Cross-frequency coupling and cognition in early psychosis

早期精神病的跨频耦合和认知

• 批准号: 8681789
• 负责人: RAYMOND Y CHO
• 金额: $ 19.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681789
• 关键词: Accounting; Address; Anatomy; Attenuated; Auditory; Automobile Driving; Behavior; Biological Markers; Brain; Chronic Disease; Cognition; Cognitive; Computer Simulation; Coupling; Diagnostic Specificity; Electroencephalography; Frequencies; Functional disorder; Future; High Frequency Oscillation; Impaired cognition; Impairment; Interneuron function; Interneurons; Investigation; Lead; Lesion; Magnetoencephalography; Membrane; Modeling; Neurons; Patients; Performance; Pharmaceutical Preparations; Phase; Population Study; Prefrontal Cortex; Process; Psychotic Disorders; Research; Research Domain Criteria; Resolution; Role; Scalp structure; Schizophrenia; Sensory; Services; Short-Term Memory; Signal Transduction; Specificity; Study models; Testing; Tissues; Work; base; cell type; cognitive enhancement; cognitive function; computer studies; cranium; gamma-Aminobutyric Acid; indexing; insight; neuromechanism; new therapeutic target; novel; public health relevance; response; sensory cortex

DESCRIPTION (provided by applicant): Disturbances in cortical oscillations are thought to be core to the pathophysiology of sensory and cognitive processing impairments in schizophrenia, with impairments in the gamma-band (30-100 Hz) as well as lower frequency-bands such as theta (4-8 Hz) and alpha (8-12 Hz). There is growing evidence that modulation of gamma by lower frequency bands is also critical for normal sensory and cognitive processing. Accordingly, restoring gamma activity may be necessary but not sufficient for restoring cognitive function, which requires the organizing influence by lower frequency modulations. While such cross-frequency coupling (CFC) is thought to be a core neurocomputational mechanism for regulating gamma oscillations in the service of cognition, CFC has been largely ignored in in schizophrenia research. The current project aims to address this important gap by conducting the first systematic investigation of CFC disturbances in schizophrenia employing an integrated magnetoencephalography (MEG) and computational modeling approach. Investigations of CFC most commonly examine phase-amplitude coupling, reflecting lower frequency changes in membrane excitability that systematically modulates the amplitude of higher frequency oscillations of the local network. Preliminary studies show evidence of disturbances in such phase-amplitude coupling in schizophrenia. Patients performing the auditory steady-state response (ASSR) task, a sensory cortical periodic driving paradigm, showed impaired alpha-gamma coupling compared to controls. Preliminary findings also show prefrontal cortical theta-gamma CFC in healthy controls during working memory performance with strong correlations with working memory capacity, demonstrating feasibility for investigating CFC disturbances in schizophrenia patients. Finally, preliminary computational work modeled post-mortem findings of disturbances in fast-spiking interneurons (FSI) as 'lesions' to the model FSI, reproducing disturbances in alpha-gamma CFC. Given these findings, we hypothesize that sensory and prefrontal cortical CFC will be disturbed in schizophrenia and that FSI disturbances are sufficient to provide a mechanistic account of CFC disturbances. These hypotheses will be addressed through the following Specific Aims: (1) To investigate sensory cortical CFC disturbances in early psychosis; (2) To investigate prefrontal cortical CFC disturbances in early psychosis; and (3) To investigate neurocomputational mechanisms of CFC disturbance in early psychosis. We anticipate that this study in early psychosis will reveal disturbances in CFC, a critical organizing mechanism for neural activity underlying sensory and cognitive processing. Together, the findings of this project will provide a novel empirical and theoretical framework for future studies that will aim to pharmacologically target specific components of cortical circuitry o enhance CFC and cognition in schizophrenia.

描述（由申请人提供）：皮层振荡的干扰被认为是精神分裂症患者感觉和认知加工障碍病理生理学的核心，包括γ波段（30- 100hz）以及较低频率波段(如theta （4- 8hz）和alpha （8- 12hz）的损伤。越来越多的证据表明，较低频段的伽马调制对正常的感觉和认知处理也至关重要。因此，恢复伽马活动可能是必要的，但不足以恢复认知功能，这需要低频调制的组织影响。虽然这种交叉频率耦合（CFC）被认为是调节伽马振荡以服务于认知的核心神经计算机制，但在精神分裂症的研究中，CFC在很大程度上被忽视。目前的项目旨在通过采用综合脑磁图（MEG）和计算建模方法对精神分裂症患者的CFC干扰进行首次系统调查，以解决这一重要差距。对CFC的研究通常检查相幅耦合，反映膜兴奋性的低频变化，系统地调节局部网络的高频振荡幅度。初步研究表明，精神分裂症患者存在这种相幅耦合障碍。与对照组相比，执行听觉稳态反应（ASSR）任务（一种感觉皮层周期性驱动范式）的患者表现出α - γ耦合受损。初步研究结果还显示，健康对照在工作记忆表现期间前额叶皮层θ - γ CFC与工作记忆容量有很强的相关性，证明了研究精神分裂症患者CFC障碍的可行性。最后，初步的计算工作将死后发现的快速尖峰中间神经元（FSI）的干扰作为模型FSI的“损伤”，再现了α - γ CFC的干扰。鉴于这些发现，我们假设精神分裂症患者的感觉和前额叶皮质CFC会受到干扰，而FSI干扰足以提供CFC干扰的机制解释。这些假设将通过以下具体目的来解决：(1)研究早期精神病的感觉皮质CFC障碍；(2)探讨早期精神病患者前额皮质CFC障碍；(3)探讨早期精神病患者CFC障碍的神经计算机制。我们预计这项研究在早期精神病将揭示CFC的障碍，CFC是一个重要的神经活动组织机制，在感觉和认知加工基础上。总之，这个项目的发现将提供一个新的实证和理论框架