Brain Research, 116 (1976) 145-149
145
© Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Autoradiographic demonstration of a projection from prefrontal association cortex to the superior collicuIus in the rhesus monkey
PATRICIA S. GOLDMAN and WALLE J. H. NAUTA National Institute of Mental Health, Bethesda, Md. 20014 and Massachusetts Institute of Technology, Cambridge, Mass. 02139 (U.S.A.)
(Accepted July 14th, 1976)
Recent electrophysiological and behavioral studies in the primateS,6,17,20, 21 have indicated that the superior colliculus may be involved in mediating a monkey's readiness to respond to visual targets in space but the anatomical connections subserving a tectal mechanism of visual attention are not well understood. Goldberg and Wurtz 6 have argued that intracollicular connections do not seem to provide an adequate neural basis for the visuomotor integrative properties exhibited by tectal units and have hypothesized that extravisual afferents to the colliculus, possible of cortical origin, may provide a central mechanism for regulating movements of the eye. In the course of a wider study on the development of cortical efferents in the rhesus monkey 7,s, we obtained evidence for a substantial projection from the cortex in the dorsal bank of the principal sulcus to the intermediate and deeper layers of the superior colliculus. This finding is of interest because the region in question is the prefrontal association cortex, anatomicallyl,7,s,ls, 19 and functionally4,9,10 distinct from the frontal eye field which until now has been the only frontal region considered as a likely source of corticotectal fibers 14. Rhesus monkeys of different ages received injections of 20-40/~Ci of a mixture of equal parts tritiated leucine and tritiated proline into the middle third of the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex. A terminal distribution of radioactive label in the superior colliculus was found only in cases of label injection into the principalsulcus cortex. It is remarkable that the label accumulation in the colliculus was very much denser in the youngest monkeys than in the older animals. However, even in an adult monkey the corticotectal-fiber labeling, to be described below, was found to be quite distinct, and the sole reason for documenting only the findings in a 4-day-old animal is that the denser labeling made this case particularly suitable for low-power macrophotography. Incidentally, in these same cases similar quantitative age-related differences in label transport were observed in certain corticocortical and corticostriatal connections; for a discussion of some factors possibly underlying these differences reference is made to the two pertinent publicationsT, 8. The present description is based upon the case of a 4-day-old monkey in which
146 30 #Ci of the labeled amino acids had been injected into the dorsal bank of the principal sulcus in a single penetration; the animal had been sacrificed 7 days postoperatively. Further details as to surgical and histological procedures are reported elsewhere v. The injection site was confined to the middle third of the length of the dorsal bank of the principal sulcus, extending approximately half-way from the rim to the fundus of the sulcus (Fig. 1). The regional specificity of the cortical territory directly labeled in this case is corroborated by the distribution of labeled cortico-thalamic projections. Heavy labeling marks the parvocellular portion of the mediodorsal nucleus, the origin of the thalamocortical fibers to the dorsal prefrontal cortex 1. Label has not been transported to either the pars magnocellularis or the pars multiformis, subdivisions of the mediodorsal nucleus, which project preferentially to, respectively, the orbital surface of the frontal lobe and the transitional granular cortex in the bend of the arcuate sulcus. This latter region roughly corresponds to the frontal eye field. In sections at rostral mesencephalic levels, dense concentrations of grains appear in the middle portion of the cerebral peduncle and in the medial lemniscus on the side of the injection. These are interpreted as labeled axons leaving the cerebral peduncle and penetrating the medial lemniscus, eventually to enter and terminate in the superior colliculus. The rostral one-third of the superior colliculus is free of radioactive label, but in sections behind that level grains begin to appear near the tectal midline. In successively more caudal sections this labeling rapidly increases in density and spreads laterally over the deep layers of the caudomedial quadrant, to some extent and in decreasing density also into more lateral parts of the colliculus. Within the caudomcdial quadrant all collicular layers below the stratum griseum medium are densely labeled: lesser
Fig. 1. Diagrammatic illustration of the injection site in the dorsal bank along the middle third of the principal sulcus on a standard lateral view of the monkey brain, and selected cross sections through the injected area.
