The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion, Decision Making, Social Cognition, and Psychopathology

Abstract

The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders.

Keywords: Decision making; Emotion; Neuroanatomy; Prefrontal cortex; Psychopathology; Social cognition.

Figure 1. Functionally specialized subregions of vmPFC

Meta-analyses from Neurosynth yielded reverse inference statistical maps for each of the three domains (value and decision-making, emotion, and social). For each domain, we selected three keywords that we used as search terms to identify loci of domain-related activity (coded in different shades of green within each row). For the value and decision-making domain, we used search terms “value”, “reward”, and “decision-making”; for the emotion domain we used search terms “threat”, “emotional”, and “conditioning”; and for the social domain we used search terms “social”, “moral”, and “theory of mind”. The area of overlap within each domain (coded in red in the top three rows) was similar regardless of which specific domain-relevant search terms we used (i.e., using “fear” instead of “threat”, “empathy” instead of “moral”, or “reward anticipation” instead of “reward” yields nearly identical results). The bottom row shows the areas of overlap for each domain in different colors. This analysis demonstrates distinct subregions within vmPFC as well as distinct patterns of co-activation outside of vmPFC for each domain.

Figure 2. Association between vmPFC subregions and psychiatric disorders

To define activation loci associated with each disorder, we used the results of previously published meta-analyses of fMRI findings related to each disorder to construct spheres representing the approximate volume of reported clusters at their respective peak coordinates (for details see Supplementary Methods, Supplementary Table 1, and Supplementary Figure 1). Meta-analyses were obtained by searching the PubMed database. The search terms included the combination of terms for each disorder (e.g., “depression”, “PTSD”, “addiction”, “social anxiety disorder”, etc.), “fMRI”, and “meta-analysis”. The search was restricted to meta-analyses of event-related fMRI studies of adults that were listed in the database on or after January 1st, 2006. Overlap between the disorder-related loci and functionally specialized vmPFC subregions (as defined in Figure 1) is shown in yellow (for value and decision-making), purple (for emotion), and aqua (for social), corresponding to the color scheme in the bottom row of Figure 1. Two sagittal slices were selected for each disorder to illustrate all regions of overlap.