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Projections from orbitofrontal cortex to mediodorsal thalamic nucleus in the dog
356
Brain Research, 131 (1977) 356-361 © Elsevier/North-Holland Biomedical Press
Projections from orbitofrontal cortex to mediodorsal thalamic nucleus in the dog
DUKE TANAKA, Jr. Department of Anatomy, Howard University, Collegeof Medicine, Washington, D.C. 20059 (U.S.A.)
(Accepted May 4th, 1977)
Many studies have investigated the behavioral effects of selective lesions of the orbitofrontal cortex in the dog1,2,3,5,10,11,17,18. Most of the data have shown that this region can be divided into lateral and medial sectors, with each mediating specific functions. Lesions of the dorsolateral convexity, made up of the proreal and dorsal part of the orbital gyri, have been shown to disrupt the execution of spatial delay tasks10,11. In contrast, lesions of the medial sector, involving the dorsomedial proreal gyrus, part of the precruciate gyrus, as well as most of the pregenual and subgenual gyri, do not affect spatial delay performance, but result in deficits in conditioned inhibition tasks 3 and changes in affective behaviorL Results of anatomical studies of thalamocortical projections to the canine orbitofrontal cortex have only partially supported the functional data. In the dog, the orbitofrontal region receives topographically organized projections ~z from the parvocellular (MDpc) and magnocellular (MDmc) divisions of the mediodorsal thalamic nucleus 5. However, in contrast to the situation in the monkey, in which functionally distinct dorsolateraP 3 and orbital 4 prefrontal sectors receive projections from MDpc and MDmc respectivelyz0, the functionally distinct dorsolateral and medial orbitofrontal sectors in the dog both receive projections from MDpc, while the ventrally located subproreal gyrus receives projections from MDmc ~2. This dorsal-ventral topographic arrangement of connections neither reflects nor supports the functional division of this region into lateral and medial sectors. Since this anatomical division is based entirely on results from studies of retrograde degeneration in MD 12,a6, this investigation was undertaken to determine whether the distribution of corticothalamic projections could provide additional anatomical support for the division of the canine orbitofrontal region into dorsal and ventral sectors. Eleven adult mongrel dogs (Canisfamiliaris) weighing 8.0-13.5 kg were used in this study. Following intraperitoneal administration of sodium pentobarbital (40 mg/kg), selective unilateral (10 animals) or bilateral (one animal) decortications of orbitofrontal sectors (dorsomedial proreal, dorsolateral proreal, orbital, pregenual, subgenual, subproreal, and medial precruciate) lesions were done by subpial aspiration. Lesions were placed within each of the major myeloarchitectonic divisions of
357
Fig. 1. Lateral and medial views of the dog cerebral hemispheres showing the principal areas of the frontal lobe as designated by KreinerL Abbreviations: ORB, orbital gyrus; PG, pregenual gyrus; PR, proreal gyrus; SG, subgenual gyrus; SPR, subproreal gyrus; XC, central precruciate area; XM, medial precruciate area; XP, posterior precruciate area. K r e i n e r 9 (Fig. 1). A f t e r survival p e r i o d s o f 5-11 days, the animals were deeply anesthetized a n d perfused i n t r a c a r d i a l l y with a 0.9~o saline solution followed by a 10~o f o r m a l i n - s a l i n e solution. The brains were e x p o s e d a n d left in situ in the fixative for at least 24 h, then b l o c k e d in the c o r o n a l plane, s o a k e d in 30 ~ s u c r o s e - f o r m a l i n solution, frozen, a n d sectioned at 30 ~ m . Every tenth section t h r o u g h the t h a l a m u s was processed with a modified F i n k - H e i m e r II silver i m p r e g n a t i o n m e t h o d 19. M a n y sections were subsequently c o u n t e r s t a i n e d with cresyl violet to a i d in the delineation o f t h a l a m i c boundaries. Sections were p r o j e c t e d using a m i c r o p r o j e c t o r a n d t h a l a m i c nuclei a n d m a j o r l a n d m a r k s traced. D e g e n e r a t i n g axons a n d p r e t e r m i n a l s were
431 Fig. 2. Surface reconstructions and cross-sections of the cortex and and mediodorsal thalamic nucleus (MD) in dogs with lesions of the dorsal sector of the orbitofrontal cortex. Preterminal degeneration is present in MDpc. The dark shading in the cortical drawings illustrates the depth and extent of the lesions. In the thalamus cross-sections, the wavy lines denote degenerating axons and the dots indicate preterminal degeneration. The numbers indicate the location of specific thalamic cross-sections in a consecutive series. The lower number in all cases indicates the more rostral section. A : lesion of the lateral proreal gyrus. B: lesion of the dorsomedial proreal gyrus. C: lesion of the medial precruciate area.