147 grain concentrations mark the deeper half of the stratum griseum medium, but labeling is at or near background level in the stratum opticum and throughout the stratum griseum superficiale (Fig. 2). The distribution of this corticotectal projection is not entirely uniform, but instead shows a configuration in which areas of high grain-concentration surround areas with lower concentrations of grain (Fig. 2). This uneven labeling is somewhat reminiscent of the pattern of 'puffs and holes' recently observed in the distribution of retinotecta111, la and nigrotectal 1~ fibers in the more superficial layers of the colliculus, but it is considerably less regular than the latter. Immediately contiguous with the dense grain accumulation in the deep collicular layers, labeling appears in a dorsolateral region of the central gray substance. Although the grain concentration in this region is well below that of the colliculus, it is high enough to be visible in the low-power photograph of Fig. 2. N o t shown by this illustration are some further labeled areas in dorsal regions of the pontine nuclei.
Fig. 2. Dark-field autoradiogram illustrating radioactivity in the intermediate and deep layers of the superior colliculus ipsilateral to the injected cortex. Note small territories in which grain concentration is below that of surrounding areas. Labeled fibers may be seen ascending from the cerebral peduncle along the lateral margin of the brain stem, terminating also in the central gray substance. Light areas appearing beneath the aqueduct are fiber bundles which often appear luminescent in autoradiograms. In this instance, these bundles are free of radioactive label. Magnification, × 25.
148 The present demonstration of a prominent connection from the middle third region of the principal sulcus to the intermediate and deep strata of the superior colliculus extends and amplifies previous observations in fiber-degeneration studies. In such studies Kuypers and Lawrence 15 and Astruc 2 have shown that lesions of the anterior bank of the arcuate sulcus, roughly coextensive with the frontal eye field, result in fiber degeneration in approximately the same layers of the colliculus that were labeled in the present study. Moreover, the course followed by these fibers in transit to the colliculus was similar to that of the labeled fibers traced from the principalsulcus cortex in the present study. In addition to the projection from the frontal eye field to the superior colliculus, Kuypers and Lawrence 15 reported evidence of a corticotectal projection originating at or near the frontal pole. Unfortunately, this evidence was not documented in sufficient detail to determine whether and to what extent the lesions in question may have coincided with the injection field of the present study. Perhaps because Kuypers and Lawrence's findings in cases of frontopolar lesion were not emphasized, the presence of a connection between prefrontal association cortex and the superior colliculus appears to have been largely overlooked in the study of extravisual cortical influence on the functions of the colliculus. The present autoradiographic evidence of a prominent input to the colliculus from a prefrontal region outside the recognized limits of the frontal eye field may serve to bring the prefrontotectal connection into wider recognition. Considered together, the findings in autoradiographic and fiber-degeneration studies indicate the possibility that a considerable portion of the dorsolateral-convexity cortex projects to the superior colliculus, but it is clear that a more systematic investigation is needed to determine the limits of the region from which prefrontotectal fibers originate. Our present negative findings in cases of label-injection in the posterior orbital cortex would appear to rule out this ventral region of the prefrontal cortex as a major source of corticotectal fibers. Previous attempts to localize an extravisual cortical mechanism for the initiation of eye movements have focused on the frontal eye field. Bizzi and Schillera and Mohler, Goldberg and Wurtz 16, recording from single units in the frontal eye field of unanesthetized monkeys during eye movement, found that, in general, eye movements of various types precede rather than follow unit activity in area 8. These observations at best provide no evidence for an effector function of the frontal eye field in the initiation of eye movements. On the basis of the present results, the possibility that the more rostrally located cortex lining and bordering the principal sulcus might serve such a function needs to be investigated. It should be noted in this context that the principal-sulcus cortex projects to the frontal eye field as well as to the colliculus 7, and thus could also affect movement-related unit activity in the frontal eye fielda,16. In addition to providing further evidence of frontotectal connections, the results of the present study may be of some special interest in relation to the functions of the principal-sulcus cortex. This circumscript region of the frontal association cortex is highly specialized in both its functions 4,9,10 and to some extent also its anatomical connections7,8,18. Lesions confined to the cortex of the principal sulcus, or even to its middle one-third alone, selectively impair the monkey's performance in those forms of the delayed-response test in which correct spatial orientation is a crucial require-
149 ment, while leaving intact the capacity to perform a wide variety of equally difficult n o n s p a t i a l tasksg, 10. Since the superior colliculus appears to c o n t a i n a n e u r a l m e c h a n ism of essential i m p o r t a n c e in localizing a n d tracking targets in space, the prefrontotectal c o n n e c t i o n here d e m o n s t r a t e d would seem to offer a possible e x p l a n a t i o n for the loss of spatial abilities observed in m o n k e y s bilaterally deprived of the cortex lining the principal sulcus. Supported by Public Health Service G r a n t s N B 06542 a n d P01 NS 12336 a n d by i n t r a m u r a l research funds of the N a t i o n a l Institute o f M e n t a l Health.
