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: 10502921
• 负责人: Edward W Large
• 金额: $ 54.57万
• 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/10502921
• 关键词: Acoustic Stimulation; Acoustics; Address; Adopted; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Amyloid beta-Protein; Atrophic; Attention; Auditory; Auditory area; Base of the Brain; 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 (Brain); 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; Quality of life; Rewards; Route; Senile Plaques; Sensory; Synapses; System; Technology; Testing; Time; Translating; United States National Institutes of Health; Visual; Work; base; behavioral adherence; cerebral atrophy; cognitive function; design; detector; extracellular; improved; innovation; interest; intervention participants; lifestyle intervention; memory recognition; molecular marker; motivated behavior; mouse model; neural circuit; neural model; neural network; noninvasive brain stimulation; novel; novel therapeutics; preservation; prevent; relating to nervous system; 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.

项目概要/摘要 阿尔茨海默氏病 (AD) 的特点是认知缺陷，例如记忆丧失以及认知能力缺陷 这些认知和动机缺陷与广泛的神经元有关。 和突触萎缩，加上聚集的细胞外 Aβ 斑块和 tau 沉积物，以及非典型神经 最近在 AD 小鼠模型中的研究表明，诱导伽玛 具有非侵入性伽马频率 (40 Hz) 光闪烁和听觉音调刺激机制的振荡 减少 Aβ 斑块并改善人类的空间和识别记忆，恢复伽马频率。 活性，同时保持其与 θ 带活性的相位幅度耦合，被证明可以恢复人类 老年人和轻度 AD 患者的记忆表现，从而提供了一条有希望的途径 尽管最近取得了成功，但它仍然是一种可以预防脑萎缩并改善认知的新疗法。 将伽马频率神经刺激从实验室研究转化为行为研究的主要挑战 我们的目标是通过生活方式干预来促进健康的神经认知衰老； 持续提升情绪、奖励积极行为、同时鼓励社会联系的干预措施 听音乐可能最有希望减缓 AD 的进展，它会调动多个大脑网络。 涉及感觉处理、运动、语言、注意力、学习和记忆、情感和奖励，以及 基于音乐的干预措施（MBI）有可能控制症状、减缓疾病。 我们的实验室最近表明，为期八周的 MBI 可以提高听力。 在这里，我们建议测试一种基于音乐的大脑的新协议。 刺激，伽马-MBI：自动适应基于音乐的干预的伽马光刺激。 鉴于音乐聆听是一项本质上有益的活动，我们建议以音乐为载体 由于音乐含有 θ 波段声能，听音乐是 θ 波段的一种形式。 我们将使用伽马频率测试和改进一种新型脑刺激工具。 灯光与自选音乐相结合，为患有轻度症状的参与者提供基于伽玛音乐的干预 研究结果将产生一种能够可靠影响大脑活动的伽马刺激方案（Aim） 1)，具有适应性、激励性和使用回报性（目标 2），并将生成关于谁可能受益的预测 通过弥合神经刺激和行为干预之间的差距，发挥伽马-MBI 的最大作用（目标 3）。 通过将音乐疗法与伽马带神经刺激相结合，本项目旨在找到可持续的方法 我们的团队拥有独特的资格来解决该问题的各个方面。 创新且雄心勃勃的项目。