dura. The tubes also served as guides for * To whom requests for reprints should be addressed.
I00 depth electrodes which were moved by a microdrive through the underlying cortex. After recording the MP from the entire array of epidural placements, intracort~cal recordings were taken at incremental depths to determine the pattern of activit? ~n relation to the cortical layers. Fixed electrodes were also placed deep to the cortex so as to permit concurrent transcortical recordings from several sites. We employed the criterion of transcortical inversion of a specific MP component to deline the regiolts involved in its generation. The depth of inversion was related, after sacrifice, to the laminar cortical architecture. The brain potentials were amplified employing Tektronix 3A9 differential amplifiers set for a band-pass (down 3 dB) from 0. I to 300 Hz. Due to the electrode characteristics, the effective time constant of the recording system was reduced to approximately 500 msec. The extensor E M G associated with the wrist movements was rectified and its rising phase employed to synchronize the brain potentials in relation to the movementb, Each MP represented the averaged brain activity synchronized with a series of 200 successive contractions over a period 400 msec preceding and following the onset of the E M G activity. In Fig. 1, typical contralateral MP waveforms are depicted for wrist extension movements in a human subject and in a monkey. The morphology of the two potentials is essentially the same, although the duration of the monkey MP as well as the muscle
~OCOCO
P2
5o..[_ Homo
"1 Fig. 1. MPs associated with self-paced wrist extension movements recorded from the scalp of a human subject and the dura of a monkey precentra] motor cortex. The rectified and averaged E M G is displayed below each MP. Note the differences in time and amplitude scales.
101 contraction, is shorter than in the human subject performing a comparable movement. The initial slow negative shift (NI) can be seen in the monkey MP but the limited frequency response of the recording system has attenuated its size. The phasic negativity (N2) begins at a mean of 90 msec (range 85-110 msec) prior to EMG onset and is occasionally preceded by a small positive wavelet (PI). This component was not seen on all runs, but when present it displayed a reliable timing and was therefore identified as a distinct component which corresponds to the small and inconstant PI deflection of the human MP 13. N2 is followed by a positive deflection with two peaks; the first at 150 msec (range 132-173 msec) and the second at 265 msec (range 250-300 msec). This double-peaked configuration of the late positivity was not mentioned in the earlier human studies, but a review of our data shows this to be a frequent finding in human MPs, as depicted in Fig. 1. We have designated these late peaks P2 and P3 :::. The same configuration was found in all 4 monkeys for the discrete wrist extension. When the movement was altered to include both active extension and flexion, the waveform was prolonged and the later components became more complex. The antecedent components of the MP are sharply reduced in amplitude overlying the ipsilateral hemisphere. NI is completely absent from ipsilateral recordings while the N2 component is limited to electrode sites immediately anterior to the central sulcus and reached a maximal amplitude less than 30 o~, of the maximal contralateral N2. P2 is also predominantly contralateral but P3 is symmetrical in distribution over the two hemispheres. The contralateral epidural amplitude distributions of N2, P2 and P3 are depicted as isopotential maps in Fig. 2. Although there is some overlap, the potential distributions differ for each component. The N2 distribution is quite circumscribed with its maximum overlying the hand area of precentral motor cortex. Although N1 was not mapped in detail, its distribution is roughly comparable to that of N2. The P2 distribution overlies both pre- and postcentral cortex including the N2 distribution within its boundaries. P3, in contrast, is more medially distributed and, as previously mentioned, bilaterally symmetrical. Each of the MP components inverted in polarity from surface to subcortical recordings within regions underlying the maxima of its epidural distribution (Fig. 3); N2 is clearly restricted to the hand area of precentral cortex, P2 is generated both in pre- and postcentral cortex, whereas P3 is generated solely within area 5. Although our laminar analyses are not yet complete, the antecedent MP activity inverts in polarity deeply, across laminae 4 and 5, while the P2 and P3 components invert more superficially. This finding appears to support the recent observations of Asanuma and Rosen 1 as to the functional organization of precentral cortex. The morphology and distribution of the monkey MP are in substantial agreement with our earlier studies of the human MP ~3. The precise localization of the N2 component to the precentral motor cortex lends strong support to the conclusion,
* We favor a serial numbering of MP peaks rather than the terminology introduced by Deecke et al.=', since the latter ascribes a functional significance to the individual waves which is not yet supported by empirical evidence. Note that the designation of the long latency component of the MP as P3 does not imply that it is functionally related to the P3 phenomena in sensory evoked potentials.
