- Email: [email protected]
Factors influencing accuracy of operant control of pyramidal tract neurons in monkey
418
Brain Research, 152 (1978) 418-421 © Elsevier/North-Holland Biomedical Press
Factors influencing accuracy of operant control of pyramidal tract neurons in monkey
ALLEN R. WYLER* and KIM J. BURCHIEL Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Wash. 98195 (U.S.A.) (Accepted March 16th, 1978)
This laboratory has recently reported a standardized single neuron operant conditioning paradigm which requires the monkey to change a precentral neuron's firing pattern from phasic to tonic 6. The new operant task is termed Differential Reinforcement of Tonic Patterns (DRTP) and can be equated to a tracking task. The advantage of this paradigm is that the monkey's accuracy of control over each neuron can be quantified and subjected to parametric statistical analysis. Since the accuracy with which the monkey controls a neuron is not dependent upon the neuron's initial firing rate, rate variance, or pattern 6, quantitative comparisons of accuracy of control between defined groups of precentral neurons can be made 7. For example, preliminary data 6 suggested that pyramidal tract neurons (PTNs) were, as a group, more accurately controlled than non-PTNs. It was also suggested 6 that various groups of PTNs were differentially controlled, i.e. neurons responding to passive hand movements were more accurately controlled than those responding to shoulder movements. However, that observation was not quantified. Although it is not known how a monkey may operantly control a precentral neuron, it has been observed that the monkey will often produce highly specific movements which correlate with the neuron's firing. As the monkey gains proficient control of the unit, the movements become progressively refined2,5, s. With the additional data that control can be maintained in the absence of auditory and visual feedback 6 there is a high likelihood that proprioceptive feedback may be essential for the monkey's successful operant performance. Therefore, this new set of experiments explored the relationship between the accuracy of operant PTN control and the neuron's response to peripheral stimulation. Data are from two male Macaca mulatta monkeys. Each was implanted with extracellular recording mounts (right precentral cortex) and pyramidal tract stimulating electrodes using methods previously described 6,8. During computer controlled operant (DRTP) periods, the monkey is reinforced (with applesauce) for the production of consecutive interspike intervals (ISI) within a requisite range termed a target. (In all cases the target was 30-60 msec.) Each 15 sec the (PDP 8/e) computer outputs the * Affiliate, Child Development and Mental Retardation Center, University of Washington.
419 TABLE I Mean (and standard deviation) for preconditioning and DRTP~ errors for 46 PTNs Discrete refers to PTNs activated by one passive peripheral movement whereas diffuse refers to activation by more than one movement although they might involve the same joint. The error score for a neuron is the mean msec/15 sec spent off target during a 5 min preconditioning or operant (DRTP) period. Hence, error is inversely related to accuracy.
Discrete n=18 t=0.88 Diffuse n--28
Preconditioning mean error
DRTPb mean error
8278 ± 3548
2318 ± 784 t--4.38, P<0.001
7821 4- 2997
4764 4- 2329
total time (in msec) the neuron fired off target: that time is termed error. Each 5-min DRTP period is separated by 5-min time-out periods and is numbered sequentially; DRTP1 serves as baseline for each experiment. At the end of each behavioral period the computer determined that 5-min period's mean hits (ISis on target) and error. Since the monkey is reinforced for consecutive hits, the best DRTP (DRTPb) period is defined as that period subsequent to DRTP1 which had the highest mean hits; the mean of the 15 sec errors of DRTPb measures absolute accuracy for that neuron 7. Because there is ambiguity concerning the efferent projections of non-PTNs, only physiologically identified PTNs (antidromic latency from the medullary pyramids less than 1.4 msec) were considered in this report. In addition, all PTNs were required to have: (a) unequivocally isolated, uninjured, negative-positive action potentials; (b) been conditioned through at least 6 DRTP periods; (c) peripheral sensory fields sufficiently mapped to allow accurate localization. The following tests were used to determine each PTN's peripheral sensory field: (a) simple tactile (hair) stimulation; (b) pressure to discrete muscle groups; (c) passive movement of all upper extremity joints. (This obviously excludes evaluation of possible afferents from axial musculature, but such afferents to