358 mapped and plotted onto the diagrams using the compound microscope. Additional sections through the orbitofrontal cortex were stained with cresyl violet and drawn at regular intervals to illustrate the location and extent of the lesion. Cortical designations are those of KreinerL Results obtained from selective cortical aspirations indicate that the orbitofrontal region is organized in a dorsal-ventral direction with respect to its projections to MDpc and MDmc. Lesions of both the lateral and medial surfaces of the dorsally located proreal gyrus resulted in preterminal degeneration in MDpc (Fig. 2A, B). After lesions of the dorsolateral part of this gyrus, degenerating preterminals were located centrally within the rostral part of MDpc. As more caudal levels of this nuclear division were reached, the degeneration appeared to shift slightly more medially. Following lesions of the dorsomedial part of the proreal gyrus and the pregenual area, degenerating fibers and preterminals were noted in the most lateral and dorsal parts of rostral MDpc, immediately adjacent to the paracentral and rostral part of the central lateral thalamic nuclei. Further caudally in MDpc, the degeneration shifted more centrally and gradually tapered off in density. Lesions of the dorsomedial part of the
x....
491
431
401
/,
461
Fig. 3. Surface reconstructions a n d cross-sections of the cortex a n d mediodorsal thalamic nucleus in dogs with lesions of the ventral sector of the orbitofrontal cortex. Preterminal degeneration is located in M D m c . A : lesion o f the lateral subproreal gyrus. B : lesion of the medial subproreal gyrus a n d the subgenual area.
359 precruciate gyrus (area XC) (Fig. 2C) also resulted in degeneration in MDpc. However, in contrast to the more rostrally located degeneration resulting from dorsomedial proreal lesions, the degeneration in this case appeared to be heavier and more extensive in the caudal part of MDpc, with very little degeneration seen in the rostral part of the nucleus. In addition, there were no degenerating preterminals noted in the ventral anterior or ventral lateral thalamic nuclei. Lesions of the subproreal and subgenual gyri resulted in preterminal degeneration in MDmc (Fig. 3). After lesions of the lateral surface of the subproreal gyrus, dense fiber and preterminal degeneration extended over most of the width and rostralcaudal extent of MDmc. In contrast, lesions of the medial surface of the subproreal gyrus and the ventral part of the subgenual gyrus resulted in a thin vertical band of degenerating preterminals located in MDmc immediately adjacent to the midline nuclei (Fig. 4). Degeneration was heaviest in the rostral part of MDmc with very little degeneration noted in the caudal part of the nucleus. Results obtained from lesions of the orbital gyrus indicated that this area may form a transition zone on the lateral surface between the MDpc-projecting cortical areas and the MDmc-projecting areas. That is, lesions of this gyrus resulted in axonal degeneration terminating in a diffuse pattern throughout both MDpc and MDmc. Degeneration was noted throughout the entire rostral-caudal extent of MD.
