Enhancing Gamma Band Response in Schizophrenia to Improve Working Memory

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)的神经同步性或一致性在自上而下起着核心作用 注意、多感觉加工、知觉绑定和工作记忆(WM)。患有SCZ的患者表现出 GBR异常，损伤的程度与认知障碍的严重程度相关。 鉴于这些结果，改善GBR应该会改善CD，包括SCZ的WM。这一假设一直是 使用重复经颅磁刺激(RTMS)进行测试和确认。此外，基于脑电的 神经反馈(NFB)被认为可以改善SCZ患者的GBR和认知功能。NFB是一种 治疗成本低，使用方便，耐受性好。在健康对照组中，Gamma-NFB改善GBR 以及包括WM在内的认知功能。因此，我们建议测试改进的可行性和有效性 GBR使用伽马-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。24名SCZ患者将接受为期12周的G-NFB训练(每周2次 30分钟)，并评估1)训练的证据，2)GBR的变化，3)WM的变化和4) 社区功能的变化。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。

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 or coherence 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. Twenty-four SCZ patients will receive G-NFB training for 12 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.