these cells are very unlikelyl,a,4.) A total of 49 PTNs recorded from right precentral cortex (confirmed post mortem) fulfilled the above criteria. None of these responded to tactile stimulation and 3 could not have peripheral fields mapped. Forty of the 46 responded to joint movement, the remaining 6 to muscle palpation. PTNs were first divided into two groups: discrete units responded to one movement whereas diffuse units responded to more than one movement, including opposing movemevts of the same joint. Eighteen PTNs were determined discrete and 28 diffuse. Their respective mean DRTPb errors were 2318 zk 784, and 4764 -4- 2329, which are significantly different (t = 4.38, P < 0.001, 45 df). The DRTPb mean error for the 3 PTNs without peripheral fields was 5193 ~ 3904, and represents too small a sample for statistical analysis. Since DRTPb error is inversely related to accuracy, the discrete PTNs, as a group, were more accurately controlled than diffuse PTNs. To control for the possibility that discrete units might initially be closer
420 TABLE II
Preconditioning and D R T P b mean errors for P T N s responsive to passive movements o f the contralateral arm joints listed
N o resp onse Shoulder Elbow Wrist Hand
N N N N N
= = ~ = =
3 10 17 8 11
Preconditioning mean error
DRTP~ mean error
7942 8285 7445 9121 8194
5183 4961 3641 3447 2800
dz -4± ~ ~z
3817 2512 3771 3744 3009
~~ dz + :~
3904 3170 1788 1674 1725
to the target range, the preconditioning error scores for the two groups were compared; for the discrete and diffuse PTNs the respective error scores were 8278 4- 3548 and 7821 4- 2997 (t = --0.39, not significant). These values are summarized in Table I. Without correlative E M G data, such as reported by Fetz and Baker 2, no relationship between passive and active movements can be made for these units. The PTNs were then divided on the basis of which joints, when passively moved, evoked a response. Without considering if the response was discrete or diffuse, they were activated as follows: (a) 10 to shoulder; (b) 17 to elbow; (c) 8 to wrist; (d) 11 to hand. The mean preconditioning and DRTPb errors for these groups are shown in Table II. PTNs activated by passive shoulder movement had significantly higher mean DRTPb errors than those responding to hand movements (t -- 1.97, P < 0.05, 19 df). As a group, the elbow-activated units did not differ significantly from hand-activated units (t = 1.23, P < 0.1, 26 df). But separating elbow flexion from extension produced the folowing mean errors: flexion = 3480 4- 1692, extension -- 4180 4- 1735. Though not significantly different, flexion-activated units tend to be more accurately controlled than extension-activated units. The preconditioning errors for all groups are not significantly different. These data confirm our earlier impression that PTNs responsive to distal movements are, as a group, more accurately controlled than those responsive to proximal movements 6. But these data are biased in that all shoulder-activated units were also diffusely responsive and, unless proven otherwise, it may be assumed that a discretely responsive shoulder unit might be as accurately controlled as a discretely responsive hand PTN. But using this logic, one could then make the prediction that PTNs responsive to discrete hand movements would be more accurately controlled than those responsive to diffuse hand movements. This, in fact, does not prove true in our sample. For example, the most precisely controlled neuron we have studied was a diffuse unit. It had a mean DRTPb error of 847 msec/15 sec and was responsive to flexion and extension of the second and third digits of the contralateral hand. In addition, these data deal only with fast PTNs and may not be applicable to either slow PTNs or nonPTNs in precentral cortex. The present data provides two major findings: (1) fast PTNs responsive to discrete movements are more accurately controlled than those responsive to diffuse movements,
421 a n d (2) the m o n k e y ' s o p e r a n t accuracy i m p r o v e s (in a r m - r e l a t e d units) the m o r e distal the P T N s ' p e r i p h e r a l field. A l t h o u g h this does n o t elucidate the m e t h o d by which the m o n k e y o p e r a n t l y c o n t r o l s a P T N , it suggests t h a t the accuracy o f such c o n t r o l is s o m e w h a t d e p e n d e n t u p o n the specificity o f p e r i p h e r a l to central f e e d b a c k loops 1,a,4. This research was s u p p o r t e d b y N I H R e s e a r c h Gr~/nts NS-04053 a n d T e a c h e r I n v e s t i g a t o r A w a r d ( A R W ) NS-195-01A2 a w a r d e d by the N a t i o n a l I n s t i t u t e o f N e u r o l o g i c a l a n d C o m m u n i c a t i v e Disorders, P H S / D H E W .