Fig. 4. Preterminal degeneration in MDmc 8 days after a medial subproreal and subgenual lesion. Note the sharp delineation between the midline nuclei to your left (practically free of degeneration) and MDmc (filledwith degenerating debris). Modified Fink-Heimer, × 600,
360 Overall, the projection field of the orbital gyrus appeared to occupy a greater lateralmedial extent in MD than did that of any other sector investigated. The results of this study show that, based on corticothalamic projections, the orbitofrontal region may be divided into dorsal and ventral sectors. Although this division contrasts with the separation of this region into lateral and medial sectors suggested by earlier behavioral data, it confirms previous anatomical findingslL The lateral to medial shift in preterminal degeneration within MD as the orbitofrontal lesion is moved from dorsal to ventral gyri is reminiscent of that seen after lesions of the primate prefrontal cortex s. However, although the general overall organization remains similar, uncertainties in the identification of the cytoarchitectonic divisions of MD in carnivores make more exact comparisons difficultlZ, 15. The finding of projections to MD from the medial part of the precruciate gyrus was not unexpected. Previous anatomical and functional data had strongly suggested that this sector is part of the orbitofrontal system. Gorska 6 found that the premotor or supplementary motor cortex does not extend onto the medial precruciate gyrus as it does in other carnivores such as the raccoon 7. Other studies have shown that lesions of the medial precruciate area result in retrograde degeneration in M DpO ~, and that severe impairments in inhibitory responses result from dorsomedial lesions involving portions of this area 17. In addition, Stepien and Stepien ~4 reported that hyper-orientation to a conditioned stimulus was regularly seen following large lesions of only the medial precruciate gyrus. This evidence suggests that deficits in inhibition usually associated with dorsomedial proreal lesions may in some cases be due to removal of all or part of the medial precruciate gyrus. On the other hand, deficits in inhibition can still occur following medial lesions that spare the medial precruciate area 2,5. However, in these cases the medial ablations are usually large, involving both the dorsal and ventral parts of the medial surface extensively. The present results obtained from the use of smaller and more discrete lesions show that a shift in thalamic connectivity occurs from MDpc to MDmc as the lesion is placed more ventrally on the medial surface. Since relatively isolated lesions of the Ml3mc-related subproreal gyrus yield only slight and transient behavioral deftcits ~s, it is suggested that in cases sparing the medial precruciate area, involvement of both dorsal and ventral parts 0fthe medial surface and their related MD divisions may be necessary to evoke major deficits in conditioned inhibition. Supported by NINCDS Grant NS12463 awarded to the author and by GRS 5S01RR05361 and Andrew W. Mellon Grants awarded to the Howard University College of Medicine. I thank Ms. Ophelia I. Weeks for her skilled technical assistance, Drs. W. L. R. Cruce, M. E. Goldberger, G. B. Stanton, and B. H. Turner for their critical comments on an earlier version of the manuscript, and Ms. Lonnie Jenkins for typing the manuscript.
361 1 Brutkowski, S., Prefrontal cortex and drive inhibition. In J. M. Warren and K. Akert (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, New York, 1964, pp. 242-270. 2 Brutkowski, S. and Dabrowska, J., Disinhibition after prefrontal lesions as a function of duration of intertrial intervals, Science, 139 (1963) 505-506. 3 Brutkowski, S. and Dabrowska, J., Prefrontal control of differential behavior in dogs, Acta biol. exp., 26 (1966) 425-439. 4 Butter, C. M., Synder, D. R. and McDonald, J. A., Effects of orbital frontal lesions on aversive and aggressive behavior in rhesus monkeys, J. comp. physiol. PsychoL, 72 (1970) 132-144. 5 Dabrowska, J., Prefrontal lesions and avoidance reflex differentiation in dogs, ,4cta neurobioL exp., 35 (1975) 1-15. 6 Gorska, T., Functional organization of cortical motor areas in adult dogs and puppies, Acta neurobiol, exp., 34 (1974) 171-203. 