Why we need nonhuman primates to study the role of ventromedial prefrontal cortex in the regulation of threat- and reward-elicited responses

Abstract

The ventromedial prefrontal cortex (vmPFC) is consistently implicated in the cognitive and emotional symptoms of many psychiatric disorders, but the causal mechanisms of its involvement remain unknown. In part, this is because of the poor characterization of the disorders and their symptoms, and the focus of experimental studies in animals on subcortical (rather than cortical) dysregulation. Moreover, even in those experimental studies that have focused on the vmPFC, the preferred animal model for such research has been the rodent, in which there are marked differences in the organization of this region to that seen in humans, and thus the extent of functional homology is unclear. There is also a paucity of well-defined behavioral paradigms suitable for translating disorder-relevant findings across species. With these considerations in mind, we discuss the value of nonhuman primates (NHPs) in bridging the translational gap between human and rodent studies. We focus on recent investigations into the involvement in reward and threat processing of 2 major regions of the vmPFC, areas 25 and 32 in NHPs and their anatomical homologs, the infralimbic and prelimbic cortex, in rodents. We highlight potential similarities, but also differences between species, and consider them in light of the extent to which anatomical homology reflects functional homology, the expansion of the PFC in human and NHPs, and most importantly how they can guide future studies to improve the translatability of findings from preclinical animal studies into the clinic.