1 Asanuma, H. and Rosen, I., Topographical organization of cortical efferent zones projecting to distal forelimb in the monkey, Exp. Brain Res., 14 (1972) 243-256. 2 Fetz, E. E. and Baker, M. A., Operantly conditioned patterns of precentral unit activity and correlated responses in adjacent cells and contralateral muscles, J. Neurophysiol., 36 (1973) 179-204. 3 Lemon, R. N. and Porter, R., Afferent input to movement-related precentral neurones in conscious monkeys, Proc. roy. Soc. B, 194 (1975) 313-339. 4 Lemon, R. N., Hanby, J. A. and Porter, R., Relationship between the activity of precentral neurones during active and passive movements in conscious monkeys, Proc. roy. Soc. B, 194 (1976) 341-373. 5 Schmidt, E. M., Back, M. J., Mclntosh, J. S. and Thomas, J. S., Operant conditioning of firing patterns in monkey cortical neurons, Exp. Neurol., 54 (1977) 467477. 6 Wyler, A. R. and Finch, C. A., Operant conditioning of tonic firing patterns from precentral neurons in monkey neocortex, Brain Research, 146 (1978) 51-69. 7 Wyler, A. R., Finch, C. A. and Burchiel, K. J., Epileptic and normal neurons in monkey neocortex • a quantitative study of degree of control, Brain Research, in press. 8 Wyler, A. R. and Fetz, E. E., Behavioral control of firing patterns of normal and abnormal neurons in chronic epileptic cortex, Exp. Neurol., 42 (1974) 448~,64.
Brain Research, 152 (1978) 418-421 © Elsevier/North-Holland Biomedical Press
Factors influencing accuracy of operant control of pyramidal tract neurons in monkey
ALLEN R. WYLER* and KIM J. BURCHIEL Department of Neurological Surgery, University of Washington School of Medicine, Seattle, Wash. 98195 (U.S.A.) (Accepted March 16th, 1978)
This laboratory has recently reported a standardized single neuron operant conditioning paradigm which requires the monkey to change a precentral neuron's firing pattern from phasic to tonic 6. The new operant task is termed Differential Reinforcement of Tonic Patterns (DRTP) and can be equated to a tracking task. The advantage of this paradigm is that the monkey's accuracy of control over each neuron can be quantified and subjected to parametric statistical analysis. Since the accuracy with which the monkey controls a neuron is not dependent upon the neuron's initial firing rate, rate variance, or pattern 6, quantitative comparisons of accuracy of control between defined groups of precentral neurons can be made 7. For example, preliminary data 6 suggested that pyramidal tract neurons (PTNs) were, as a group, more accurately controlled than non-PTNs. It was also suggested 6 that various groups of PTNs were differentially controlled, i.e. neurons responding to passive hand movements were more accurately controlled than those responding to shoulder movements. However, that observation was not quantified. Although it is not known how a monkey may operantly control a precentral neuron, it has been observed that the monkey will often produce highly specific movements which correlate with the neuron's firing. As the monkey gains proficient control of the unit, the movements become progressively refined2,5, s. With the additional data that control can be maintained in the absence of auditory and visual feedback 6 there is a high likelihood that proprioceptive feedback may be essential for the monkey's successful operant performance. Therefore, this new set of experiments explored the relationship between the accuracy of operant PTN control and the neuron's response to peripheral stimulation. Data are from two male Macaca mulatta monkeys. Each was implanted with extracellular recording mounts (right precentral cortex) and pyramidal tract stimulating electrodes using methods previously described 6,8. During computer controlled operant (DRTP) periods, the monkey is reinforced (with applesauce) for the production of consecutive interspike intervals (ISI) within a requisite range termed a target. (In all cases the target was 30-60 msec.) Each 15 sec the (PDP 8/e) computer outputs the * Affiliate, Child Development and Mental Retardation Center, University of Washington.
