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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

基本信息

批准号：
10793826
负责人：
Fiza Singh
金额：
$ 30.76万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2023-12-31
项目状态：
已结题

项目摘要

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.

摘要精神分裂症（SCZ）是一种慢性衰弱性精神障碍，影响240万美国人，这将导致相当大的个人和社会成本。在SCZ患者中，认知缺陷（CD）发生在疾病的过程，与更严重的疾病有关，是功能性疾病的最佳预测因子。结果。尽管如此，迄今为止，CD一直难以使用可用的治疗方法治疗。最近的研究提示SCZ患者的CD可能是由分布式神经网络的异常同步引起的。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中，国家依赖的方式。因此，改善异常神经同步的新疗法可能会改善以前难治的症状由紊乱的大脑网络引起。神经同步性或伽马波段（GBR，30 - 45 Hz）的相干性在自上而下的神经系统中起着核心作用。注意、多感觉加工、知觉联结和工作记忆。SCZ患者表现出 GBR异常，并且损害的程度与认知紊乱的严重程度相关。鉴于这些结果，改善GBR应改善CD，包括SCZ中的WM。这一假设一直被通过重复经颅磁刺激（rTMS）进行测试和确认。此外，基于EEG 神经反馈（NFB）被假设为改善SCZ患者的GBR和认知功能。NFB是低成本，易于管理和耐受性良好的治疗。在健康对照组中，Gamma-NFB可改善GBR 和认知功能，包括WM。因此，我们建议测试改进的可行性和有效性，在使用R61/R33机制框架的SCZ患者中使用γ-NFB的GBR。第一项试验（R61）是一项概念验证研究，旨在评估靶点参与和剂量响应曲线24名SCZ患者将接受为期12周的G-NFB训练（每周2次， 30分钟持续时间），并评估1）训练证据，2）GBR变化，3）WM变化和4）社区功能的变化。第二次试验（R33）旨在确认基于训练的目标接合从R61获得的参数，并评估G-NFB是否优于活性安慰剂神经反馈干预改善GBR、WM和社区功能。