Impaired Valuation Leads to Increased Apathy Following Ventromedial Prefrontal Cortex Damage

Apathy is defined by reduced goal-directed behavior, and is common in patients with damage to the ventromedial prefrontal cortex (vmPFC). Separately, in neuroeconomics research, the vmPFC has been shown to play a role in reward processing-namely, in "stimulus valuation," or the computation of the subjective reward value of a stimulus. Here, we used a sample of patients with focal brain lesions (N = 93) and matched healthy controls (N = 21) to determine whether the association between vmPFC damage and increased apathy is driven by impaired valuation. An auction task was used to measure valuation, and apathy was assessed via caregiver ratings of patients' day-to-day behavior. Lesion-symptom mapping identified the locus of impaired valuation in the vmPFC, and patients with damage to this region demonstrated increased apathy relative to patients with damage to dorsomedial prefrontal cortex (dmPFC), patients with damage to other brain regions, and healthy controls. Critically, the association between vmPFC damage and apathy was mediated by impaired valuation, with no effect as a function of dmPFC damage. Our results implicate a valuation-based mechanism underlying the relationship between vmPFC integrity and apathy, bridging findings from both the clinical literature and neuroeconomics research.