Abhisek C. Khandai

EXTERNAL CONNECTIONS OF THE DORSOLATERAL PREFRONTAL CORTEX. Abhisek C. Khandai¹, Joseph L. Price², K.S. Saleem². Biology Department, Washington University, St. Louis, MO¹; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO².

Executive functions- skills like decision-making, attention, planning, goal-directed behavior - have been found to take place in the prefrontal cortex (the cortex anterior to the motor cortex). The prefrontal cortex of monkeys and humans consists of at least two different regions, the orbitomedial (OMPFC) and dorsolateral prefrontal cortex (DLPFC). These areas can be further divided into areas based on cellular (architectonic) differences. These areas can be categorized into regions based on intrinsic connections, as well as differing external axonal connections to other parts of the brain, providing insight into the region’s function. Previous studies of the Price lab have analyzed in depth the connections of the orbitomedial region. These studies have shown that there are two distinct and complementary “networks” within the orbital (ventral) and medial regions of the OMPFC, the former being linked to food sensation and reward, the latter involved in visceral awareness. However, the analysis of the DLPFC has been incomplete, although previous studies have identified a number of architectonic areas, while other studies have examined external axonal connections. These earlier findings suggest the presence of several distinct regions within the DLPFC, each having different connections and functions. Three regions have been hypothesized in the ventral, caudal, and dorsal areas of the DLPFC.

To study these cortico-cortical connections, retrograde and anterograde axonal tracers were injected into the various hypothesized regions of the DLPFC in macaque monkeys (macaca mulatta), valuable animal models in their high structural homology to the human brain. After sacrifice, the brains were prepared for histological staining and demonstration of the tracers. The brains were then serially sectioned via microtome to create coronal brain slices, to easily visualize labeling of cells and axons by tracers in various parts of the brain. These slices were mapped, rostrally to caudally from the premotor cortex to the posterior temporal cortex, using the Accustage MDPlot 5.2.0 computer and microscope system. The maps of successive sections were elaborated with grey-white matter boundaries, and collated to produce composite images of areas of the cortex, allowing patterns of connections to be readily visualized across the brain.

The resulting patterns of cortico-cortical connections exhibited clearly distinct systems of labeling from each injected region, leading to differing functional areas. This supports the hypothesis of relatively close areas geographically in the DLPFC belonging to different functional systems. However, more injections must be made into other parts of the DLPFC, and continuing analysis of labeling needs to be done, before the hypothetical ventral, caudal, and dorsal areas can be sufficiently delineated or disproven. Further study will lead to both better discrimination of separate functional areas within the DLPFC, as well as understanding its own overall functional role in the brain. The importance of such “neuro-cartography” cannot be understated. Apart from an elucidation of the executive functions of the brain, the DLPFC has also been implicated in various psychiatric diseases, from depression to schizophrenia. Understanding of connections and subdivisions within this region can hopefully lead to both better diagnoses of such brain disorders, and perhaps better treatment via the increased knowledge of the neuroanatomy.