102
EMG
/~.~___
Fig. 2. Epidural amplitude distributions for the N2, P2 and P3 components of the contralateral MP in one monkey. The isopotential lines represent 90, 80, 65 and 50~ of the maximal baseline to peak voltage of each component.
based upon scalp topography, that the human N2 component is generated exclusively in the precentral gyrus. Similarly, the presence of generators of P2 in both pre- and postcentral cortex confirms our assertion concerning the sources of the comparable human MP component. The finding of bilateral sources in area 5 for the later positive wave (P3) which was distinguished from the earlier positivity in the human studies, is a new discovery. The localization and timing of the gross MP components can be compared to the temporal pattern of single unit activity recorded during voluntary movements in the monkey. Although most of the single unit studies have utilized a stimulus triggered
103 INVERSION NO INVERSION
dura
°ii"
21~MSEC
EMG
Fig. 3. Recording sites which yielded evidence of active response in underlying surface cortex. Loci showing transcortical polarity inversions of the component indicated by the arrows are depicted as solid circles, and placements which revealed only volume conducted activity are indicated by open circles. Composite of recordings from 2 monkeys. Overlapping sites which revealed the same results in both monkeys have been deleted. task rather than self-paced contractions employed here, it is clear that the N2 c o m p o nent o f the MP closely corresponds to the time course o f precentral unit activity and arises from the same cortical sites. Similarly, as recently reported by Schmidt et al. l°, the slow shift, N I , is concurrent with a gradual increase in firing o f some o f the same neurons which participate in the phasic premovement discharge. In the present study we found no evidence o f activity related to m o v e m e n t in frontal granular cortex as described by K u b o t a and Niki 8 in a delayed alternation task. Thus, it appears that the D R L task may involve different mechanisms o f m o v e m e n t initiation than delayed alternation. The pre- and postcentral origins o f P2 raise some questions in relation to the reports by Evarts 3,4 on the timing o f pre- and postcentral units. His studies have disclosed little late spike activity from precentral cortex, and the postcentral unit activity
104 subsided earlier t h a n P2. l h u s , we have identified gross cortical potentials generaied in both the precentral a n d poslcentral region for which there as yet exists no demonstraled c o u n t e r p a r t in single n e u r o n recordings. F u r t h e r m o r e , the precentral distribution ot s o m a t o s e n s o r y evoked potentials, recorded from the monkeys studied here, is tinmed to the a n t e r i o r b a n k of the central fissure (unpublished observations), II appears that the peripheral afferents do not extend as widely as the region involved in the generation of P2 and therefore we speculate that P2 reflects, in part, a central feedback mechanism as was suggested by our earlier results in deafferented monkeys ~ Finally, the late positivity (P3) derives from an area of cortex which has, in llle alert monkey, a distinctive somatosensory input described by Sakata ~'l al. 9. its long latency (over 200 msec after the onset of the movement) and bilateral representation are in c o n f o r m i t y with the timing a n d spatial properties of area 5 n e u r o n s in response to somesthetic inputs. O u r tindings of area 5 activity related to active m o t i o n tends to s u p p o r t the suggestion by Sakata el al. 'a that this region might encode i n f o r m a l i o n on body position. This work was supported by G r a n t GB-35596 from the National Science F o u n d a t i o n , G r a n t MH06723 from N I M H , and G r a n t HD-01799 from N I H .
