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

项目概要 该项目旨在确定侵入性闭环电刺激如何可能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们——包括不断增长的患有神经退行性疾病的人群，例如 阿尔茨海默氏症——我们建议评估如何使用功能性大脑动力学来指导 直接大脑刺激的最佳时机、位置和特性。之前的工作有 确定了整个大脑神经活动的特定模式，主要是 theta (3-8 Hz) 和 gamma (30 Hz) 频段的频谱调制，可预测成功的记忆 编码和检索。我们最近观察到刺激对记忆的影响 编码取决于传递时的这些神经特征。此外， 我们已经证明了刺激的功能和结构连接概况 位点与刺激对记忆的有效性有关。在这里，我们的目的是阐明（1） 状态依赖性刺激是否可以单独用于调节编码和 检索过程，或者是否将通用刺激算法应用于两个阶段 可以更好地恢复功能，（2）当针对与内侧颞叶具有特定连接特征的区域时，刺激是否更有效，以及（3） 如何利用知识优化多个目标部位的同时刺激 这些站点的连接性。更广泛地说，该项目旨在确定是否 生物标记引导的闭环脑刺激可用于纠正病理性大脑 状态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.