1 Akert, K., Comparative anatomy of frontal cortex and thalamo-frontal connections. In J. M. Warren and K. Akert (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, New York, 1964, pp. 372-396. 2 Astruc, J., Corticofugal connections of area 8 (frontal eye field) in Macacamulatta, Brain Research, 33 (1971) 241-256. 3 Bizzi, E. and Schiller, P. H., Single unit activity in the frontal eye fields of unanesthetized monkeys during eye and head movements, Exp. Brain Res., 10 (1970) 151-158. 4 Butters, N., Pandya, D., Stein, D. and Rosen, J., A search for the spatial engram within the frontal lobes of monkeys, Acta Neurobiol. Exp., 32 (1972) 305-329. 5 Goldberg, M. E. and Wurtz, R. H., Activity of superior colliculus in behaving monkey. I. Visual receptive fields of single neurons, J. NeurophysioL, 35 (1972) 542-559. 6 Goldberg, M.E. and Wurtz, R. H., Activity of superior colliculus in behaving monkey. II. Effect of attention on neuronal responses, J. NeurophysioL, 35 (1972) 560-574. 7 Goldman, P.S. and Nauta, W. J. H., Columnar distribution of cortico-cortical fibers in the frontal association, limbic, and motor cortex of the developing rhesus monkey, Brain Research, in press. 8 Goldman, P. S., and Nauta, W. J. H., An intricately patterned prefronto-caudate projection in the rhesus monkey, J. Comp. Neurol., in press. 9 Goldman, P. S. and Rosvold, H. E., Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey, Exp. Neurol., 27 (1970) 291-304. 10 Goldman, P. S., Rosvold, H. E., Vest, B. and Galkin, T. W., Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey, J. comp. physiol. Psychol., 77 (1971) 212-220. 11 Graybiel, A. M., Anatomical organization of retinotectal afferents in the cat: an autoradiographic study, Brain Research, 96 (1975) 1-24. 12 Graybiel, A. M. and Sciascia, T.R., Origin and distribution of nigrotectal fibers in the cat, Neuroscience Abstr., 1 (1975) 174. 13 Hubel, D. H., LeVay, S. and Wiesel, T. N., Mode of termination of retinotectal fibers in macaque monkey: an autoradiographic study, Brain Research, 96 (1975) 2520. 14 Ingle, D. and Sprague, J. M., Sensorimotor function of the midbrain tectum, Neurosci. Res. Progr. Bull., 13 (1975) 169-288. 15 Kuypers, H. G. J. M. and Lawrence, D. G., Cortical projections to the red nucleus and the brain stem in the rhesus monkey, Brain Research, 4 (1967) 151-188. 16 Mohler, C. W., Goldberg, M. E. and Wurtz, R. H., Visual receptive fields of frontal eye field neurons, Brain Research, 61 (1973) 385-389. 17 Mohler, C. W. and Wurtz, R. H., Organization of monkey superior colliculus: intermediate layer cells discharging before eye movements, J. NeurophysioL, in press. 18 Pandya, D. N., Dye, P. and Butters, N., Efferent cortico-cortical projections of the prefrontal cortex in the rhesus monkey, Brain Research, 31 (1971) 35-46. 19 Pandya, D. N. and Kuypers, H. G. J. M., Cortico-cortical connections in the rhesus monkey, Brain Research, 13 (1969) 13-36. 20 Wurtz, R. H. and Goldberg, M.E., Activity of superior colliculus in behaving monkey. IlL Cells discharging before eye movements, J. NeurophysioL, 35 (1972) 575-586. 21 Wurtz, R.H. and Goldberg, M.E., Activity of superior colliculus in behaving monkey. IV. Effects of lesions on eye movements, J. Neurophysiol., 35 (1972) 587-596.
