Enhancing gamma band response to improve working memory in individuals with mild cognitive impairment

摘要 阿尔茨海默病是一种神经退行性疾病的临床表现，其特征是 普遍进行性认知功能减退，日常生活能力受损。根据 美国疾病控制中心阿尔茨海默氏症或痴呆症患者将增至13.9人 到2060年将达到100万(2018年报告)，使其成为公众迫切关注的问题。在过去的十年里，研究集中在 早期发现了这种疾病，并在出现功能障碍之前发现了一个前驱症状阶段， 称为轻度认知障碍(MCI)。尽管早期发现，但几乎没有治疗方案可以延缓 从MCI下降到AD。最近的研究表明，认知缺陷可能是由异常引起的 分布式神经网络的同步。 神经元的同步或同步放电，在任务中将皮质区域绑定到功能网络 和国家依赖的方式。具体地说，伽马频段(30-45赫兹)的神经同步性起着核心作用 健康人自上而下注意、多感觉加工、知觉绑定和工作记忆的研究 个人。患有AD谱系障碍的个体和动物的伽马频段反应(GBR)受损 针对GBR的AD模型的研究表明，对认知有积极影响。因此，发展类似的 针对GBR的治疗有望改善MCI患者的认知能力。我们的团队已经 对SCZ患者实施针对GBR的脑电-神经反馈(EEG-NFB)治疗，早期结果令人鼓舞 (研究策略)。NFB是一种低成本、安全、易于管理的闭环神经调节技术， 受试者的大脑活动被显示为视觉隐喻，并被要求将其调整到给定的方向。脑电波- NFB已被用于从ADHD、抑郁症到焦虑症的多种疾病以及多发性 包括儿童和老年人在内的人群。基于这些令人鼓舞的结果，我们提议进行一项研究 为了1)测试EEG-NFB靶向GBR在遗忘性MCI患者中的疗效与 假/安慰剂，2)探索认知变化的潜在机制，3)探索预治疗 预测治疗反应的特征。

Abstract Alzheimer’s disease (AD) is the clinical manifestation of a neurodegenerative disorder characterized by pervasive and progressive cognitive decline with impairment in activities of daily living. According to the Centers for Disease Control the number of Americans with Alzheimer’s disease or dementia will grow to 13.9 million (2018 report) by 2060, making it an urgent public concern. Research in the last decade has focused on early identification of the disease and revealed a prodromal phase prior to the onset of functional impairments, known as mild cognitive impairment (MCI). Despite early identification, there are few treatment options to slow down progression from MCI to AD. Recent studies suggest that cognitive deficits 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. Specifically, neural synchrony in the gamma band (30-45Hz) plays a central role in top-down attention, multisensory processing, perceptual binding and working memory (WM) in healthy individuals. Gamma band responses (GBR) are impaired in individuals with AD spectrum disorders, and animal studies in AD models targeting GBR have shown positive effects on cognition. Thus, developing similar treatments targeting GBR are expected to improve cognition in individuals with MCI. Our group has administered EEG-neurofeedback (EEG-NFB) targeting GBR in SCZ patients, with promising early results (research strategy). NFB is a low-cost, safe, easily administered closed-loop neuromodulation technique where subjects are shown their brain activity as a visual metaphor and asked to modulate it in a given direction. EEG- NFB has been employed in multiple disorders ranging from ADHD, depression, to anxiety and in multiple populations including children and older adults. Based on these encouraging results, we are proposing a study to 1) test the efficacy of EEG-NFB targeting GBR in individuals with amnestic MCI compared to a sham/placebo, 2) explore the mechanism underlying change in cognition and 3) explore pre-treatment characteristics that predict treatment response.