The Statistical Neuroanatomy of Frontal Networks in the Macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework.Author Summary: The anatomical input to a cortical area defines, to a large extent, the functions that the area can perform. For example, if an area has no visual inputs, it cannot carry out computations on visual information. Therefore, understanding the inputs to a patch of cortex can provide fundamental insight into the function of the area. Anatomical tract tracing studies in macaque monkeys have defined much of the connectivity between areas of the macaque brain. We compiled the information on the anatomical inputs to 25 cytoarchitectonically defined frontal cortical areas. In its raw form, this connectivity is immensely complex, and the dominant inputs to each area cannot be clearly seen. To reduce the complexity, we carried out hierarchical cluster analysis on the areas based upon their inputs. We found a statistically robust organization of the areas. Identified clusters corresponded to anatomically contiguous groups, including orbital, ventral-medial, dorsal-medial, ventral-lateral, and dorsal-lateral areas. Using these groups, we were able to clearly define the dominant inputs to each cluster. We found that ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups were defined by exterosensory, limbic, motor, exterosensory, and chemosensory inputs, respectively. These inputs likely drive the physiological responses found in each area.