419 TABLE I Mean (and standard deviation) for preconditioning and DRTP~ errors for 46 PTNs Discrete refers to PTNs activated by one passive peripheral movement whereas diffuse refers to activation by more than one movement although they might involve the same joint. The error score for a neuron is the mean msec/15 sec spent off target during a 5 min preconditioning or operant (DRTP) period. Hence, error is inversely related to accuracy.
Discrete n=18 t=0.88 Diffuse n--28
Preconditioning mean error
DRTPb mean error
8278 ± 3548
2318 ± 784 t--4.38, P<0.001
7821 4- 2997
4764 4- 2329
total time (in msec) the neuron fired off target: that time is termed error. Each 5-min DRTP period is separated by 5-min time-out periods and is numbered sequentially; DRTP1 serves as baseline for each experiment. At the end of each behavioral period the computer determined that 5-min period's mean hits (ISis on target) and error. Since the monkey is reinforced for consecutive hits, the best DRTP (DRTPb) period is defined as that period subsequent to DRTP1 which had the highest mean hits; the mean of the 15 sec errors of DRTPb measures absolute accuracy for that neuron 7. Because there is ambiguity concerning the efferent projections of non-PTNs, only physiologically identified PTNs (antidromic latency from the medullary pyramids less than 1.4 msec) were considered in this report. In addition, all PTNs were required to have: (a) unequivocally isolated, uninjured, negative-positive action potentials; (b) been conditioned through at least 6 DRTP periods; (c) peripheral sensory fields sufficiently mapped to allow accurate localization. The following tests were used to determine each PTN's peripheral sensory field: (a) simple tactile (hair) stimulation; (b) pressure to discrete muscle groups; (c) passive movement of all upper extremity joints. (This obviously excludes evaluation of possible afferents from axial musculature, but such afferents to these cells are very unlikelyl,a,4.) A total of 49 PTNs recorded from right precentral cortex (confirmed post mortem) fulfilled the above criteria. None of these responded to tactile stimulation and 3 could not have peripheral fields mapped. Forty of the 46 responded to joint movement, the remaining 6 to muscle palpation. PTNs were first divided into two groups: discrete units responded to one movement whereas diffuse units responded to more than one movement, including opposing movemevts of the same joint. Eighteen PTNs were determined discrete and 28 diffuse. Their respective mean DRTPb errors were 2318 zk 784, and 4764 -4- 2329, which are significantly different (t = 4.38, P < 0.001, 45 df). The DRTPb mean error for the 3 PTNs without peripheral fields was 5193 ~ 3904, and represents too small a sample for statistical analysis. Since DRTPb error is inversely related to accuracy, the discrete PTNs, as a group, were more accurately controlled than diffuse PTNs. To control for the possibility that discrete units might initially be closer
420 TABLE II
Preconditioning and D R T P b mean errors for P T N s responsive to passive movements o f the contralateral arm joints listed
N o resp onse Shoulder Elbow Wrist Hand
N N N N N
= = ~ = =
3 10 17 8 11
Preconditioning mean error
DRTP~ mean error
7942 8285 7445 9121 8194
5183 4961 3641 3447 2800
dz -4± ~ ~z
3817 2512 3771 3744 3009
~~ dz + :~
3904 3170 1788 1674 1725
to the target range, the preconditioning error scores for the two groups were compared; for the discrete and diffuse PTNs the respective error scores were 8278 4- 3548 and 7821 4- 2997 (t = --0.39, not significant). These values are summarized in Table I. Without correlative E M G data, such as reported by Fetz and Baker 2, no relationship between passive and active movements can be made for these units. The PTNs were then divided on the basis of which joints, when passively moved, evoked a response. Without considering if the response was discrete or diffuse, they were activated as follows: (a) 10 to shoulder; (b) 17 to elbow; (c) 8 to wrist; (d) 