1 ASANUMA, H., AND ROSEN, I., Functional role of afferent inputs to the monkey motor cortex, Brain Research, 40 (1972) 3 5.
2 DEECKE,L., SCHEID, P., AND KORNHUaER,H. H., Distribution of readiness potential, pre-motion positivity, and motor potential of the human cerebral cortex preceding voluntary finger movements, Exp. Brain Res., 7 (1969) 158-168. 3 EVARTS,E. V., Contrasts between activity of precentral and postcentral neurons of cerebral cortex during movement in the monkey, Brain Research, 40 (1972) 25 31. 4 EVARTS,E. V., Precentral and postcentral cortical activity in association with visually triggered movement, J. Neurophysiol., 37 (1974) 373-381. 5 GERnnANDT,L. K., Govv, W. R., ANDSMITH,D. B., Distribution of the human average movenlent potential, Electroeneeph. olin. Neurophysiol., 34 (1973)461-474. 6 GILDEN, L., VAUGHAN,H. G., JR., AND COSTA, L. D., Summated human EEG potentials associated with voluntary movement, Electroenceph. din. Neurophysiol., 20 (1966) 433-438. 7 KORNHUBER, H. H., ONO DEECKE, L., Hirnpotentialfinderungen bei Willktirbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale, pttiiger.s Areh. ges. PhysioL, 284 (11965) 1-17. 8 KOBOTA,K., AND NIKI, H., Prefrontal cortical unit activity and delayed alternation performance in monkeys, J. Neurophysiol., 34 (1971) 337-347. 9 SAKATA,H., TAKAOKA,Y., KAWARASAKJ,A., AND SHmUTANI,H., Somatosensory properties of neurons in the superior parietal cortex (area 5) of the rhesus monkey, Brain Research, 64 (1973) 85-102. 10 SCHMIDT,E. M., JOST, R. G., AND DAVIS,K. K., Cortical cell discharge patterns in anticipation of a trained movement, Brain Research, 75 (1974) 309-311. I 1 VAUGHAN,n. G., JR., BO,SSOM,J., AND GROSS, E. G., Cortical motor potential in monkeys before and after upper limb deafferentation, Exp. Neurol., 26 (1970) 253-262. 12 VAUGHAN,H. G., JR., COSTA, L. D., (JILDEN, L., AND SCHIMMEL,H., Identification of sensory and motor components of cerebral activity in simple reaction-time tasks, Proc. 73rd Cony. Anwr. P~3,chol. Ass., 1 (1965) 179-t80. 13 VAUGHAN,H. G., JR., COSTA,L. D., AND RITTER,W., Topography of the human motor potential, Electroem'eph, clin. NeurophysioL, 25 (I 968) I- 10.
99
Cortical potentials associated with voluntary movements in the monkey
JOSEPH AREZZO AND HERBERT G. V A U G H A N , JR.*
Departments of Neuroscience and Neurology, and the Rose F. Kennedy Center for Research ht Mental Retardation and Haman Development, Albert Einstein College of Medicine, Bronx, N.Y. 10461 (U.S.A.)
