The Neurobiology of Emotional Experience in Patients with Schizophrenia: Using Investigations of Odor Valence Perception to Understand the Emotion Paradox

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Emotional deficits such as flat affect and anhedonia are core features of schizophrenia, but self-report from patients suggests that this reduced outward expression of emotional reactivity is paradoxically often accompanied by increased internal emotional experience. Behavioral studies suggest that this may be caused by positive and negative symptoms selectively affecting different parts of the valence spectrum of emotional stimuli. The neural processes underlying these observations are, however, to date poorly understood. Recent work in healthy control subjects emphasizes the existence of multiple input paths to the amygdala. The combination of neural input from these different networks is thought to modulate the amygdala response to emotional stimuli. The proposed project will investigate the relative contribution of these pathways to abnormal amygdala activation to emotional stimuli across valence and arousal dimensions in schizophrenia, and how this interplay is affected by illness characteristics. As a first step, we propose to design an odor battery which systematically varies stimulus intensity and valence across the entire affective space, and carefully validate this battery in healthy control subjects. This battery will then be used to behaviorally assess relationships between odor valence perception and illness characteristics and, using functional magnetic resonance imaging, characterize intact and disturbed relationships among the neural networks representing emotional value. In particular, the goal is to dissociate the contribution of a prefrontal network of DLPFC, ACC and OFC, supposedly subserving downregulation of a negative emotional response, and the reward network, including ventral striatum and nucleus accumbens. The aim of the project is to build a theoretical foundation for symptom-based intervention for emotional deficits, based on specific illness characteristics that a patient presents with.