145
© Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Autoradiographic demonstration of a projection from prefrontal association cortex to the superior collicuIus in the rhesus monkey
PATRICIA S. GOLDMAN and WALLE J. H. NAUTA National Institute of Mental Health, Bethesda, Md. 20014 and Massachusetts Institute of Technology, Cambridge, Mass. 02139 (U.S.A.)
(Accepted July 14th, 1976)
Recent electrophysiological and behavioral studies in the primateS,6,17,20, 21 have indicated that the superior colliculus may be involved in mediating a monkey's readiness to respond to visual targets in space but the anatomical connections subserving a tectal mechanism of visual attention are not well understood. Goldberg and Wurtz 6 have argued that intracollicular connections do not seem to provide an adequate neural basis for the visuomotor integrative properties exhibited by tectal units and have hypothesized that extravisual afferents to the colliculus, possible of cortical origin, may provide a central mechanism for regulating movements of the eye. In the course of a wider study on the development of cortical efferents in the rhesus monkey 7,s, we obtained evidence for a substantial projection from the cortex in the dorsal bank of the principal sulcus to the intermediate and deeper layers of the superior colliculus. This finding is of interest because the region in question is the prefrontal association cortex, anatomicallyl,7,s,ls, 19 and functionally4,9,10 distinct from the frontal eye field which until now has been the only frontal region considered as a likely source of corticotectal fibers 14. Rhesus monkeys of different ages received injections of 20-40/~Ci of a mixture of equal parts tritiated leucine and tritiated proline into the middle third of the dorsal bank of the principal sulcus, the posterior part of the medial orbital gyrus, or the hand and arm area of the primary motor cortex. A terminal distribution of radioactive label in the superior colliculus was found only in cases of label injection into the principalsulcus cortex. It is remarkable that the label accumulation in the colliculus was very much denser in the youngest monkeys than in the older animals. However, even in an adult monkey the corticotectal-fiber labeling, to be described below, was found to be quite distinct, and the sole reason for documenting only the findings in a 4-day-old animal is that the denser labeling made this case particularly suitable for low-power macrophotography. Incidentally, in these same cases similar quantitative age-related differences in label transport were observed in certain corticocortical and corticostriatal connections; for a discussion of some factors possibly underlying these differences reference is made to the two pertinent publicationsT, 8. The present description is based upon the case of a 4-day-old monkey in which
146 30 #Ci of the labeled amino acids had been injected into the dorsal bank of the principal sulcus in a single penetration; the animal had been sacrificed 7 days postoperatively. Further details as to surgical and histological procedures are reported elsewhere v. The injection site was confined to the middle third of the length of the dorsal bank of the principal sulcus, extending approximately half-way from the rim to the fundus of the sulcus (Fig. 1). The regional specificity of the cortical territory directly labeled in this case is corroborated by the distribution of labeled cortico-thalamic projections. Heavy labeling marks the parvocellular portion of the mediodorsal nucleus, the origin of the thalamocortical fibers to the dorsal prefrontal cortex 1. Label has not been transported to either the pars magnocellularis or the pars multiformis, subdivisions of the mediodorsal nucleus, which project preferentially to, respectively, the orbital surface of the frontal lobe and the transitional granular cortex in the bend of the arcuate sulcus. This latter region roughly corresponds to the frontal eye field. In sections at rostral mesencephalic levels, dense concentrations of grains appear in the middle portion of the cerebral peduncle and in the medial lemniscus on the side of the injection. These are interpreted as labeled axons leaving the cerebral peduncle and penetrating the medial lemniscus, eventually to enter and terminate in the superior colliculus. The rostral one-third of the superior colliculus is free of radioactive label, but in sections behind that level grains begin to appear near the tectal midline. In successively more caudal sections this labeling rapidly increases in density and spreads laterally over the deep layers of the caudomedial quadrant, to some extent and in decreasing density also into more lateral parts of the colliculus. Within the caudomcdial quadrant all collicular layers below the stratum griseum medium are densely labeled: lesser
Fig. 1. Diagrammatic illustration of the injection site in the dorsal bank along the middle third of the principal sulcus on a standard lateral view of the monkey brain, and selected cross sections through the injected area.