11 to hand. The mean preconditioning and DRTPb errors for these groups are shown in Table II. PTNs activated by passive shoulder movement had significantly higher mean DRTPb errors than those responding to hand movements (t -- 1.97, P < 0.05, 19 df). As a group, the elbow-activated units did not differ significantly from hand-activated units (t = 1.23, P < 0.1, 26 df). But separating elbow flexion from extension produced the folowing mean errors: flexion = 3480 4- 1692, extension -- 4180 4- 1735. Though not significantly different, flexion-activated units tend to be more accurately controlled than extension-activated units. The preconditioning errors for all groups are not significantly different. These data confirm our earlier impression that PTNs responsive to distal movements are, as a group, more accurately controlled than those responsive to proximal movements 6. But these data are biased in that all shoulder-activated units were also diffusely responsive and, unless proven otherwise, it may be assumed that a discretely responsive shoulder unit might be as accurately controlled as a discretely responsive hand PTN. But using this logic, one could then make the prediction that PTNs responsive to discrete hand movements would be more accurately controlled than those responsive to diffuse hand movements. This, in fact, does not prove true in our sample. For example, the most precisely controlled neuron we have studied was a diffuse unit. It had a mean DRTPb error of 847 msec/15 sec and was responsive to flexion and extension of the second and third digits of the contralateral hand. In addition, these data deal only with fast PTNs and may not be applicable to either slow PTNs or nonPTNs in precentral cortex. The present data provides two major findings: (1) fast PTNs responsive to discrete movements are more accurately controlled than those responsive to diffuse movements,
421 a n d (2) the m o n k e y ' s o p e r a n t accuracy i m p r o v e s (in a r m - r e l a t e d units) the m o r e distal the P T N s ' p e r i p h e r a l field. A l t h o u g h this does n o t elucidate the m e t h o d by which the m o n k e y o p e r a n t l y c o n t r o l s a P T N , it suggests t h a t the accuracy o f such c o n t r o l is s o m e w h a t d e p e n d e n t u p o n the specificity o f p e r i p h e r a l to central f e e d b a c k loops 1,a,4. This research was s u p p o r t e d b y N I H R e s e a r c h Gr~/nts NS-04053 a n d T e a c h e r I n v e s t i g a t o r A w a r d ( A R W ) NS-195-01A2 a w a r d e d by the N a t i o n a l I n s t i t u t e o f N e u r o l o g i c a l a n d C o m m u n i c a t i v e Disorders, P H S / D H E W .
1 Asanuma, H. and Rosen, I., Topographical organization of cortical efferent zones projecting to distal forelimb in the monkey, Exp. Brain Res., 14 (1972) 243-256. 2 Fetz, E. E. and Baker, M. A., Operantly conditioned patterns of precentral unit activity and correlated responses in adjacent cells and contralateral muscles, J. Neurophysiol., 36 (1973) 179-204. 3 Lemon, R. N. and Porter, R., Afferent input to movement-related precentral neurones in conscious monkeys, Proc. roy. Soc. B, 194 (1975) 313-339. 4 Lemon, R. N., Hanby, J. A. and Porter, R., Relationship between the activity of precentral neurones during active and passive movements in conscious monkeys, Proc. roy. Soc. B, 194 (1976) 341-373. 5 Schmidt, E. M., Back, M. J., Mclntosh, J. S. and Thomas, J. S., Operant conditioning of firing patterns in monkey cortical neurons, Exp. Neurol., 54 (1977) 467477. 6 Wyler, A. R. and Finch, C. A., Operant conditioning of tonic firing patterns from precentral neurons in monkey neocortex, Brain Research, 146 (1978) 51-69. 7 Wyler, A. R., Finch, C. A. and Burchiel, K. J., Epileptic and normal neurons in monkey neocortex • a quantitative study of degree of control, Brain Research, in press. 8 Wyler, A. R. and Fetz, E. E., Behavioral control of firing patterns of normal and abnormal neurons in chronic epileptic cortex, Exp. Neurol., 42 (1974) 448~,64.