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

摘要 阿尔茨海默病（AD）是一种神经退行性疾病的临床表现，其特征在于 广泛和进行性认知功能下降，日常生活活动受损。根据 美国疾病控制中心预计，美国阿尔茨海默病或痴呆症患者人数将增至13.9人。 到2060年将达到100万人（2018年报告），这使其成为公众迫切关注的问题。过去十年的研究集中在 疾病的早期识别并揭示了功能障碍发作之前的前驱期， 被称为轻度认知障碍（MCI）。尽管早期识别，但很少有治疗选择， 从MCI到AD的进展。最近的研究表明，认知缺陷可能源于异常的 分布式神经网络的同步 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 和国家依赖的方式。具体来说，伽马波段（30- 45 Hz）的神经同步起着核心作用 健康儿童在自上而下注意、多感觉加工、知觉联结和工作记忆中的作用 个体在患有AD谱系障碍的个体和动物中，γ带反应（GBR）受损。 针对GBR的AD模型的研究显示出对认知的积极作用。因此，开发类似 靶向GBR的治疗有望改善MCI患者的认知能力。我们集团 针对SCZ患者的GBR给予EEG神经反馈（EEG-NFB），具有有希望的早期结果 （研究战略）。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，并被要求将其调节到给定的方向。脑电图- NFB已被用于多种疾病，从ADHD，抑郁症，焦虑症和多种 包括儿童和老年人在内的人群。基于这些令人鼓舞的结果，我们提出了一项研究， 1）测试与对照组相比，EEG-NFB靶向GBR在患有遗忘型MCI的个体中的功效， 假手术/安慰剂，2）探索认知变化的潜在机制，3）探索治疗前 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.