7 Jameson, H. D., Arumugasamy, N. and Hardin, Jr., W. B., The supplementary motor area of the raccoon, Brain Research, 11 (1968) 628-637. 8 Johnson, T. N., Rosvold, H. E. and Mishkin, M., Projections from behaviorally-defined sectors of the prefrontal cortex to the basal ganglia, septum and diencephalon in the monkey, Exp. Neurol., 21 (1968) 20-34. 9 Kreiner, J., The myeloarchitectonics of the frontal cortex of the dog, J. comp. Neurol., 116 (1961) 117-134. 10 Lawicka, W., A proposed mechanism for delayed response impairment in prefrontal animals, Acta biol. exp., 29 (1969) 401-414. 11 Lawicka, W., Mishkin, M., Kreiner, J. and Brutkowski, S., Delayed response deficit in dogs after selective ablation of the proreal gyrus, Acta biol. exp., 26 (1966) 309-322. 12 Narkiewicz, O. and Brutkowski, S., The organization of projections from the thalamic mediodorsal nucleus to the prefrontal cortex of the dog, J. comp. Neurol., 129 (1967) 361-374. 13 Stamm, J. S., Dorsolateral frontal ablations and response processes in monkeys, J. comp. physiol. Psychol., 70 (1970) 437-447. 14 Stepien, I. and Stepien, L., The effects of bilateral lesions in precruciate cortex on simple locomotor conditioned responses in dogs, Acta bioL exp., 25 (1965) 387-394. 15 Sychowa, B., The myeloarchitectonics of the dorsomedial thalamic nucleus of the dog, Acta neurobiol, exp., 30 (1970) 145-156. 16 Sychowa, B., Stepien, L. and Stepien, I., Degeneration in the thalamus following medial frontal lesions in the dog, Acta bioL exp., 28 (1968) 383-386. 17 Szwejkowska, G., Kreiner, J. and Sychowa, B., The effect of partial lesions of the prefrontal area on alimentary conditioned reflexes in dogs, Acta biol. exp., 23 (1963) 181-192. 18 Szwejkowska, G., Stepien, L. and Kreiner, J., The effect of subproreal lesions of the prefrontal area on alimentary conditioned reflexes in dogs, Acta biol. exp., 25 (1965) 373-377. 19 Tanaka, Jr., D., Thalamic projections of the dorsomedial prefrontal cortex in the rhesus monkey (Macaea mulatta), Brain Research, 110 (1976) 21-38. 20 Walker, A. E., The medial thalamic nucleus. A comparative anatomical, physiological and clinical study, J. comp. NeuroL, 73 (1940) 87-115.
Brain Research, 131 (1977) 356-361 © Elsevier/North-Holland Biomedical Press
Projections from orbitofrontal cortex to mediodorsal thalamic nucleus in the dog
DUKE TANAKA, Jr. Department of Anatomy, Howard University, Collegeof Medicine, Washington, D.C. 20059 (U.S.A.)
(Accepted May 4th, 1977)
Many studies have investigated the behavioral effects of selective lesions of the orbitofrontal cortex in the dog1,2,3,5,10,11,17,18. Most of the data have shown that this region can be divided into lateral and medial sectors, with each mediating specific functions. Lesions of the dorsolateral convexity, made up of the proreal and dorsal part of the orbital gyri, have been shown to disrupt the execution of spatial delay tasks10,11. In contrast, lesions of the medial sector, involving the dorsomedial proreal gyrus, part of the precruciate gyrus, as well as most of the pregenual and subgenual gyri, do not affect spatial delay performance, but result in deficits in conditioned inhibition tasks 3 and changes in affective behaviorL Results of anatomical studies of thalamocortical projections to the canine orbitofrontal cortex have only partially supported the functional data. In the dog, the orbitofrontal region receives topographically organized projections ~z from the parvocellular (MDpc) and magnocellular (MDmc) divisions of the mediodorsal thalamic nucleus 5. However, in contrast to the situation in the monkey, in which functionally distinct dorsolateraP 3 and orbital 4 prefrontal sectors receive projections from MDpc and MDmc respectivelyz0, the functionally distinct dorsolateral and medial orbitofrontal sectors in the dog both receive projections from MDpc, while the ventrally located subproreal gyrus receives projections from MDmc ~2. This dorsal-ventral topographic arrangement of connections neither reflects nor supports the functional division of this region into lateral and medial sectors. Since this anatomical division is based entirely on results from studies of retrograde degeneration in MD 12,a6, this investigation was undertaken to determine whether the distribution of corticothalamic projections could provide additional anatomical support for the division of the canine orbitofrontal region into dorsal and ventral sectors. Eleven adult mongrel dogs (Canisfamiliaris) weighing 8.0-13.5 kg were used in this study. Following intraperitoneal administration of sodium pentobarbital (40 mg/kg), selective unilateral (10 animals) or bilateral (one animal) decortications of orbitofrontal sectors (dorsomedial proreal, dorsolateral proreal, orbital, pregenual, subgenual, subproreal, and medial precruciate) lesions were done by subpial aspiration. Lesions were placed within each of the major myeloarchitectonic divisions of
