Measurement and manipulation of oscillatory biomarker of working memory in psychosis

精神病工作记忆振荡生物标志物的测量和操作

• 批准号: 10557835
• 负责人: Molly Erickson
• 金额: $ 55.98万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-05 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10557835
• 关键词: Address; Attention; Award; Biological Markers; Brain; Chronic; Clinical; Cognitive; Cognitive deficits; Coupling; Cues; Data; Development; Effectiveness of Interventions; Electroencephalography; Etiology; Event; Exhibits; Frequencies; Future; Goals; Illness impact; Impaired cognition; Impairment; Individual; Intervention; Learning; Link; Literature; Maintenance; Measurement; Measures; Memory; Memory impairment; National Institute of Mental Health; Participant; Perception; Performance; Persons; Phase; Play; Population; Process; Protocols documentation; Psychophysiology; Psychoses; Psychotic Disorders; Research Personnel; Role; Series; Short-Term Memory; Signal Transduction; Specificity; Training; Validation; Variant; Visual; Work; candidate marker; clinical biomarkers; cognitive ability; design; effective intervention; first episode psychosis; functional disability; improved; memory consolidation; memory process; memory retention; neural; neurobiological mechanism; neurofeedback; novel; peer; personalized intervention; psychotic symptoms; remediation; response; severe mental illness; therapy development

Project Summary Although it is widely known that people with psychosis (PSY) exhibit impairment in a number of cognitive domains—and working memory (WM) in particular—interventions aimed at remediating these deficits have been only modestly successful, and mixed results continue to emerge. One critical barrier to increasing the effectiveness of these interventions is the lack of clarity regarding neurobiological mechanisms that give rise to these impairments, and that can be used as treatment targets for intervention development. We suggest that one reason for this lack of clarity is that WM is frequently studied as a unitary phenomenon, when in fact it is dependent upon several cognitive sub-processes—each of which is supported by a unique neural process, and any one or any set of which may be impaired in PSY. In the present proposal, we will evaluate the role that a promising oscillatory candidate biomarker (alpha desynchronization) plays in constraining WM capacity in PSY. Then, using neurofeedback, we will train participants to modulate this signal and evaluate the impact of this training on visual WM retention. Recently, we and others have demonstrated that robust task-related alpha desynchronization is associated with higher memory capacity among healthy control subjects during a WM task. Furthermore, PSY exhibit robust impairments in this oscillatory process, indicating that it is a strong candidate mechanism by which WM capacity is constrained in this population. However, because a typical WM task is unable to distinguish between the various cognitive sub-processes that support WM, it is not yet known which of these sub- processes is linked to impaired alpha desynchronization in PSY. In the proposed study, we aim to identify the disrupted sub-process that is reflected in impaired alpha desynchronization in PSY (Aim 1), and further evaluate the causal relationship between this brain process and WM storage by manipulating alpha synchronization using neurofeedback (Aim 3). Additionally, we will determine the extent to which impaired alpha desynchronization is specific to psychotic illness, and the degree to which it is impacted by illness chronicity (Aim 2). Finally, in an Exploratory Aim 4, we will also measure a secondary oscillatory biomarker, theta-gamma phase amplitude coupling, which has previously been linked to the maintenance of a memory trace during the delay interval of a WM task. Our overall goal is to clarify the mechanistic role that alpha desynchronization plays in constraining WM capacity in PSY and its impact on downstream neural processes (i.e., theta-gamma phase amplitude coupling), which will lay the groundwork for future development of precision interventions that may effectively target these processes to yield improvements in WM among PSY.

项目摘要 虽然众所周知，精神病患者（PSY）在许多认知功能方面表现出障碍， 领域-特别是工作记忆（WM）-旨在补救这些缺陷的干预措施 目前，这方面的工作仅取得了一定的成功，而且继续出现好坏参半的结果。增加全球化的一个关键障碍是， 这些干预措施的有效性是缺乏明确的神经生物学机制，引起 这些损伤，并可以作为干预发展的治疗目标。我们建议 这种缺乏清晰度的原因之一是，工作记忆经常被当作一种单一的现象来研究，而事实上它是 依赖于几个认知子过程-每个子过程都由一个独特的神经过程支持， 其中任何一个或任何一组可能在PSY中受损。 在本提案中，我们将评估一个有前途的振荡候选生物标志物（α） 在抑制PSY中的WM容量方面起作用。然后，使用神经反馈，我们将训练 参与者调节这个信号，并评估这种训练对视觉WM保持的影响。最近， 我们和其他人已经证明，强大的任务相关的阿尔法去激活与更高的 在WM任务中健康对照受试者的记忆容量。此外，PSY表现出鲁棒性 在这个振荡过程中的损伤，表明这是一个强大的候选机制，WM 这一人群的能力受到限制。然而，由于典型的WM任务无法区分 在支持WM的各种认知子过程之间，目前还不知道这些子过程中的哪一个。 过程与PSY中受损的α去磷酸化有关。 在拟议的研究中，我们的目标是确定受损的阿尔法反映中断的子过程， PSY（目标1）中的去脑化，并进一步评估该大脑过程与 WM存储通过操纵阿尔法同步使用神经反馈（目的3）。此外，我们将 确定受损的α去磷酸化对精神病的特异性程度，以及 它受疾病慢性化的影响（目标2）。最后，在探索性目标4中，我们还将测量 次级振荡生物标志物，θ-γ相位振幅耦合，先前已与 在WM任务的延迟间隔期间维护内存跟踪。 我们的总体目标是阐明α去磷酸化在限制WM中所起的机械作用 PSY中的容量及其对下游神经过程的影响（即，θ-γ相位幅度耦合）， 这将为未来开发精确干预措施奠定基础， 在PSY中产生WM改善的过程。