Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward.

unlabelledThe ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the "reward circuit" of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making. SIGNIFICANCE STATEMENT: Maladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited "reward circuit," the ventral striatum and the ventromedial prefrontal cortex (vmPFC). For the first time in humans, we demonstrate that damage to the vmPFC results in decreased ventral striatum activity during reward anticipation. These data provide unique evidence on the causal mechanisms by which the vmPFC and ventral striatum interact during the anticipation of rewards.