Comparing the limbic-frontal connectome across the primate order: conservation of connections and implications for translational neuroscience

Abstract

The interaction of the limbic system and frontal cortex of the primate brain is important in many affective behaviors. For this reason, it is heavily implicated in a number of psychiatric conditions. This system is often studied in the macaque monkey, the most largely-used non-human primate model species. However, how evolutionary conserved this system is and how well results obtained in any model species translate to the human brain can only be understood by studying its organization across the primate order. Here, we present an investigation of the topology of limbic-frontal connections across seven species, representing all major branches of the primate family tree: humans (13 females, 11 males), chimpanzee (1 female), gorilla (1 male), gibbon (1 male), macaque (1 female, 2 males), squirrel monkey (1 female, 2 males), lemur (3 males). We show that dichotomous organization of amygdalofugal and uncinate connections with frontal cortex is conserved across all species. Subgenual connectivity of the cingulum bundle, however, seems less prominent in prosimian and New World monkey brains. These results inform both translational neuroscience and primate brain evolution.<b>Significance statement</b> The interaction between the limbic system and the frontal cortex is critical for affective behaviors and is implicated in psychiatric conditions. While often studied in macaques, understanding how conserved these circuits are across primates is essential for translational relevance. Here, we investigate limbic-frontal connections across seven primate species, spanning all major evolutionary branches. We demonstrate that the dichotomous organization of amygdalofugal and uncinate pathways is conserved, while subcallosal cingulate connectivity of the cingulum bundle is less prominent in prosimian and New World monkeys. These findings provide key insights into the evolution of primate brains and enhance our understanding of the translational potential of non-human primate models for studying human brain function and disorders.