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

doi:10.1016/j.biopsych.2017.10.030

Biological Psychiatry

Volume 83, Issue 8, 15 April 2018, Pages 638-647

https://doi.org/10.1016/j.biopsych.2017.10.030 Get rights and content

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.

Section snippets

Anatomy of the vmPFC

In the primate brain, “vmPFC” generally refers to an interconnected network of regions in the lower medial and orbital prefrontal cortices 1, 2, 3, 4. In rodents, the infralimbic cortex is typically considered to be related to human and monkey Brodmann area 25, a component of the vmPFC 2, 4. It is important to note that the term “vmPFC” does not refer to a discrete brain structure with clearly defined and uniformly applied anatomical borders, such as a specific nucleus or gyrus. The use of the

Value and Decision Making

One of the seminal clinical observations of human neurological patients with focal vmPFC damage is a severe defect in value-based decision making, despite intact performance on conventional measures of intelligence 5, 6. This behavioral defect was first captured in the laboratory with a gambling task that requires subjects to learn about rewards and punishments under conditions of risk, ambiguity, and reversing contingencies (7). Subsequent studies of vmPFC lesion patients have documented

Emotion Regulation

A second domain of function in which vmPFC is theorized to play a major role is the regulation of negative emotion. An elegant series of rodent studies using a fear conditioning and extinction paradigm provided the foundational support for this model of vmPFC function. Following the initial demonstration that vmPFC damage impairs recall of extinction learning, as evidenced by elevated conditioned fear responses during the extinction period 41, 42, a subsequent electrophysiological study showed

Social Cognition and Self-Relevance

In addition to the substantial collection of results linking vmPFC to value processing, decision making, and emotion regulation (described in the previous two sections), the vmPFC has also been implicated in a number of social cognitive functions relevant for mental illness. For example, patients with vmPFC damage exhibit deficits in empathy 6, 79 and facial emotion recognition 80, 81. Moreover, recent eye-tracking data indicate that vmPFC damage, like amygdala damage, is associated with

Subregions Within the vmPFC and Associations With Psychopathology

Given the variety of psychological functions ascribed to the vmPFC, as well as the variety of brain regions with which the vmPFC interacts, it is important to consider the possibility that there may be anatomically and/or functionally specialized subregions within the vmPFC. To address this possibility empirically, we downloaded a series of meta-analyses of human fMRI data using Neurosynth [www.neurosynth.org; (92)] to identify subregions within vmPFC that are associated with each domain of

Clinical Implications

As described in the preceding sections, the vmPFC has been implicated in a number of social and affective psychological functions relevant for mental illness. In this section we describe several ways that assessments of vmPFC function could potentially impact clinical practice.

Conclusions

Collectively, the findings reviewed in this article substantiate two general points. First, whereas recent review articles highlighting vmPFC dysfunction in mental illness have focused almost exclusively on one psychological function and/or one category of mental illness [e.g., 120, 121, 122, 123], the data reviewed here establish the role of the vmPFC in multiple functions, multiple brain networks, and multiple disorders. Second, there is a burgeoning collection of clinical studies that

Acknowledgments and Disclosures

This work was supported by National Institute of Mental Health Grant No. MH101162 (to MK).

The authors report no biomedical financial interests or potential conflicts of interest.

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

Abstract

Section snippets

Anatomy of the vmPFC

Value and Decision Making

Emotion Regulation

Social Cognition and Self-Relevance

Subregions Within the vmPFC and Associations With Psychopathology

Clinical Implications

Conclusions

Acknowledgments and Disclosures

Trends Neurosci

Cognition

Neuropsychologia

Neuropsychologia

Neurosci Biobehav Rev

Curr Opin Neurobiol

Trends Neurosci

Biol Psychiatry

Neuron

Neuron

Neuron

Neurosci Lett

Neuroscience

Neuroscience

Neuron

Neuron

Biol Psychiatry

Neuron

Neuroscience

Brain Res Bull

Biol Psychol

Neuron

Pain

Behav Brain Res

Biol Psychiatry

Cortex

Cortex

Neurosci Biobehav Rev

Neurosci Biobehav Rev

Neuroimage

Neuropsychologia

Trends Cogn Sci

Exp Neurol

Eur Psychiatry

Architecture and morphology of the human ventromedial prefrontal cortex

Eur J Neurosci

Architectonic subdivision of the human orbital and medial prefrontal cortex

J Comp Neurol

The organization of networks within the orbital and medial prefrontal cortex of rats, monkeys and humans

Cereb Cortex

Severe disturbance of higher cognition after bilateral frontal lobe ablation: Patient EVR

Neurology

Acquired personality disturbances associated with bilateral damage to the ventromedial prefrontal region

Dev Neuropsychol

The involvement of the orbitofrontal cortex in the experience of regret

Science

Ventromedial frontal cortex mediates affective shifting in humans: Evidence from a reversal learning paradigm

Brain

The human ventromedial frontal lobe is critical for learning from negative feedback

Brain

Irrational economic decision-making after ventromedial prefrontal damage: Evidence from the Ultimatum Game

J Neurosci

Economic games quantify diminished sense of guilt in patients with damage to the prefrontal cortex

J Neurosci

Relative reward preference in primate orbitofrontal cortex

Nature

Medial orbitofrontal neurons preferentially signal cues predicting changes in reward during unblocking

J Neurosci

Bilateral orbital prefrontal cortex lesions in rhesus monkeys disrupt choices guided by both reward value and reward contingency

J Neurosci

Separate value comparison and learning mechanisms in macaque medial and lateral orbitofrontal cortex

Proc Natl Acad Sci U S A

Functional connectivity of human striatum: A resting state FMRI study

Cereb Cortex

Functional connectivity and coactivation of the nucleus accumbens: A combined functional connectivity and structure-based meta-analysis

J Cogn Neurosci

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