PROJECT SUMMARY Anhedonia is a common psychological symptom, of which the pathophysiological mechanisms are not clearly understood. Moreover, anhedonia is a particularly difficult symptom to treat. The identification of underlying mechanisms is therefore critical. Two core features of anhedonia are reduced motivation and impaired reinforcement learning (RL). To date, however, these two components of anhedonia have been largely studied in isolation. This is somewhat surprising, as both motivation and RL are known to engage a common network of neural substrates, including the ventral striatum, mesolimbic dopamine, and the dorsal anterior cingulate (dACC). Indeed, one proposed mechanism by which both motivational and RL deficits may arise is an abnormal neural encoding of prediction error (PE), a signal with which the brain updates expectations about the value of future outcomes. Specifically, disruptions in PE signals may lead to inappropriate updating and underestimation of the value of effortful actions, thereby leading to reduced motivation. Therefore, the goal of this proposal is to test the hypothesis that disrupted PE signaling may impact motivated behavior. A key limitation of prior work in this area is that traditional behavioral paradigms assessing motivated behaviors have used simplistic and rigid trial-by- trial structures that do not capture critical elements of motivated actions. Indeed, in lived experience, motivation towards a goal emerges from a series of moment-by-moment decisions that occur as one interacts with the environment. Therefore, more naturalistic paradigms and methods are needed. The PI will fill this gap in two ways, by 1) examining the causal effect of disrupting PE signaling during a novel virtual-reality based paradigm using inhibitory single-pulse transcranial magnetic stimulation to the dACC, and 2) testing the effects of a behavioral manipulation of PE on motivation to engage in physical exercise in a two-week ecological momentary assessment paradigm. This work is innovative because it uses novel, ecologically-valid approaches to study motivated behavior and to causally-validate a specific neural mechanism for the integration of PE signals and motivated actions. The significance of this work is that the role of PE signals in shaping motivated behaviors could serve as a key mechanism underlying anhedonic symptoms, and a better understanding of its neural circuitry could aid the future development of mechanism-based treatments for anhedonia. The PI has assembled an interdisciplinary team that will help him to gain expertise in the neurobiology of anhedonia and advanced computational modeling of human behavior. This project represents an excellent opportunity for the PI to develop intellectually and professionally as an independent researcher.