Title: Action monitoring in depression
Description: The heterogeneity of Major Depressive Disorder (MDD) presents important challenges, and suggests that this debilitating disorder likely encompasses multiple conditions with distinct etiologies. To address this issue, the current studies investigated behavioral and neural manifestations of circumscribed executive dysfunctions--specifically action monitoring dysfunction emerging in situations requiring adaptive adjustments following response conflict or perceived failure--and how these processes might be further affected by incentives. Owing to the role of anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC) regions in action monitoring, executive impairments in individuals with MDD or at increased genetic risk for MDD were hypothesized to be associated with dysfunctions within frontocingulate pathways. In Studies 1 and 2, event-related potentials (ERPs) were recorded as controls and MDD subjects performed a Stroop task with (Study 2) and without (Study 1) monetary incentives. In Study 3, to investigate potential action monitoring deficits in individuals at increased risk for MDD, molecular genetic and functional magnetic resonance imaging (fMRI) data were collected from psychiatrically healthy participants performing a Flanker task. Based on prior findings, we hypothesized that, relative to controls, MDD subjects would show (1) action monitoring deficits (e.g., reduced accuracy in trials with increased response conflict or following errors); (2) abnormal error-related ERP markers, particularly under conditions of increased incentive motivation; and (3) dysfunctional ACC activation in response to errors and increased response conflict.

Moreover, we hypothesized that similar action monitoring impairments and ACC dysfunctions would emerge in individuals carrying genetic variants previously associated with increased risk for depression (5-HTTLPR). Findings from Studies 1 and 3 confirmed action monitoring deficits in individuals with or at risk for MDD. These deficits were associated with hyperactive rostral ACC responses to errors, hypoactive dorsal ACC responses during response conflict, and impaired DLPFC recruitment following errors (Studies 1 & 3). Additionally, when monetary rewards were available, MDD subjects exhibited blunted responses at stages assumed to index conscious error awareness and subjective affective evaluative response (Study 2). Together, these data indicate that impaired action monitoring and associated ACC dysregulation may represent a risk factors associated with increased vulnerability to depression.