357
Fig. 1. Lateral and medial views of the dog cerebral hemispheres showing the principal areas of the frontal lobe as designated by KreinerL Abbreviations: ORB, orbital gyrus; PG, pregenual gyrus; PR, proreal gyrus; SG, subgenual gyrus; SPR, subproreal gyrus; XC, central precruciate area; XM, medial precruciate area; XP, posterior precruciate area. K r e i n e r 9 (Fig. 1). A f t e r survival p e r i o d s o f 5-11 days, the animals were deeply anesthetized a n d perfused i n t r a c a r d i a l l y with a 0.9~o saline solution followed by a 10~o f o r m a l i n - s a l i n e solution. The brains were e x p o s e d a n d left in situ in the fixative for at least 24 h, then b l o c k e d in the c o r o n a l plane, s o a k e d in 30 ~ s u c r o s e - f o r m a l i n solution, frozen, a n d sectioned at 30 ~ m . Every tenth section t h r o u g h the t h a l a m u s was processed with a modified F i n k - H e i m e r II silver i m p r e g n a t i o n m e t h o d 19. M a n y sections were subsequently c o u n t e r s t a i n e d with cresyl violet to a i d in the delineation o f t h a l a m i c boundaries. Sections were p r o j e c t e d using a m i c r o p r o j e c t o r a n d t h a l a m i c nuclei a n d m a j o r l a n d m a r k s traced. D e g e n e r a t i n g axons a n d p r e t e r m i n a l s were
431 Fig. 2. Surface reconstructions and cross-sections of the cortex and and mediodorsal thalamic nucleus (MD) in dogs with lesions of the dorsal sector of the orbitofrontal cortex. Preterminal degeneration is present in MDpc. The dark shading in the cortical drawings illustrates the depth and extent of the lesions. In the thalamus cross-sections, the wavy lines denote degenerating axons and the dots indicate preterminal degeneration. The numbers indicate the location of specific thalamic cross-sections in a consecutive series. The lower number in all cases indicates the more rostral section. A : lesion of the lateral proreal gyrus. B: lesion of the dorsomedial proreal gyrus. C: lesion of the medial precruciate area.
358 mapped and plotted onto the diagrams using the compound microscope. Additional sections through the orbitofrontal cortex were stained with cresyl violet and drawn at regular intervals to illustrate the location and extent of the lesion. Cortical designations are those of KreinerL Results obtained from selective cortical aspirations indicate that the orbitofrontal region is organized in a dorsal-ventral direction with respect to its projections to MDpc and MDmc. Lesions of both the lateral and medial surfaces of the dorsally located proreal gyrus resulted in preterminal degeneration in MDpc (Fig. 2A, B). After lesions of the dorsolateral part of this gyrus, degenerating preterminals were located centrally within the rostral part of MDpc. As more caudal levels of this nuclear division were reached, the degeneration appeared to shift slightly more medially. Following lesions of the dorsomedial part of the proreal gyrus and the pregenual area, degenerating fibers and preterminals were noted in the most lateral and dorsal parts of rostral MDpc, immediately adjacent to the paracentral and rostral part of the central lateral thalamic nuclei. Further caudally in MDpc, the degeneration shifted more centrally and gradually tapered off in density. Lesions of the dorsomedial part of the
x....
491
431
401
/,
461
Fig. 3. Surface reconstructions a n d cross-sections of the cortex a n d mediodorsal thalamic nucleus in dogs with lesions of the ventral sector of the orbitofrontal cortex. Preterminal degeneration is located in M D m c . A : lesion o f the lateral subproreal gyrus. B : lesion of the medial subproreal gyrus a n d the subgenual area.
