The Journal of Neuroscience, November 1988, 8(11): 4049-4088 Common Cortical and Subcortical Targets of the Dorsolateral Prefrontal and Posterior Parietal Cortices in the Rhesus Monkey: Evidence for a Distributed Neural Network Subserving Spatially Guided Behavior L. D. Selemon and P. S. Goldman-Rakic Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510 Common efferent projections of the dorsolateral prefrontal project to the intermediate layers of the superior colliculus cortex and posterior parietal cortex were examined in 3 rhe- and to the midline reticular formation of the pons. sus monkeys by placing injections of tritiated amino acids The present study has uncovered a remarkably large num- and HRP in frontal and parietal cortices, respectively, of the ber of cortical and subcortical areas that receive input from same hemisphere. Terminal labeling originating from both both the dorsolateral prefrontal and posterior parietal as- frontal and parietal injection sites was found to be in ap- sociation cottices, indicating that these common efferent position in 15 ipsilateral cortical areas: the supplementary pathways constitute part of an elaborate anatomical circuit motor cortex, the dorsal premotor cortex, the ventral pre- which could mediate many aspects of spatial function, in- motor cortex, the anterior arcuate cortex (including the fron- cluding spatial perception, attention, memory, and spatially tal eye fields), the orbitofrontal cortex, the anterior and pos- guided movement. terior cingulate cortices, the frontoparietal operculum, the insular cortex, the medial parietal cortex, the superior tem- The dorsolateral prefrontal cortex and the posterior parietal poral cortex, the parahippocampal gyrus, the presubiculum, cortex are perhapsthe most densely, reciprocally interconnected the caudomedial lobule, and the medial prestriate cortex. areasof associationcortex in the primate brain (Leichnetz, 1980; Convergent terminal labeling was observed in the contra- Goldman-Rakic and Schwartz, 1982; Schwartz and Goldman- lateral hemisphere as well, most prominently in the principal Rakic, 1982, 1984). Moreover, a recent detailed analysisof the sulcal cortex, the superior arcuate cortex, and the superior intracortical connections of these areashas revealed that each temporal cortex. In certain common target areas, as for ex- of the subdivisionsof the posterior parietal cortex (areas7a, 7b, ample the cingulate cortices, frontal and parietal efferents 7ip, and 7m) is specifically connected with a distinct subregion terminate in an array of interdigitating columns, an arrange- of the principal sulcalcortex (Cavadaand Goldman-Rakic, 1985). ment much like that observed for callosal and associational Thus, multiple reciprocal corticocortical projections intercon- projections to the principal sulcus (Goldman-Rakic and nect the prefrontal and parietal cortices and provide an ana- Schwartz, 1982). In other areas, frontal and parietal terminals tomical substrate for transfer of information between these 2 exhibit a laminar complementarity: in the depths of the su- areasof higher associationcortex. perior temporal sulcus, prefrontal terminals are densely dis- The dorsolateral prefrontal cortex and the posterior parietal tributed within laminae I, Ill, and V, whereas parietal termi- cortex may be related functionally as well. Physiologicalstudies nals occupy mainly laminae IV and VI directly below the have shown that the posterior parietal cortex mediatesspatial prefrontal bands. Subcortical structures also receive ap- perception by transforming the retinotopic image into a map of posing or overlapping projections from both prefrontal and visual space(Andersen et al., 1985) and is involved in relating parietal cortices. The dorsolateral prefrontal and posterior body position to this map of visual space(Hyvarinen and Por- parietal cortices project to adjacent, longitudinal domains of anen, 1974; Mountcastle et al., 1975), while the dorsolateral the neostriatum, as has been described previously (Selemon prefrontal cortex plays a central role in tasksthat require spatial and Goldman-Rakic, 1985); these projections are also found memory, such as the delayed responseand delayed alternation in close apposition in the claustrum, the amygdala, the cau- tasks (Goldman and Rosvold, 1970; Goldman et al., 1971; Fu- domedial lobule, and throughout the anterior medial, medial nahashi et al., 1986). Furthermore, lesionsin presumably ho- dorsal, lateral dorsal, and medial pulvinar nuclei of the thal- mologousregions of the prefrontal or parietal cortex in humans amus. In the brain stem, both areas of association cortex result in altered spatial perception and often in sensoryneglect of spacecontralateral to the lesion (Holmes, 1918; Denny-Brown and Banker, 1952; Critchley, 1953;Htcaen et al., 1956;Heilman Received Aug. 14, 1987; revised Mar. 7, 1988; accepted Mar. 8, 1988. and Valenstein, 1972). This work was supported by USPHS Grants MH38546 and MH00298 (P.S.G.