Gamma-Music Based Intervention for Mild Alzheimer's Disease

基于伽玛音乐的轻度阿尔茨海默病干预

• 批准号: 10703506
• 负责人: Edward W Large
• 金额: $ 52.69万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703506
• 关键词: Acoustics; Address; Adopted; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Amyloid beta-Protein; Atrophic; Attention; Auditory; Auditory area; Behavior Therapy; Behavioral; Brain; Cognition; Cognitive; Cognitive deficits; Complex; Coupled; Coupling; Deposition; Disease Progression; Elderly; Electroencephalography; Emotions; Frequencies; Functional Magnetic Resonance Imaging; Goals; Gold; Hippocampus; Human; Individual; Individual Differences; Intervention; Laboratory Study; Language; Learning; Light; Link; Memory; Memory Loss; Memory impairment; Methods; Moods; Motivation; Movement; Music; Music Therapy; Neurocognitive; Neurons; Participant; Patients; Performance; Periodicity; Phase; Photic Stimulation; Population; Protocols documentation; Qualifying; Quality of life; Rewards; Route; Senile Plaques; Sensory; Synapses; System; Technology; Testing; Time; Translating; United States National Institutes of Health; Visual; Work; behavior prediction; behavioral adherence; brain based; cerebral atrophy; cognitive function; comparison control; design; detector; efficacy evaluation; extracellular; improved; innovation; interest; intervention participants; lifestyle intervention; memory recognition; molecular marker; motivated behavior; mouse model; neural; neural circuit; neural model; neural network; noninvasive brain stimulation; novel; novel therapeutics; preservation; prevent; response; sensory cortex; social; social attachment; success; symptom management; tau Proteins; tool; visual stimulus

Project Summary / Abstract Alzheimer’s Disease (AD) is characterized by cognitive deficits such as memory loss, as well as deficits in the motivation that drives daily activities. These cognitive and motivational deficits are linked to widespread neuronal and synaptic atrophy, coupled with aggregated extracellular Aβ-plaque and tau deposits, and atypical neural activity across multiple frequencies. Recent work in mouse models of AD have shown that inducing gamma oscillations with a non-invasive gamma-frequency (40 Hz) light-flickering and auditory tone-stimulation regimes reduced Aβ plaques and improved spatial and recognition memory. In humans, restoring gamma-frequency activity while preserving its phase-amplitude coupling with theta-band activity are shown to recover human memory performance in older adults, and in patients with mild AD, thus offering a promising route towards a novel therapy that can prevent brain atrophy while improving cognition. Despite their recent successes, it is a major challenge to translate gamma-frequency neurostimulation from a laboratory study to a behavioral intervention. Our goal is to promote healthy neurocognitive aging using lifestyle interventions; in particular, interventions that sustainably elevate mood and reward motivated behavior while encouraging social bonding may be most promising in slowing the progression of AD. Music listening engages multiple brain networks involved in sensory processing, movement, language, attention, learning and memory, emotion and reward, and social connectedness. Music-Based Interventions (MBIs) have the potential to manage symptoms, slow disease progression, and improve quality of life. Our lab has recently shown that an eight-week MBI can increase auditory functional connectivity to the reward system. Here we propose to test a novel protocol for music-based brain stimulation, gamma-MBI: gamma-light stimulation that automatically adapts to music-based intervention. Harnessing the fact that music listening is an intrinsically rewarding activity, we propose to use music as a carrier for gamma sensory stimulation. As music contains theta-band acoustic energy, music listening is a form of theta- band noninvasive brain stimulation. We will test and refine a novel brain-stimulation tool using gamma-frequency lights coupled with self-selected music for a gamma-music-based intervention for participants with mild Alzheimer’s Disease. Results will yield a gamma-stimulation protocol that reliably influences brain activity (Aim 1), is adaptive, motivating and rewarding to use (Aim 2), and will generate predictions as to who might benefit the most from gamma-MBI (Aim 3). By bridging the gap between neurostimulation and behavioral intervention by combining music therapy with gamma-band neurostimulation, the present project aims to find a sustainable intervention that delays the progression of AD. Our team is uniquely qualified to address all aspects of this innovative and ambitious project.

项目摘要 /摘要 阿尔茨海默氏病（AD）的特征是认知缺陷，例如记忆力丧失，以及缺陷 驱动日常活动的动机。这些认知和动机缺陷与宽度神经元有关 和突触萎缩，与聚集的细胞外AβPlaquque和Tau沉积物结合，非典型中性 跨多个频率的活动。 AD小鼠模型的最新工作表明诱导伽玛 具有非侵入性伽马频率（40 Hz）轻巧和听觉音调刺激制度的振荡 减少了Aβ斑块，并改善了空间和识别记忆。在人类中，恢复伽马频率 活性在保留其相位振幅与theta波段活性的同时被证明可以恢复人类 老年人以及轻度AD患者的记忆力表现，因此为通往A 可以在改善认知的同时预防脑萎缩的新型疗法。尽管最近取得了成功，但这是 将γ频率神经刺激从实验室研究转化为行为的主要挑战 干涉。我们的目标是使用生活方式干预促进健康的神经认知衰老；尤其， 在鼓励社会联系的同时，可持续提高情绪和奖励动机行为的干预措施 在减慢AD的发展方面可能是最有希望的。音乐聆听与多个大脑网络参与 参与感官处理，运动，语言，注意力，学习和记忆，情感和回报，以及 社会联系。基于音乐的干预措施（MBI）有可能控制症状，疾病缓慢 进步并改善生活质量。我们的实验室最近表明，八周的MBI可以增加听觉 与奖励系统的功能连接。在这里，我们建议测试基于音乐的大脑的新颖协议 刺激，伽玛-MBI：自动适应基于音乐的干预措施的伽马光刺激。 利用音乐聆听是一种本质上有意义的活动的事实，我们建议将音乐用作载体 用于伽马感觉刺激。由于音乐包含theta频段的声学能量，音乐聆听是theta-的一种形式 条带无创脑刺激。我们将使用伽马频率测试和完善一种新型的脑刺激工具 灯光加上自选择的音乐，用于基于伽马音乐的干预措施 阿尔茨海默氏病。结果将产生可靠影响大脑活动的伽马刺激方案（目标 1），是适应性，动力和使用的奖励（AIM 2），并将产生关于谁可能受益的预测 最多来自伽玛 - MBI（AIM 3）。通过弥合神经刺激和行为干预之间的差距 通过将音乐疗法与γ波段神经刺激相结合，本项目旨在找到可持续的 延迟AD进展的干预措施。我们的团队具有独特的资格来解决此方面的各个方面 创新和雄心勃勃的项目。