(Accepted January 14th, 1975)
Phasic negative potentials preceding voluntary hand and foot movements have been recorded from the human scalp overlying precentral motor cortex by averaging the E E G activity associated with repetitive self-paced contractions2, 6,t~ and in stimulus triggered reaction time taskslL The timing and topographic distribution of these potentials suggest that they might reflect postsynaptic activity of neurons in precentral motor cortex associated with the initiation of voluntary movements. In self-paced tasks the ' m o t o r potentials' (MPs) presented a complex waveform comprising 3 major components: an early slow shift (N1) 13 or 'readiness potential 'v, which began as much as a second before the muscle contraction; the phasic negative wave (N2) which preceded the contraction by a variable interval dependent upon the distance from cortex to muscle13; and a large positive wave (P2) which was roughly concurrent with the contraction. Although Vaughan et al. 13 found all of these components largest over the central cortex contralateral to movements of the extremities, other investigators have described somewhat different timing and spatial distributions 2,5. Gerbrandt et al. '~ reported that the phasic negativity began after the onset of movement and questioned the notion that these potentials reflected efferent processes. The present study was intended to precisely define the morphology and timing of the MPs and to identify their sites of origin utilizing direct recordings from the cortex of behaving monkeys. These data, which can be related to extracellular single unit recordings of movement related cortical activity3,4, l°, would provide a sounder basis for interpretation of the possible functional significance of the components of the human MP. Four adult macaques ( M . mulatta) were trained according to a variable ratio schedule of reinforcement to perform repetitive wrist extension movements at intervals exceeding 2 sec. After training, arrays of up to 60 epidural electrodes were implanted over the dorsolateral surface of the cortex both ipsilateral and contralateral to the contracting arm. The epidural electrodes were 20-gauge stainless steel tubes, insulated except at the end in apposition to the dura. The tubes also served as guides for * To whom requests for reprints should be addressed.
I00 depth electrodes which were moved by a microdrive through the underlying cortex. After recording the MP from the entire array of epidural placements, intracort~cal recordings were taken at incremental depths to determine the pattern of activit? ~n relation to the cortical layers. Fixed electrodes were also placed deep to the cortex so as to permit concurrent transcortical recordings from several sites. We employed the criterion of transcortical inversion of a specific MP component to deline the regiolts involved in its generation. The depth of inversion was related, after sacrifice, to the laminar cortical architecture. The brain potentials were amplified employing Tektronix 3A9 differential amplifiers set for a band-pass (down 3 dB) from 0. I to 300 Hz. Due to the electrode characteristics, the effective time constant of the recording system was reduced to approximately 500 msec. The extensor E M G associated with the wrist movements was rectified and its rising phase employed to synchronize the brain potentials in relation to the movementb, Each MP represented the averaged brain activity synchronized with a series of 200 successive contractions over a period 400 msec preceding and following the onset of the E M G activity. In Fig. 1, typical contralateral MP waveforms are depicted for wrist extension movements in a human subject and in a monkey. The morphology of the two potentials is essentially the same, although the duration of the monkey MP as well as the muscle
~OCOCO
P2
5o..[_ Homo
"1 Fig. 1. MPs associated with self-paced wrist extension movements recorded from the scalp of a human subject and the dura of a monkey precentra] motor cortex. The rectified and averaged E M G is displayed below each MP. Note the differences in time and amplitude scales.
