Neural Dynamics of Frustrative Nonreward: Bridging Irritability and Depression Vulnerability

We often face situations in which our goals, expectations, or desires are not met. Such experiences can elicit an aversive emotional state of frustration, known as frustrative nonreward (FNR). Heightened sensitivity to FNR is considered a core underlying mechanism of irritability, a transdiagnostic symptom particularly prevalent in depression. However, the neural and behavioral effects of FNR in humans, and their potential role in depression vulnerability, remain poorly understood. This thesis investigates neural responses to FNR-inducing events, focusing on midfrontal theta power, a signal generated in the anterior cingulate cortex and implicated in cognitive control. It examines whether this signal predicts subsequent adjustments in behavior, and how subjective frustration influences these brain-behavior dynamics. In addition, it assesses how irritability and anhedonia, often co-occurring in depression, jointly influence reward functioning, in order to identify mechanisms linking irritability to depression. Across five experimental studies combining electroencephalography, computational modeling, and network analysis, this thesis shows that, while FNR induces adaptive behavioral adjustments supported by midfrontal theta control signals, elevated subjective frustration may reduce the effective implementation of cognitive control and the execution of effortful behavior. The findings further identify reduced motivational engagement as a candidate reward-related dimension linking irritability to depression. Building on these findings, I propose a novel, testable mechanistic pathway in which heightened FNR sensitivity may reduce engagement and persistence in effortful goal-directed behavior, potentially increasing vulnerability to the motivational impairments observed in depression.