-R.) In the present study we have examined the common outflow and an NIA fellowship award AGO53 10 (L.D.S.). We wish to thank J. Cobum, M. Pappy, L. Ladewig, and J. Musco for excellent technical assistance and Dr. R. pathways of the dorsolateral prefrontal and posterior parietal Williiims for advice on Figure 3. corticesusing a double anterogradelabeling method that allowed Correspondence should be addressed to Dr. P. S. Goldman-Rakic, Section of Neuroanatomy, Yale University School of Medicine, 333 Cedar Street, Rm. C303 usto visualize the prefrontal and parietal projections in adjacent SHM, New Haven, CT 065 10. sections.While numerous studieshave traced the efferent con- Copyright 0 1988 Society for Neuroscience 0270-6474/88/l 14049-20%02.00/O nections of each of thesecortical areas(see Table l), the present 4050 Selemon and Goldman-Rakic l Prefrontal and Parietal Projections Table 1. Anatomical evidence for prefrontal and parietal target areas based on single labeling of projections Target areas Prefrontal Parietal Supplementary motor area Pandya and Kuypers, 1969. Pandya and Kuypers, 1969” (area 6) Pandya et al., 19710 Petrides and Pandya, 1984* Jlirgens, 1984* Jiirgens, 1984* Dorsal premotor cortex Pandya and Kuypers, 1969 Pandya and Kuypers, 1969 (area 6cu) Pandya et al., 197 1 Chavis and Pandya, 1976 Barbas and Pandya, 1987b Petrides and Pandya, 1984 Ventral premotor cortex Pandya and Kuypers, 1969 Pandya and Kuypers, 1969 (area 60) Pandya et al., 197 1 Chavis and Pandya, 1976 Matelli et al., 1986b Petrides and Pandya, 1984 Barbas and Pandya, 1987b Godschalk et al., 1984b Matelli et al., 1986b Anterior arcuate cortex Pandya and Kuypers, 1969 Pandya and Kuypers, 1969 (area 8) Pandya et al., 197 1 Jones and Powell, 1970 Goldman and Nauta, 1977a Chavis and Pandya, 1976 Barbas and Mesulam, 198 1 b Barbas and Mesulam, 198 1 b Huerta et al., 1987b Petrides and Pandya, 1984 Huerta et al.. 1987b Orbitofrontal cortex Pandya et al., 1971 Cavada and Goldman-Rakic, 1986 (area 11) Goldman and Nauta, 1977a Anterior cingulate cortex Pandya and Kuypers, 1969 Pandya and Kuypers, 1969 (area 24) Pandya et al., 197 1 Jones and Powell, 1970 Goldman and Nauta, 1977a Baleydier and Mauguiere, 1980b Baleydier and Mauguiere, 1980b Petrides and Pandya, 1984 Posterior cingulate cortex Pandya and Kuypers, 1969 Pandya and Kuypers, 1969 (area 23) Pandya et al., 197 1 Jones and Powell, 1970 Goldman and Nauta, 1977a Baleydier and Mauguiere, 1980b Baleydier and Mauguiere, 1980b Petrides and Pandya, 1984 Frontoparietal operculum Pandya et al., 197 1 Pandya and Kuypers, 1969 (areas 1 ,Z,SII) Preuss and Goldman-Rakic, Pandya and Seltzer, 1982 1985 Petrides and Pandya, 1984 Insular cortex (area IG) Pandya et al., 197 1 Mufson and Mesulam, 1982b Goldman and Nauta, 1977a Mufson and Mesulam, 1982b Medial parietal cortex Goldman and Nauta, 1977ac Pandya and Kuypers, 1969* (area 7m) Pandva and Seltzer. 1982 Superior temporal cortex Pandya and Kuypers, 1969 Pandya and Kuypers, 1969 (area IPa) Pandya et al., 1971 Jones and Powell, 1970 Goldman and Nauta, 1977a Seltzer and Pandya, 1978 Seltzer and Pandva. 1984 Presubiculum Goldman-Rakic et al., 1984 Seltzer and Van Hoesen, 1979 Seltzer and Pandya, 1984 Parahippocampal gyrus Pandya and Kuypers, 1969 Jones and Powell, 1970 (area TF) Pandya et al., 197 1 Seltzer and Pandya, 1984 Goldman-Rakic et al., 1984 Caudomedial lobule Goldman-Rakic et al., 1984 Cavada and Goldman-Rakic, 1986 Medial prestriate cortex NPD Cavada and Goldman-Rakic, 1986 (area 19) Neostriatum Goldman and Nauta, 1977b Yeterian and Van Hoesen, 1978 Selemon and Goldman-Rakic, 1985 Amygdala AggIeton et al., 1980b Aggleton et al., 1980b Claustrum Pearson et al., 1982 Pearson et al., 1982 The Journal of Neuroscience, November 1988, 8(11) 4051 Table 1. Continued Target areas Prefrontal Parietal Thalamus Jacobsen et al., 1978 Asanuma et al., 1985 Ktinzle, 1978 Yeterian and Pandya, 1985 Preuss and Goldman-Rakic, 1987 Superior colliculus Kuypers and Lawrence, 1967 Kuypers and Lawrence, 1967 Goldman and Nauta, 1976 Asanuma et al., 1985 Leichnetz et al., 198 1 b Lynch et al., 1985 Pontine reticular formation Brodal, 1980 Kuypers and Lawrence, 1967 Leichnetz et al., 1984b NPD, not previously described. y Projections that were shown in published diagrams but not included in the descriptive passage of the text. b Evidence for projections based on placement of retrograde tracer in the target area. c Target area referred to as retrosplenial cortex. study has focused more specifically on the efferent