Gamma-Music Based Intervention for Mild Alzheimer's Disease

项目总结/摘要 阿尔茨海默氏病（AD）的特征在于认知缺陷，如记忆丧失，以及大脑中的缺陷。 驱动日常活动的动力。这些认知和动机缺陷与广泛的神经元 和突触萎缩，加上聚集的细胞外Aβ-斑块和tau蛋白沉积，以及非典型神经 多个频率的活动。最近在AD小鼠模型中的研究表明，诱导γ-淀粉样蛋白的表达， 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斑块和改善空间和识别记忆。在人类中，恢复伽马频率 活动，同时保持其相位-振幅耦合与θ带活动被证明恢复人类 老年人和轻度AD患者的记忆力表现，从而提供了一种有希望的途径， 一种新的治疗方法，可以防止脑萎缩，同时提高认知能力。尽管他们最近取得了成功，但这是一个 将伽马频率神经刺激从实验室研究转化为行为刺激的主要挑战 干预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;特别是， 可持续地提升情绪和奖励动机行为的干预措施，同时鼓励社会联系 可能是最有希望减缓AD的进展。听音乐涉及多个大脑网络 参与感觉处理、运动、语言、注意力、学习和记忆、情绪和奖励， 社会联系基于音乐的干预（MBIs）有可能控制症状，减缓疾病 进步，提高生活质量。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，我们提出了一个新的协议，以音乐为基础的大脑测试 刺激，gamma-MBI：自动适应基于音乐的干预的伽马光刺激。 利用听音乐是一种内在有益的活动这一事实，我们建议以音乐为载体 伽马射线感官刺激由于音乐包含theta波段的声能，音乐听是一种形式的theta- 带状无创脑刺激我们将测试和改进一种新的大脑刺激工具， 灯光加上自选的音乐，为轻度抑郁症患者提供基于伽马音乐的干预。 老年痴呆症结果将产生一个可靠地影响大脑活动的伽马刺激方案（Aim 1），是适应性的，激励和奖励使用（目标2），并将产生预测谁可能受益 γ-MBI（Aim 3）最多。通过弥合神经刺激和行为干预之间的差距 通过将音乐疗法与伽马波段神经刺激相结合，本项目旨在找到一种可持续的 干预延缓AD的进展。我们的团队是唯一有资格解决这一问题的所有方面 创新和雄心勃勃的项目。

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.