Measurement and manipulation of oscillatory biomarker of working memory in psychosis

项目摘要 尽管众所周知，精神病患者(PSY)在许多认知能力方面表现出障碍 领域--尤其是工作记忆(WM)--旨在弥补这些缺陷的干预措施 只取得了一定的成功，结果喜忧参半。增加经济增长的一个关键障碍 这些干预措施的有效性在于缺乏对引起以下疾病的神经生物学机制的了解 这些损害，可以作为干预发展的治疗目标。我们建议 这种缺乏清晰度的一个原因是，工作记忆经常被作为一种单一现象来研究，而实际上它是 依赖于几个认知子过程-每个子过程都有一个独特的神经过程支持，以及 其中任何一项或任何一组可能在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记物(阿尔法)的作用 去同步)在限制PSY中的WM容量方面发挥作用。然后，使用神经反馈，我们将训练 参与者调节这一信号，并评估这一培训对视觉WM保持的影响。最近， 我们和其他人已经证明，健壮的任务相关的阿尔法去同步化与更高的 健康对照组受试者在工作记忆任务中的记忆容量。此外，PSY表现出健壮性 这一振荡过程中的损伤，表明它是WM 在这个群体中，容量是有限的。然而，因为典型的工作流管理任务无法区分 在支持工作记忆的各种认知子过程之间，尚不清楚这些子过程中的哪一个。 进程与PSY中受损的阿尔法去同步化有关。 在拟议的研究中，我们的目标是确定反映在阿尔法受损中的受扰子过程 PSY中的去同步化(目标1)，并进一步评估这一脑过程与 通过使用神经反馈操纵阿尔法同步来存储WM(目标3)。此外，我们还将 确定阿尔法去同步化受损的程度是精神病所特有的，以及程度 它受到慢性病的影响(目标2)。最后，在探索性目标4中，我们还将测量 次级振荡生物标记物，theta-Gamma相幅耦合，以前曾被联系到 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阿尔法去同步化在约束WM中所起的机械性作用 PSY的容量及其对下游神经过程的影响(即，θ-伽马相位幅度耦合)， 这将为未来精确干预的发展奠定基础，这些干预可能有效地针对这些 在PSY中产生WM改进的过程。

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.