Enhancing Gamma Band Response in Schizophrenia to Improve Working Memory

增强精神分裂症患者的伽马带反应以改善工作记忆

• 批准号: 9817085
• 负责人: Fiza Singh
• 金额: $ 9.76万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-12 至 2020-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9817085
• 关键词: Affect; Aftercare; American; Area; Attention; Base of the Brain; Binding; Brain Diseases; Chronic; Cognitive; Cognitive deficits; Communities; Computers; Data; Dose; Double-Blind Method; Effectiveness; Electroencephalography; Exhibits; Hour; Impairment; Independent Living; Individual; Intervention; Measurement; Measures; Mediating; Mediator of activation protein; Mental disorders; Neurons; Outcome; Patients; Phase; Pilot Projects; Placebos; Play; Protocols documentation; Randomized; Refractory; Research Design; Role; Schizophrenia; Severities; Short-Term Memory; Surveys; Symptoms; Testing; Time; Training; Work; base; cognitive function; cost; economic impact; functional outcomes; improved; multisensory; neural network; neurofeedback; new therapeutic target; novel; novel therapeutics; open label; primary outcome; relating to nervous system; repetitive transcranial magnetic stimulation; response; secondary outcome; skills; societal costs

ABSTRACT Schizophrenia (SCZ) is a chronic debilitating mental disorder that affects 2.4 million Americans and leads to considerable individual and societal costs. In patients with SCZ, cognitive deficits (CD) occur early in the course of the illness, are associated with more severe illness, and are the best predictor of functional outcomes. Nonetheless, to date, CD have been difficult to treat using available treatments. Recent studies suggest CD in patients with SCZ may arise from abnormal synchronization of distributed neural networks. Synchronization or synchronous firing of neurons, binds cortical areas into functional networks in a task and state-dependent manner. Thus novel therapies that improve abnormal neural synchrony may improve previously refractory symptoms arising from disordered brain networks. Neural synchrony in the gamma band (GBR, 30-45Hz) plays a central role in top-down attention, multisensory processing, perceptual binding and working memory (WM). Patients with SCZ exhibit abnormal GBR, and the magnitude of impairment is associated with the severity of cognitive disorganization. Given these results, improving GBR should improve CD, including WM in SCZ. This hypothesis has been tested and confirmed using repetitive transcranial magnetic stimulation (rTMS). Additionally, EEG-based neurofeedback (NFB) is hypothesized to improve GBR and cognitive function in patients with SCZ. NFB is a low-cost, easily administered and well-tolerated treatment. In healthy controls, Gamma-NFB improves GBR and cognitive function including WM. Thus, we propose testing the feasibility and effectiveness of improving GBR using gamma-NFB in patients with SCZ using the framework of the R61/R33 mechanism. The first trial (R61) is a proof-of-concept study designed to assess target engagement and dose response curve. Thirty SCZ patients will receive G-NFB training for 20 weeks (2 weekly sessions of 30minute duration) and be assessed for 1) evidence of training, 2) Change in GBR, 3) Change in WM and 4) Change in community functioning. The second trial (R33) aims to confirm target engagement based on training parameters obtained from R61, and to assess whether G-NFB is superior to an active-placebo neurofeedback intervention in improving GBR, WM and community functioning.

摘要 精神分裂症(SCZ)是一种慢性衰弱精神疾病，影响着240万美国人和 导致了相当大的个人和社会成本。在SCZ患者中，认知障碍(CD)发生在 病程与更严重的疾病相关，并且是功能性的最佳预测因子 结果。尽管如此，到目前为止，CD一直很难使用现有的治疗方法进行治疗。最新研究 提示SCZ患者的CD可能与分布神经网络的异常同步性有关。 神经元的同步或同步放电，将皮层区域绑定到任务中的功能网络，并 依赖国家的方式。因此，改善异常神经同步性的新疗法可能会得到改善 以前顽固的症状是由大脑网络紊乱引起的。 伽马频段(GBR，30-45赫兹)的神经同步性在自上而下的注意中起着核心作用， 多感觉加工、知觉绑定和工作记忆。SCZ患者表现出异常 GBR，损伤的程度与认知障碍的严重程度相关。考虑到这些 结果，改善GBR应改善CD，包括SCZ的WM。这一假设已经过检验，而且 经重复经颅磁刺激(RTMS)确诊。此外，基于脑电的神经反馈 (NFB)被假设为改善SCZ患者的GBR和认知功能。NFB是一种低成本、简单的 管理和耐受性良好的治疗。在健康对照组中，Gamma-NFB改善GBR和认知能力 功能包括WM。因此，我们建议测试改进GBR的可行性和有效性 γ-NFB在SCZ患者中使用R61/R33机制的框架。 第一个试验(R61)是一项概念验证研究，旨在评估目标参与度和剂量 响应曲线。30名SCZ患者将接受为期20周的G-NFB训练(每周2次，每次30分钟 持续时间)和评估1)训练证据，2)GBR的变化，3)WM的变化和4) 社区运作。第二个试验(R33)旨在基于培训确认目标参与度 从R61获得的参数，并评估G-NFB是否优于积极的安慰剂神经反馈 改善GBR、WM和社区功能的干预。