359 precruciate gyrus (area XC) (Fig. 2C) also resulted in degeneration in MDpc. However, in contrast to the more rostrally located degeneration resulting from dorsomedial proreal lesions, the degeneration in this case appeared to be heavier and more extensive in the caudal part of MDpc, with very little degeneration seen in the rostral part of the nucleus. In addition, there were no degenerating preterminals noted in the ventral anterior or ventral lateral thalamic nuclei. Lesions of the subproreal and subgenual gyri resulted in preterminal degeneration in MDmc (Fig. 3). After lesions of the lateral surface of the subproreal gyrus, dense fiber and preterminal degeneration extended over most of the width and rostralcaudal extent of MDmc. In contrast, lesions of the medial surface of the subproreal gyrus and the ventral part of the subgenual gyrus resulted in a thin vertical band of degenerating preterminals located in MDmc immediately adjacent to the midline nuclei (Fig. 4). Degeneration was heaviest in the rostral part of MDmc with very little degeneration noted in the caudal part of the nucleus. Results obtained from lesions of the orbital gyrus indicated that this area may form a transition zone on the lateral surface between the MDpc-projecting cortical areas and the MDmc-projecting areas. That is, lesions of this gyrus resulted in axonal degeneration terminating in a diffuse pattern throughout both MDpc and MDmc. Degeneration was noted throughout the entire rostral-caudal extent of MD.
Fig. 4. Preterminal degeneration in MDmc 8 days after a medial subproreal and subgenual lesion. Note the sharp delineation between the midline nuclei to your left (practically free of degeneration) and MDmc (filledwith degenerating debris). Modified Fink-Heimer, × 600,
360 Overall, the projection field of the orbital gyrus appeared to occupy a greater lateralmedial extent in MD than did that of any other sector investigated. The results of this study show that, based on corticothalamic projections, the orbitofrontal region may be divided into dorsal and ventral sectors. Although this division contrasts with the separation of this region into lateral and medial sectors suggested by earlier behavioral data, it confirms previous anatomical findingslL The lateral to medial shift in preterminal degeneration within MD as the orbitofrontal lesion is moved from dorsal to ventral gyri is reminiscent of that seen after lesions of the primate prefrontal cortex s. However, although the general overall organization remains similar, uncertainties in the identification of the cytoarchitectonic divisions of MD in carnivores make more exact comparisons difficultlZ, 15. The finding of projections to MD from the medial part of the precruciate gyrus was not unexpected. Previous anatomical and functional data had strongly suggested that this sector is part of the orbitofrontal system. Gorska 6 found that the premotor or supplementary motor cortex does not extend onto the medial precruciate gyrus as it does in other carnivores such as the raccoon 7. Other studies have shown that lesions of the medial precruciate area result in retrograde degeneration in M DpO ~, and that severe impairments in inhibitory responses result from dorsomedial lesions involving portions of this area 17. In addition, Stepien and Stepien ~4 reported that hyper-orientation to a conditioned stimulus was regularly seen following large lesions of only the medial precruciate gyrus. This evidence suggests that deficits in inhibition usually associated with dorsomedial proreal lesions may in some cases be due to removal of all or part of the medial precruciate gyrus. On the other hand, deficits in inhibition can still occur following medial lesions that spare the medial precruciate area 2,5. However, in these cases the medial ablations are usually large, involving both the dorsal and ventral parts of the medial surface extensively. The present results obtained from the use of smaller and more discrete lesions show that a shift in thalamic connectivity occurs from MDpc to MDmc as the lesion is placed more ventrally on the medial surface. Since relatively isolated lesions of the Ml3mc-related subproreal gyrus yield only slight and transient behavioral deftcits ~s, it is suggested that in cases sparing the medial precruciate area, involvement of both dorsal and ventral parts 0fthe medial surface and their related MD divisions may be necessary to evoke major deficits in conditioned inhibition. Supported by NINCDS Grant NS12463 awarded to the author and by GRS 5S01RR05361 and Andrew W. Mellon Grants awarded to the Howard University College of Medicine. I thank Ms. Ophelia I. Weeks for her skilled technical assistance, Drs. W. L. R. Cruce, M. E. Goldberger, G. B. Stanton, and B. H. Turner for their critical comments on an earlier version of the manuscript, and Ms. Lonnie Jenkins for typing the manuscript.