147 grain concentrations mark the deeper half of the stratum griseum medium, but labeling is at or near background level in the stratum opticum and throughout the stratum griseum superficiale (Fig. 2). The distribution of this corticotectal projection is not entirely uniform, but instead shows a configuration in which areas of high grain-concentration surround areas with lower concentrations of grain (Fig. 2). This uneven labeling is somewhat reminiscent of the pattern of 'puffs and holes' recently observed in the distribution of retinotecta111, la and nigrotectal 1~ fibers in the more superficial layers of the colliculus, but it is considerably less regular than the latter. Immediately contiguous with the dense grain accumulation in the deep collicular layers, labeling appears in a dorsolateral region of the central gray substance. Although the grain concentration in this region is well below that of the colliculus, it is high enough to be visible in the low-power photograph of Fig. 2. N o t shown by this illustration are some further labeled areas in dorsal regions of the pontine nuclei.
Fig. 2. Dark-field autoradiogram illustrating radioactivity in the intermediate and deep layers of the superior colliculus ipsilateral to the injected cortex. Note small territories in which grain concentration is below that of surrounding areas. Labeled fibers may be seen ascending from the cerebral peduncle along the lateral margin of the brain stem, terminating also in the central gray substance. Light areas appearing beneath the aqueduct are fiber bundles which often appear luminescent in autoradiograms. In this instance, these bundles are free of radioactive label. Magnification, × 25.
148 The present demonstration of a prominent connection from the middle third region of the principal sulcus to the intermediate and deep strata of the superior colliculus extends and amplifies previous observations in fiber-degeneration studies. In such studies Kuypers and Lawrence 15 and Astruc 2 have shown that lesions of the anterior bank of the arcuate sulcus, roughly coextensive with the frontal eye field, result in fiber degeneration in approximately the same layers of the colliculus that were labeled in the present study. Moreover, the course followed by these fibers in transit to the colliculus was similar to that of the labeled fibers traced from the principalsulcus cortex in the present study. In addition to the projection from the frontal eye field to the superior colliculus, Kuypers and Lawrence 15 reported evidence of a corticotectal projection originating at or near the frontal pole. Unfortunately, this evidence was not documented in sufficient detail to determine whether and to what extent the lesions in question may have coincided with the injection field of the present study. Perhaps because Kuypers and Lawrence's findings in cases of frontopolar lesion were not emphasized, the presence of a connection between prefrontal association cortex and the superior colliculus appears to have been largely overlooked in the study of extravisual cortical influence on the functions of the colliculus. The present autoradiographic evidence of a prominent input to the colliculus from a prefrontal region outside the recognized limits of the frontal eye field may serve to bring the prefrontotectal connection into wider recognition. Considered together, the findings in autoradiographic and fiber-degeneration studies indicate the possibility that a considerable portion of the dorsolateral-convexity cortex projects to the superior colliculus, but it is clear that a more systematic investigation is needed to determine the limits of the region from which prefrontotectal fibers originate. Our present negative findings in cases of label-injection in the posterior orbital cortex would appear to rule out this ventral region of the prefrontal cortex as a major source of corticotectal fibers. Previous attempts to localize an extravisual cortical mechanism for the initiation of eye movements have focused on the frontal eye field. Bizzi and Schillera and Mohler, Goldberg and Wurtz 16, recording from single units in the frontal eye field of unanesthetized monkeys during eye movement, found that, in general, eye movements of various types precede rather than follow unit activity in area 8. These observations at best provide no evidence for an effector function of the frontal eye field in the initiation of eye movements. On the basis of the present results, the possibility that the more rostrally located cortex lining and bordering the principal sulcus might serve such a function needs to be investigated. It should be noted in this context that the principal-sulcus cortex projects to the frontal eye field as well as to the colliculus 7, and thus could also affect movement-related unit activity in the frontal eye fielda,16. In addition to providing further evidence of frontotectal connections, the results of the present study may be of some special interest in relation to the functions of the principal-sulcus cortex. This circumscript region of the frontal association cortex is highly specialized in both its functions 4,9,10 and to some extent also its anatomical connections7,8,18. Lesions confined to the cortex of the principal sulcus, or even to its middle one-third alone, selectively impair the monkey's performance in those forms of the delayed-response test in which correct spatial orientation is a crucial require-
149 ment, while leaving intact the capacity to perform a wide variety of equally difficult n o n s p a t i a l tasksg, 10. Since the superior colliculus appears to c o n t a i n a n e u r a l m e c h a n ism of essential i m p o r t a n c e in localizing a n d tracking targets in space, the prefrontotectal c o n n e c t i o n here d e m o n s t r a t e d would seem to offer a possible e x p l a n a t i o n for the loss of spatial abilities observed in m o n k e y s bilaterally deprived of the cortex lining the principal sulcus. Supported by Public Health Service G r a n t s N B 06542 a n d P01 NS 12336 a n d by i n t r a m u r a l research funds of the N a t i o n a l Institute o f M e n t a l Health.