101 contraction, is shorter than in the human subject performing a comparable movement. The initial slow negative shift (NI) can be seen in the monkey MP but the limited frequency response of the recording system has attenuated its size. The phasic negativity (N2) begins at a mean of 90 msec (range 85-110 msec) prior to EMG onset and is occasionally preceded by a small positive wavelet (PI). This component was not seen on all runs, but when present it displayed a reliable timing and was therefore identified as a distinct component which corresponds to the small and inconstant PI deflection of the human MP 13. N2 is followed by a positive deflection with two peaks; the first at 150 msec (range 132-173 msec) and the second at 265 msec (range 250-300 msec). This double-peaked configuration of the late positivity was not mentioned in the earlier human studies, but a review of our data shows this to be a frequent finding in human MPs, as depicted in Fig. 1. We have designated these late peaks P2 and P3 :::. The same configuration was found in all 4 monkeys for the discrete wrist extension. When the movement was altered to include both active extension and flexion, the waveform was prolonged and the later components became more complex. The antecedent components of the MP are sharply reduced in amplitude overlying the ipsilateral hemisphere. NI is completely absent from ipsilateral recordings while the N2 component is limited to electrode sites immediately anterior to the central sulcus and reached a maximal amplitude less than 30 o~, of the maximal contralateral N2. P2 is also predominantly contralateral but P3 is symmetrical in distribution over the two hemispheres. The contralateral epidural amplitude distributions of N2, P2 and P3 are depicted as isopotential maps in Fig. 2. Although there is some overlap, the potential distributions differ for each component. The N2 distribution is quite circumscribed with its maximum overlying the hand area of precentral motor cortex. Although N1 was not mapped in detail, its distribution is roughly comparable to that of N2. The P2 distribution overlies both pre- and postcentral cortex including the N2 distribution within its boundaries. P3, in contrast, is more medially distributed and, as previously mentioned, bilaterally symmetrical. Each of the MP components inverted in polarity from surface to subcortical recordings within regions underlying the maxima of its epidural distribution (Fig. 3); N2 is clearly restricted to the hand area of precentral cortex, P2 is generated both in pre- and postcentral cortex, whereas P3 is generated solely within area 5. Although our laminar analyses are not yet complete, the antecedent MP activity inverts in polarity deeply, across laminae 4 and 5, while the P2 and P3 components invert more superficially. This finding appears to support the recent observations of Asanuma and Rosen 1 as to the functional organization of precentral cortex. The morphology and distribution of the monkey MP are in substantial agreement with our earlier studies of the human MP ~3. The precise localization of the N2 component to the precentral motor cortex lends strong support to the conclusion,
* We favor a serial numbering of MP peaks rather than the terminology introduced by Deecke et al.=', since the latter ascribes a functional significance to the individual waves which is not yet supported by empirical evidence. Note that the designation of the long latency component of the MP as P3 does not imply that it is functionally related to the P3 phenomena in sensory evoked potentials.
102
EMG
/~.~___
Fig. 2. Epidural amplitude distributions for the N2, P2 and P3 components of the contralateral MP in one monkey. The isopotential lines represent 90, 80, 65 and 50~ of the maximal baseline to peak voltage of each component.
based upon scalp topography, that the human N2 component is generated exclusively in the precentral gyrus. Similarly, the presence of generators of P2 in both pre- and postcentral cortex confirms our assertion concerning the sources of the comparable human MP component. The finding of bilateral sources in area 5 for the later positive wave (P3) which was distinguished from the earlier positivity in the human studies, is a new discovery. The localization and timing of the gross MP components can be compared to the temporal pattern of single unit activity recorded during voluntary movements in the monkey. Although most of the single unit studies have utilized a stimulus triggered
103 INVERSION NO INVERSION
dura
°ii"
21~MSEC
EMG
