Targeted closed-loop intracranial brain-stimulation to improve episodic memory

项目摘要 该项目旨在确定侵入性闭环电刺激如何潜在地挽救大脑中产生成功记忆的神经活动模式。 功能。着眼于帮助受记忆障碍影响的人-包括不断增长的患有神经退行性疾病的人口，例如 阿尔茨海默氏症-我们建议评估如何使用脑功能动力学来指导 直接脑刺激的最佳时机、位置和特性。之前的工作已经完成 确定了大脑中神经活动的特定模式，主要是预测成功记忆的theta(3-8赫兹)和伽马(30赫兹)频段的光谱调制 编码和检索。我们最近观察到刺激对记忆的影响 编码依赖于传送时的这些神经信号。此外， 我们已经证明了刺激的功能和结构连接性特征 SITE与刺激记忆的有效性有关。在此，我们旨在澄清(1) 状态依赖刺激是否可以单独用于调制编码和 检索过程，或者共同的刺激算法是否适用于这两个阶段 可以更优化地恢复功能，(2)当针对具有特定连接到内侧颞叶的区域时，刺激是否更有效，以及(3) 如何利用知识优化多个靶点的同时刺激 这些网站的连通性。更广泛地说，这个项目试图确定 生物标记物引导的闭环式脑刺激可用于矫正病理性脑 说明并恢复受损记忆系统的功能。

Project Summary This project aims to determine how invasive closed-loop electrical stimulation can potentially rescue patterns of neural activity in the brain that give rise to successful memory functions. With an eye towards helping people affected by disorders of memory – including the ever-growing population suffering from neurodegenerative diseases, such as Alzheimer's – we propose to assess how functional brain dynamics can be used to guide the optimal timing, location, and properties of direct brain stimulation. Prior work has identified specific patterns of neural activity across the brain, principally spectral modulations in the theta (3-8 Hz) and gamma (30+ Hz) bands, that predict successful memory encoding and retrieval. We recently observed that the effect of stimulation on memory encoding depends on these neural signatures at the time it is delivered. Furthermore, we have shown that the functional and structural connectivity profile of a stimulation site relates to the effectiveness of stimulation on memory. Here, we aim to elucidate (1) whether state-dependent stimulation can separately be used to modulate encoding and retrieval processes, or whether common stimulation algorithms applied to both phases can more optimally restore function, (2) whether stimulation is more effective when targeted to regions with specific connectivity profiles to the medial temporal lobe, and (3) how simultaneous stimulation at multiple target sites can be optimized with knowledge of the connectivities of those sites. More broadly, this project seeks to determine whether biomarker-guided, closed-loop brain stimulation can be used to correct pathologic brain states and restore the function of an impaired memory system.