An EEG Study of Reward Processing and Memory Dysfunction in Schizophrenia

点击翻译按钮获取中文摘要

The overall goal of the proposed project is to improve the care of Veterans with schizophrenia. Deficits in initiating and sustaining goal-oriented behavior, termed avolition, is a hallmark feature of schizophrenia that has cascading effects on interpersonal relationships, occupational functioning, and psychological well-being. There is widespread consensus that adequate interventions for avolition do not exist. The development of effective and tailored interventions for avolition depends on a clearer understanding of its neurobiological underpinnings in concert with translational models that bridge with pre-clinical research. Recent models have posited several mechanisms that contribute to avolition, including failures to sufficiently recall past personal experiences when imagining and evaluating future gains, reduced capacity to anticipate reward from future outcomes, and indecision when preparing movements towards a goal. To date, there has been no thorough test of how these various processes contribute to avolition in the context of schizophrenia. Animal models of goal pursuit show that core brain rhythms orchestrate memory and reward functioning; similar oscillatory patterns support memory and reward processing in humans and are often deficient in schizophrenia. Taken together, avolition in schizophrenia could arise, in part, from neural oscillatory signals that can be compared to preclinical models. Noninvasive neurostimulation methods are a safe and promising avenue to try to augment these oscillatory signals in Veterans with schizophrenia, in an effort to reduce avolition. Mounting evidence shows that stimulation applied to a novel episodic memory-related brain target enhances memory in healthy individuals. Whether targeting this same region remediates memory-related oscillatory deficits in schizophrenia, and corresponding behavioral sequalae, is unknown. This proposal aims to address these gaps in the literature by isolating a set of mechanisms related to avolition, and by testing whether a single session of transient, noninvasive neurostimulation can augment the neural signals associated with these mechanisms in Veterans with schizophrenia. This study will combine electroencephalography (EEG) recordings and theta burst stimulation (TBS), a noninvasive neurostimulation method, to achieve three specific aims: 1) to investigate the contributions of episodic memory, reward anticipation, and motor preparation processes in the prediction of clinical avolition in schizophrenia using a translational reward task; 2) to identify episodic-memory neural oscillatory deficits in Veterans with schizophrenia using EEG, and evaluate relationships between oscillatory dysfunction with reward anticipation, motor preparation, and clinical avolition; and finally, 3) to examine whether memory-related oscillatory activity in Veterans with schizophrenia can be enhanced with a brief TBS protocol applied to a novel memory-related brain target. The proposed work will leverage the temporal precision of EEG and the efficiency of TBS. Knowledge gained from this study could provide important insights into the pathophysiology of schizophrenia. In turn, these findings could facilitate the identification of neurophysiological targets for novel interventions specifically aimed at ameliorating avolition, thereby improving functional outcomes in Veterans with schizophrenia.