An EEG Study of Reward Processing and Memory Dysfunction in Schizophrenia

精神分裂症奖励加工和记忆功能障碍的脑电图研究

• 批准号: 10657340
• 负责人: Samantha Abram
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10657340
• 关键词: Address; Advanced Development; Animal Model; Area; Behavior; Behavioral; Brain; Caring; Chronic Disease; Clinical; Clip; Consensus; Development; Disease; Electroencephalography; Episodic memory; Equipment and supply inventories; Event-Related Potentials; Exhibits; Failure; Frequencies; Functional disorder; Funding; Future; Goals; Hand; Health Care Costs; Healthcare; Hippocampus; Human; Individual; Internet; Interpersonal Relations; Intervention; Investigation; Knowledge; Lateral; Literature; Measures; Mediating; Memory; Memory impairment; Methods; Modeling; Motor; Movement; Network-based; Neurobiology; Neurosciences; Occupational; Outcome; Parietal Lobe; Participant; Patients; Pattern; Persons; Phase; Pre-Clinical Model; Prediction of Response to Therapy; Preparation; Process; Protocols documentation; Psychoses; Rattus; Reaction Time; Research; Research Personnel; Resistance; Retrieval; Rewards; Rodent; Role; Schizophrenia; Signal Transduction; Symptoms; Test Result; Testing; Time; Transcranial magnetic stimulation; Translating; Veterans; Well in self; Work; clinical predictors; cognitive function; design; disability; disabling symptom; effective intervention; experience; functional improvement; goal oriented behavior; improved; insight; memory process; mental representation; motor deficit; multimodality; neural; neurophysiology; neurotransmission; novel; personalized medicine; positive emotional state; pre-clinical research; programs; psychotic; remediation; response; reward anticipation; reward processing; social; success; tool; training opportunity; translation to humans; translational model

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.

拟议项目的总体目标是改善精神分裂症退伍军人的护理。赤字 在启动和维持目标导向的行为，称为逃避，是精神分裂症的标志性特征， 对人际关系、职业功能和心理健康产生连锁效应。 人们普遍认为，不存在充分的干预措施。的发展 有效和量身定制的干预依赖于更清楚地了解其神经生物学 与临床前研究衔接的转化模型相一致的基础。最近的模型有 假设了几种有助于避免的机制，包括无法充分回忆过去的个人经历， 想象和评估未来收益时的经验，减少对未来回报的预期能力 结果，以及在准备朝着目标前进时的犹豫不决。到目前为止，还没有彻底的 在精神分裂症的背景下，这些不同的过程如何有助于意志的测试。动物模型 目标追求表明，核心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励处理，并且通常在精神分裂症中缺乏。采取 总之，精神分裂症中的意志丧失可能部分来自神经振荡信号， 临床前模型。无创神经刺激方法是一种安全且有前途的方法， 这些振荡信号在退伍军人精神分裂症，在努力减少avolition。越来越多的证据 表明，刺激施加到一个新的情节记忆相关的大脑目标增强记忆健康 个体是否针对同一区域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是未知的。 本提案旨在通过分离一套与以下方面有关的机制来填补文献中的这些空白： 通过测试单次短暂的非侵入性神经刺激是否可以增强 与这些机制相关的神经信号。本研究将联合收割机 脑电图（EEG）记录和θ波群刺激（TBS），一种非侵入性神经刺激 方法，达到三个具体目标：1）探讨情景记忆，奖励的贡献， 预测精神分裂症患者的临床自主性的运动准备过程 翻译奖励任务; 2）识别退伍军人的情景记忆神经振荡缺陷， 精神分裂症使用脑电图，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avolition;最后，3）检查是否与记忆有关的振荡活动 在退伍军人精神分裂症可以加强与一个简短的TBS协议适用于一个新的记忆相关的 大脑目标所提出的工作将利用EEG的时间精度和TBS的效率。 从这项研究中获得的知识可以提供重要的见解， 精神分裂症反过来，这些发现可以促进新的神经生理学靶点的识别。 专门针对改善排尿的干预措施，从而改善退伍军人的功能结局 精神分裂症