Fig. 3. Recording sites which yielded evidence of active response in underlying surface cortex. Loci showing transcortical polarity inversions of the component indicated by the arrows are depicted as solid circles, and placements which revealed only volume conducted activity are indicated by open circles. Composite of recordings from 2 monkeys. Overlapping sites which revealed the same results in both monkeys have been deleted. task rather than self-paced contractions employed here, it is clear that the N2 c o m p o nent o f the MP closely corresponds to the time course o f precentral unit activity and arises from the same cortical sites. Similarly, as recently reported by Schmidt et al. l°, the slow shift, N I , is concurrent with a gradual increase in firing o f some o f the same neurons which participate in the phasic premovement discharge. In the present study we found no evidence o f activity related to m o v e m e n t in frontal granular cortex as described by K u b o t a and Niki 8 in a delayed alternation task. Thus, it appears that the D R L task may involve different mechanisms o f m o v e m e n t initiation than delayed alternation. The pre- and postcentral origins o f P2 raise some questions in relation to the reports by Evarts 3,4 on the timing o f pre- and postcentral units. His studies have disclosed little late spike activity from precentral cortex, and the postcentral unit activity
104 subsided earlier t h a n P2. l h u s , we have identified gross cortical potentials generaied in both the precentral a n d poslcentral region for which there as yet exists no demonstraled c o u n t e r p a r t in single n e u r o n recordings. F u r t h e r m o r e , the precentral distribution ot s o m a t o s e n s o r y evoked potentials, recorded from the monkeys studied here, is tinmed to the a n t e r i o r b a n k of the central fissure (unpublished observations), II appears that the peripheral afferents do not extend as widely as the region involved in the generation of P2 and therefore we speculate that P2 reflects, in part, a central feedback mechanism as was suggested by our earlier results in deafferented monkeys ~ Finally, the late positivity (P3) derives from an area of cortex which has, in llle alert monkey, a distinctive somatosensory input described by Sakata ~'l al. 9. its long latency (over 200 msec after the onset of the movement) and bilateral representation are in c o n f o r m i t y with the timing a n d spatial properties of area 5 n e u r o n s in response to somesthetic inputs. O u r tindings of area 5 activity related to active m o t i o n tends to s u p p o r t the suggestion by Sakata el al. 'a that this region might encode i n f o r m a l i o n on body position. This work was supported by G r a n t GB-35596 from the National Science F o u n d a t i o n , G r a n t MH06723 from N I M H , and G r a n t HD-01799 from N I H .
1 ASANUMA, H., AND ROSEN, I., Functional role of afferent inputs to the monkey motor cortex, Brain Research, 40 (1972) 3 5.
2 DEECKE,L., SCHEID, P., AND KORNHUaER,H. H., Distribution of readiness potential, pre-motion positivity, and motor potential of the human cerebral cortex preceding voluntary finger movements, Exp. Brain Res., 7 (1969) 158-168. 3 EVARTS,E. V., Contrasts between activity of precentral and postcentral neurons of cerebral cortex during movement in the monkey, Brain Research, 40 (1972) 25 31. 4 EVARTS,E. V., Precentral and postcentral cortical activity in association with visually triggered movement, J. Neurophysiol., 37 (1974) 373-381. 5 GERnnANDT,L. K., Govv, W. R., ANDSMITH,D. B., Distribution of the human average movenlent potential, Electroeneeph. olin. Neurophysiol., 34 (1973)461-474. 6 GILDEN, L., VAUGHAN,H. G., JR., AND COSTA, L. D., Summated human EEG potentials associated with voluntary movement, Electroenceph. din. Neurophysiol., 20 (1966) 433-438. 7 KORNHUBER, H. H., ONO DEECKE, L., Hirnpotentialfinderungen bei Willktirbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale, pttiiger.s Areh. ges. PhysioL, 284 (11965) 1-17. 8 KOBOTA,K., AND NIKI, H., Prefrontal cortical unit activity and delayed alternation performance in monkeys, J. Neurophysiol., 34 (1971) 337-347. 9 SAKATA,H., TAKAOKA,Y., KAWARASAKJ,A., AND SHmUTANI,H., Somatosensory properties of neurons in the superior parietal cortex (area 5) of the rhesus monkey, Brain Research, 64 (1973) 85-102. 10 SCHMIDT,E. M., JOST, R. G., AND DAVIS,K. K., Cortical cell discharge patterns in anticipation of a trained movement, Brain Research, 75 (1974) 309-311. I 1 VAUGHAN,n. G., JR., BO,SSOM,J., AND GROSS, E. G., Cortical motor potential in monkeys before and after upper limb deafferentation, Exp. Neurol., 26 (1970) 253-262. 12 VAUGHAN,H. G., JR., COSTA, L. D., (JILDEN, L., AND SCHIMMEL,H., Identification of sensory and motor components of cerebral activity in simple reaction-time tasks, Proc. 73rd Cony. Anwr. P~3,chol. Ass., 1 (1965) 179-t80. 13 VAUGHAN,H. G., JR., COSTA,L. D., AND RITTER,W., Topography of the human motor potential, Electroem'eph, clin. NeurophysioL, 25 (I 968) I- 10.
