The Neural Basis of the Positivity Offset as a Mechanism of Avolition in Schizophrenia

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PROJECT SUMMARY Avolition (e.g., reduced motivation and engagement in goal-directed behavior) is a core negative symptom and one of the strongest predictors of functional disability in schizophrenia. Current psychosocial and pharmacological interventions are ineffective at treating avolition, largely due to limited understanding of its underlying mechanisms. Leading conceptual frameworks implicating dysfunctional cortico-striatal interactions and abnormalities in reward processing have improved the field's understanding of the etiological underpinnings of avolition; however, this work has not yet led to significant breakthroughs in treatment. These models assume that the hedonic response is intact in schizophrenia, a theory our lab recently proposed may be premature. By applying an affective science approach informed by Cacioppo's Evaluative Space Model of Emotional Experience, we recently demonstrated that abnormalities in emotional experience do contribute to avolition in schizophrenia, in the form of a reduction in the positivity offset. The positivity offset is an adaptive function characterized by a greater balance of positive than negative emotion at low levels of arousal, which promotes motivated behaviors. Preliminary data from our lab indicates that the positivity offset is reduced in schizophrenia and is associated with clinically rated negative symptoms, suggesting it may offer a novel explanation for avolition. In the current study, we aim to expand these findings by: 1) identifying the neural circuits underlying the positivity offset, 2) determining whether the positivity offset is also reduced in the real- world in schizophrenia, and 3) determining whether reductions in the positivity offset and associated neural processes predict avolition in everyday life. Specifically, we will use fMRI to measure neural activity during an emotional experience task to test the hypothesis that reduced activation of the medial prefrontal cortex, nucleus accumbens, and caudate nucleus is associated with reductions in the positivity offset in schizophrenia. Additionally, we will examine whether activation in these regions predicts positivity offset reduction and avolition in the real-world, which will be measured via active and passive digital phenotyping. This approach addresses the gap in understanding of the affective and neural mechanisms underlying avolition and their impact on daily functioning. Findings have potential to inform personalized medicine approaches to treating avolition by identifying specific neural circuits and affective processes that can serve as treatment targets for pharmacological and psychosocial interventions. Further, few clinical investigators are trained to adopt a transdisciplinary, multimodal approach to study negative symptoms. The proposed research and training plans are designed to meet this urgent need in the field, providing the applicant with skills in cutting-edge neuroimaging and digital phenotyping methods to test hypotheses about the origins of avolition.