An EEG Study of Reward Processing and Memory Dysfunction in Schizophrenia

拟议项目的总体目标是改善对精神分裂症退伍军人的护理。赤字 在发起和维持以目标为导向的行为时，称为自我陶醉是精神分裂症的一个显著特征 对人际关系、职业功能和心理健康有连锁影响。 人们普遍认为，不存在对撕裂行为进行适当干预的情况。的发展。 有效的、量身定做的治疗方法依赖于对其神经生物学的更清楚的了解。 与转换模型协调一致的基础，架起了与临床前研究之间的桥梁。最近的型号已经 提出了几种导致遗弃的机制，包括未能充分回忆过去的个人经历 想象和评估未来收益时的体验，降低了预期未来回报的能力 结果，以及在准备朝着目标前进时的优柔寡断。到目前为止，还没有彻底的 在精神分裂症的情况下，测试这些不同的过程是如何促进情感分离的。大鼠的动物模型 目标追求表明，核心大脑节律协调记忆和奖励功能；类似的振荡 模式支持人类的记忆和奖赏处理，而精神分裂症患者往往缺乏这种模式。已被占用 总而言之，精神分裂症患者的精神分裂可能部分源于神经振荡信号，这种信号可以与 临床前模型。非侵入性神经刺激方法是一种安全和有前景的方法，试图增强 这些振荡信号在患有精神分裂症的退伍军人身上，以努力减少撕裂。越来越多的证据 显示刺激一种新的与情节记忆相关的大脑靶点可增强健康人的记忆 个人。靶向相同的区域是否可以修复记忆相关的振荡缺陷 精神分裂症和相应的行为后遗症尚不清楚。 该建议旨在通过隔离一组与以下各项相关的机制来解决文献中的这些空白 通过测试一次短暂的、非侵入性的神经刺激是否可以增加 患有精神分裂症的退伍军人中与这些机制相关的神经信号。这项研究将结合 脑电记录与非侵入性神经刺激--爆发性刺激(TBS) 方法，实现三个具体目标：1)考察情景记忆、奖赏的贡献 预测和运动准备过程在预测精神分裂症临床行为中的作用 翻译奖赏任务；2)识别退伍军人的情景记忆神经振荡缺陷 对精神分裂症患者进行脑电检查，并评估振荡功能障碍与奖励预期之间的关系， 运动准备和临床活动；最后，3)检查记忆相关的振荡活动 在患有精神分裂症的退伍军人中，可以通过应用一种新的记忆相关的简短TBS方案来增强 大脑目标。所提出的工作将平衡脑电的时间精度和TBS的效率。 从这项研究中获得的知识可以为研究糖尿病的病理生理学提供重要的见解。 精神分裂症。反过来，这些发现可以帮助识别新的神经生理靶点。 旨在改善伤残，从而改善退伍军人功能结果的干预措施 患有精神分裂症。

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.