Subdivisions and Connectional Networks of the Lateral Prefrontal Cortex in the Macaque Monkey Kadharbatcha S. Saleem, 1,2 * Brad Miller, 1 and Joseph L. Price 1 1 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 2 Laboratory of Neuropsychology, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland 20892 ABSTRACT Neuroanatomical studies have long indicated that corti- cocortical connections are organized in networks that relate distinct sets of areas. Such networks have been emphasized by development of functional imaging methods for correlating activity across the cortex. Previ- ously, two networks were recognized in the orbitome- dial prefrontal cortex, the “orbital” and “medial” networks (OPFC and MPFC, respectively). In this study, three additional networks are proposed for the lateral prefrontal cortex: 1) a ventrolateral network (VLPFC) in and ventral to the principal sulcus; 2) a dorsal network (DPFC) in and dorsal to the principal sulcus and in the frontal pole; 3) a caudolateral network (CLPFC) in and rostral to the arcuate sulcus and the caudal principal sulcus. The connections of the first two networks are described here. Areas in each network are connected primarily with other areas in the same network, with overlaps around the principal sulcus. The VLPFC and DPFC are also connected with the OPFC and MPFC, respectively. Outside the prefrontal cortex, the VLPFC connects with specific areas related to somatic/visceral sensation and vision, in the frontoparietal operculum, insula, ventral bank/fundus of the superior temporal sulcus, inferior temporal gyrus, and inferior parietal cor- tex. In contrast, the DPFC connects with the rostral superior temporal gyrus, dorsal bank of the superior temporal sulcus, parahippocampal cortex, and posterior cingulate and retrosplenial cortex. Area 45a, in caudal VLPFC, is unique, having connections with all the net- works. Its extrinsic connections resemble those of the DPFC. In addition, it has connections with both auditory belt/parabelt areas, and visual related areas. J. Comp. Neurol. 522:1641–1690, 2014. V C 2013 Wiley Periodicals, Inc. INDEXING TERMS: LPFC; VLPFC; DPFC; CLPFC; OMPFC; OPFC; MPFC; superior temporal gyrus; parietal cortex; infe- rior temporal cortex; superior temporal sulcus; insula; connections Although the prefrontal cortex (PFC) in primates, defined as the region rostral to the “frontal” motor areas, does not have obvious sensory or motor roles, it has been associated with many functions. Perhaps the most common is “executive function,” but this vague and ultimately unsatisfactory designation subsumes a number of subordinate functions. Attention, spatial and nonspatial working memory, assessment of food stimuli, reward-guided behavior, anticipation of reward or aver- sion, emotional behavior, and mood have all been attributed to the PFC (Mishkin and Manning, 1978; Levy and Goldman-Rakic, 2000; Miller, 2000; € Ong€ ur and Price, 2000; Rolls, 2000; Rushworth et al., 2005; Petrides, 2005; Meyer et al., 2011; Noonan et al., 2011; Rudebeck and Murray, 2011b; Price and Drevets, 2012; Passingham and Wise, 2012). Because the PFC as a whole is large and heterogeneous, it is likely that these and other functions are not represented evenly across the many architectonic areas that make it up. Instead, it may be presumed that the PFC is divided into several networks that have distinct roles. The development of methods that are purported to demonstrate “functional connections” with MRI (fcMRI) has led to the description of several corticocortical net- works. These link widespread cortical areas in several parts of the cortex and are presumed to underlie Grant sponsor: National Institutes of Health; Grant number: MH70941; Grant sponsor: McDonnell Center for Higher Brain Function; Grant sponsor: National Institute of Mental Health Intramural Research Program. *CORRESPONDENCE TO: Kadharbatcha Saleem, PhD, Laboratory of Neuropsychology, National Institute of Mental Health, 49 Convent Drive, Bldg. 49, 1B80 MSc. 4415, Bethesda, MD 20892. E-mail: saleemks@mail.nih.gov Received June 12, 2013; Revised October 31, 2013; Accepted October 31, 2013. DOI 10.1002/cne.23498 Published online November 9, 2013 in Wiley Online Library (wileyonlinelibrary.com) V C 2013 Wiley Periodicals, Inc. The Journal of Comparative Neurology | Research in Systems Neuroscience 522:1641–1690 (2014) 1641 RESEARCH ARTICLE