361 1 Brutkowski, S., Prefrontal cortex and drive inhibition. In J. M. Warren and K. Akert (Eds.), The Frontal Granular Cortex and Behavior, McGraw-Hill, New York, 1964, pp. 242-270. 2 Brutkowski, S. and Dabrowska, J., Disinhibition after prefrontal lesions as a function of duration of intertrial intervals, Science, 139 (1963) 505-506. 3 Brutkowski, S. and Dabrowska, J., Prefrontal control of differential behavior in dogs, Acta biol. exp., 26 (1966) 425-439. 4 Butter, C. M., Synder, D. R. and McDonald, J. A., Effects of orbital frontal lesions on aversive and aggressive behavior in rhesus monkeys, J. comp. physiol. PsychoL, 72 (1970) 132-144. 5 Dabrowska, J., Prefrontal lesions and avoidance reflex differentiation in dogs, ,4cta neurobioL exp., 35 (1975) 1-15. 6 Gorska, T., Functional organization of cortical motor areas in adult dogs and puppies, Acta neurobiol, exp., 34 (1974) 171-203. 7 Jameson, H. D., Arumugasamy, N. and Hardin, Jr., W. B., The supplementary motor area of the raccoon, Brain Research, 11 (1968) 628-637. 8 Johnson, T. N., Rosvold, H. E. and Mishkin, M., Projections from behaviorally-defined sectors of the prefrontal cortex to the basal ganglia, septum and diencephalon in the monkey, Exp. Neurol., 21 (1968) 20-34. 9 Kreiner, J., The myeloarchitectonics of the frontal cortex of the dog, J. comp. Neurol., 116 (1961) 117-134. 10 Lawicka, W., A proposed mechanism for delayed response impairment in prefrontal animals, Acta biol. exp., 29 (1969) 401-414. 11 Lawicka, W., Mishkin, M., Kreiner, J. and Brutkowski, S., Delayed response deficit in dogs after selective ablation of the proreal gyrus, Acta biol. exp., 26 (1966) 309-322. 12 Narkiewicz, O. and Brutkowski, S., The organization of projections from the thalamic mediodorsal nucleus to the prefrontal cortex of the dog, J. comp. Neurol., 129 (1967) 361-374. 13 Stamm, J. S., Dorsolateral frontal ablations and response processes in monkeys, J. comp. physiol. Psychol., 70 (1970) 437-447. 14 Stepien, I. and Stepien, L., The effects of bilateral lesions in precruciate cortex on simple locomotor conditioned responses in dogs, Acta bioL exp., 25 (1965) 387-394. 15 Sychowa, B., The myeloarchitectonics of the dorsomedial thalamic nucleus of the dog, Acta neurobiol, exp., 30 (1970) 145-156. 16 Sychowa, B., Stepien, L. and Stepien, I., Degeneration in the thalamus following medial frontal lesions in the dog, Acta bioL exp., 28 (1968) 383-386. 17 Szwejkowska, G., Kreiner, J. and Sychowa, B., The effect of partial lesions of the prefrontal area on alimentary conditioned reflexes in dogs, Acta biol. exp., 23 (1963) 181-192. 18 Szwejkowska, G., Stepien, L. and Kreiner, J., The effect of subproreal lesions of the prefrontal area on alimentary conditioned reflexes in dogs, Acta biol. exp., 25 (1965) 373-377. 19 Tanaka, Jr., D., Thalamic projections of the dorsomedial prefrontal cortex in the rhesus monkey (Macaea mulatta), Brain Research, 110 (1976) 21-38. 20 Walker, A. E., The medial thalamic nucleus. A comparative anatomical, physiological and clinical study, J. comp. NeuroL, 73 (1940) 87-115.