Cortical Granularity Shapes the Organization of Afferent Paths to the Amygdala and Its Striatal Targets in Nonhuman Primate

Abstract

The prefrontal cortex (PFC) and insula, amygdala, and striatum form interconnected networks that drive motivated behaviors. We previously found a connectional trend in which granularity of the ventromedial and orbital PFC/insula predicted connections to the amygdala, and also the breadth of amygdalo-striatal efferents, including projections beyond the “classic” ventral striatum. To further interrogate connectional relationships among the cortex, amygdala, and striatum, and to further define the “limbic” (amygdala-recipient) striatum, we conducted tract tracing studies in two cohorts of macaques (male n = 14, female n = 1). We focused on the cortico-amygdalo-striatal (indirect) and cortico-“limbic” striatal (direct) paths originating in the entire PFC and insula. Larger datasets and a quantitative approach revealed “cortical rules” in which cortical granularity predicts the complexity and location of projections to both the basal nucleus of the amygdala and striatum. Remarkably, projections from “cortical-like” basal nucleus to the striatum followed similar patterns. In both “direct” and “indirect” paths to the “limbic” striatum, agranular cortices formed a “foundational,” broad projection, and were joined by inputs from progressively more differentiated cortices. In amygdalo-striatal paths, the ventral basal nucleus was the “foundational” input, with progressively more dorsal basal nucleus regions gradually adding inputs as the “limbic” striatum extended caudally. Together, the “indirect” and “direct” paths followed consistent principles in which cortical granularity dictated the strength and complexity of projections at their targets. Cluster analyses independently confirmed these connectional trends, and also highlighted connectional features that predicted termination in specific subregions of the basal nucleus and “limbic” striatum.