Gamma-Music Based Intervention for Mild Alzheimer's Disease

项目摘要/摘要 阿尔茨海默病(AD)的特征是认知缺陷，如记忆力丧失，以及 推动日常活动的动力。这些认知和动机缺陷与广泛分布的神经元有关。 和突触萎缩，伴随细胞外聚集的Aβ斑块和tau沉积，以及不典型神经 多个频率的活动。最近在阿尔茨海默病小鼠模型上的研究表明，诱导伽玛 具有非侵入性伽马频率(40赫兹)光闪烁和听觉音调刺激的振荡 减少Aβ斑块，改善空间和识别记忆。在人类身上，恢复伽马频率 在保持其与theta带活动的相位-幅度耦合的同时，人类活动被证明是恢复的 老年人和轻度阿尔茨海默病患者的记忆表现，因此提供了一条有希望的途径 可以在改善认知的同时预防脑萎缩的新疗法。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研究的主要挑战 干预。我们的目标是通过生活方式干预促进健康的神经认知老化；特别是， 可持续地提升情绪和奖励动机行为的干预措施，同时鼓励社会纽带 可能在减缓AD进展方面最有希望。音乐收听涉及多个大脑网络 参与感觉处理、运动、语言、注意力、学习和记忆、情绪和奖励，以及 社会联系。基于音乐的干预(MBIS)具有控制症状、延缓疾病的潜力 进步，提高生活质量。我们的实验室最近表明，为期八周的MBI可以提高听力 与奖励系统的功能连接。在这里，我们建议测试一种新的基于音乐的大脑协议 刺激，伽马-MBI：伽马光刺激，自动适应基于音乐的干预。 利用听音乐是一种本质上有益的活动这一事实，我们建议将音乐作为一种载体 用于伽马感官刺激。由于音乐包含theta频段的声能，所以听音乐是theta的一种形式。 带状无创脑刺激。我们将测试和改进一种使用伽马频率的新型脑刺激工具 灯光加上自己选择的音乐，为患有轻度疾病的参与者提供基于伽马音乐的干预 阿尔茨海默氏症。结果将产生可靠地影响大脑活动的伽马刺激方案(AIM 1)，是适应性的、激励的和有益的使用(目标2)，并将产生关于谁可能受益的预测 来自伽马-MBI的最多(目标3)。通过弥合神经刺激和行为干预之间的差距 通过将音乐疗法与伽马波段神经刺激相结合，本项目旨在找到一种可持续的 延缓AD进展的干预措施。我们的团队是唯一有资格解决这个问题的方方面面的人 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.