1 Akert, K., Comparative anatomy of frontal cortex and thalamo-frontal connections. In J. M. Warren and K. Akert (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, New York, 1964, pp. 372-396. 2 Astruc, J., Corticofugal connections of area 8 (frontal eye field) in Macacamulatta, Brain Research, 33 (1971) 241-256. 3 Bizzi, E. and Schiller, P. H., Single unit activity in the frontal eye fields of unanesthetized monkeys during eye and head movements, Exp. Brain Res., 10 (1970) 151-158. 4 Butters, N., Pandya, D., Stein, D. and Rosen, J., A search for the spatial engram within the frontal lobes of monkeys, Acta Neurobiol. Exp., 32 (1972) 305-329. 5 Goldberg, M. E. and Wurtz, R. H., Activity of superior colliculus in behaving monkey. I. Visual receptive fields of single neurons, J. NeurophysioL, 35 (1972) 542-559. 6 Goldberg, M.E. and Wurtz, R. H., Activity of superior colliculus in behaving monkey. II. Effect of attention on neuronal responses, J. NeurophysioL, 35 (1972) 560-574. 7 Goldman, P.S. and Nauta, W. J. H., Columnar distribution of cortico-cortical fibers in the frontal association, limbic, and motor cortex of the developing rhesus monkey, Brain Research, in press. 8 Goldman, P. S., and Nauta, W. J. H., An intricately patterned prefronto-caudate projection in the rhesus monkey, J. Comp. Neurol., in press. 9 Goldman, P. S. and Rosvold, H. E., Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey, Exp. Neurol., 27 (1970) 291-304. 10 Goldman, P. S., Rosvold, H. E., Vest, B. and Galkin, T. W., Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey, J. comp. physiol. Psychol., 77 (1971) 212-220. 11 Graybiel, A. M., Anatomical organization of retinotectal afferents in the cat: an autoradiographic study, Brain Research, 96 (1975) 1-24. 12 Graybiel, A. M. and Sciascia, T.R., Origin and distribution of nigrotectal fibers in the cat, Neuroscience Abstr., 1 (1975) 174. 13 Hubel, D. H., LeVay, S. and Wiesel, T. N., Mode of termination of retinotectal fibers in macaque monkey: an autoradiographic study, Brain Research, 96 (1975) 2520. 14 Ingle, D. and Sprague, J. M., Sensorimotor function of the midbrain tectum, Neurosci. Res. Progr. Bull., 13 (1975) 169-288. 15 Kuypers, H. G. J. M. and Lawrence, D. G., Cortical projections to the red nucleus and the brain stem in the rhesus monkey, Brain Research, 4 (1967) 151-188. 16 Mohler, C. W., Goldberg, M. E. and Wurtz, R. H., Visual receptive fields of frontal eye field neurons, Brain Research, 61 (1973) 385-389. 17 Mohler, C. W. and Wurtz, R. H., Organization of monkey superior colliculus: intermediate layer cells discharging before eye movements, J. NeurophysioL, in press. 18 Pandya, D. N., Dye, P. and Butters, N., Efferent cortico-cortical projections of the prefrontal cortex in the rhesus monkey, Brain Research, 31 (1971) 35-46. 19 Pandya, D. N. and Kuypers, H. G. J. M., Cortico-cortical connections in the rhesus monkey, Brain Research, 13 (1969) 13-36. 20 Wurtz, R. H. and Goldberg, M.E., Activity of superior colliculus in behaving monkey. IlL Cells discharging before eye movements, J. NeurophysioL, 35 (1972) 575-586. 21 Wurtz, R.H. and Goldberg, M.E., Activity of superior colliculus in behaving monkey. IV. Effects of lesions on eye movements, J. Neurophysiol., 35 (1972) 587-596.
