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

增强伽马带反应以改善轻度认知障碍患者的工作记忆

• 批准号: 10370329
• 负责人: Fiza Singh
• 金额: $ 67.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10370329
• 关键词: Accounting; Activities of Daily Living; Adult; Affect; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; American; Amyloid beta-42; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Animal Model; Animals; Anxiety; Area; Attention; Attention deficit hyperactivity disorder; Back; Base of the Brain; Binding; Biological Markers; Brain; Brain region; Butyric Acids; Centers for Disease Control and Prevention (U.S.); Characteristics; Child; Clinical; Cognition; Cognition Disorders; Cognitive deficits; Computers; Dementia; Disease; Disease Progression; Dose; Down Syndrome; Early identification; Effect Modifiers (Epidemiology); Elderly; Electroencephalography; Eye; Frequencies; Genetic; Genetic Risk; Histopathology; Impaired cognition; Impairment; Individual; Interneurons; Intervention; Mediating; Mediator of activation protein; Memory; Memory impairment; Mental Depression; Metaphor; Neocortex; Neurobiology; Neurodegenerative Disorders; Neurons; Neuropsychological Tests; Participant; Patients; Phase; Photic Stimulation; Placebos; Play; Population; Prediction of Response to Therapy; Prefrontal Cortex; Public Health; Randomized; Reading; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Senile Plaques; Short-Term Memory; Synaptic plasticity; Techniques; Testing; Training Programs; Visual; amnestic mild cognitive impairment; apolipoprotein E-4; base; cognitive load; cognitive reserve; cost; economic impact; efficacy testing; frontal lobe; functional disability; high risk; hippocampal pyramidal neuron; improved; indexing; mild cognitive impairment; multisensory; neural circuit; neural network; neurofeedback; neuromechanism; neuron loss; neuroregulation; novel; post intervention; prevent; primary outcome; recruit; relating to nervous system; response; risk variant; secondary outcome; tau Proteins; tau-1; therapy development; treatment response

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.

抽象的 阿尔茨海默病（AD）是一种神经退行性疾病的临床表现，其特征是 普遍且进行性的认知能力下降，并伴有日常生活活动受损。根据 疾病控制中心称，患有阿尔茨海默病或痴呆症的美国人人数将增至 13.9 人 到 2060 年将增加 100 万（2018 年报告），这使其成为公众迫切关注的问题。过去十年的研究主要集中在 早期识别疾病并揭示功能障碍发生前的前驱期， 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减缓 从 MCI 向下进展至 AD。最近的研究表明，认知缺陷可能是由异常的 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 和依赖于国家的方式。具体来说，伽玛波段（30-45Hz）的神经同步起着核心作用 健康人的自上而下注意力、多感觉处理、知觉结合和工作记忆（WM） 个人。患有 AD 谱系疾病的个体的伽马带反应 (GBR) 受损，而动物 针对 GBR 的 AD 模型研究显示对认知有积极影响。因此，开发类似的 针对 GBR 的治疗有望改善 MCI 患者的认知能力。我们组有 对 SCZ 患者进行针对 GBR 的脑电图神经反馈 (EEG-NFB)，取得了有希望的早期结果 （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，其中 受试者以视觉隐喻的形式展示他们的大脑活动，并要求其按照给定的方向进行调节。脑电图- NFB 已被用于治疗多种疾病，从多动症、抑郁症到焦虑症，以及多种疾病 人群包括儿童和老年人。基于这些令人鼓舞的结果，我们提出一项研究 1) 测试针对 GBR 的 EEG-NFB 在遗忘性 MCI 个体中的功效与 假手术/安慰剂，2）探索认知变化的机制，3）探索治疗前 预测治疗反应的特征。