Direct Cortical Stimulation to Manipulate Human Memory Function (MEMSTIM)

直接皮层刺激操纵人类记忆功能 (MEMSTIM)

• 批准号: EP/X023060/1
• 负责人: Daniel Bush
• 金额: $ 215.21万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX023060%2F1
• 关键词: Direct; Cortical; Stimulation; Manipulate; Human

Our memories of past events define who we are and allow us to imagine and plan for the future. Gaining insight into the fundamental mechanisms of human memory function therefore has implications ranging from education, eye witness testimony, and the design of intelligent machines, to the treatment of memory dysfunction associated with stress, trauma, and dementia. Damage to the hippocampus can have profound effects on memory which, in severe cases, results in a complete inability to remember new events. Within the hippocampus, the activity of single 'place cells' and 'concept cells' code for specific locations, people, animals, and objects. It is believed that ongoing experience is rapidly captured by the strengthening of synaptic connections between these neurons before memory traces are 'consolidated' within a wider network of brain areas to support memory guided behaviour. Crucially, the neural mechanisms supporting these functions remain elusive. Electrophysiology data from rodents suggest that both consolidation and planning may be supported by the 'replay' of activity sequences in hippocampal neurons, but causal evidence from humans is missing. To bridge this explanatory gap, I will record hippocampal single cell activity in pre-surgical epilepsy patients performing cognitive tasks that probe the encoding, storage, and recall of event memories. In addition, I will use an innovative cortical stimulation paradigm to detect and disrupt memory for specific events in real time, looking for a causal role in memory guided behaviour; and state of the art MEG decoding techniques to extend these findings to the whole brain level. I will synthesise these results with existing knowledge from computational modelling, rodent electrophysiology and neuroimaging to provide direct empirical support for a neural level model of human memory function that links the dynamics of single cells in the human brain to behaviour, illuminating novel treatment pathways for memory disorders.

我们对过去事件的记忆决定了我们是谁，并允许我们想象和计划未来。因此，深入了解人类记忆功能的基本机制具有广泛的意义，从教育、目击证词、智能机器的设计，到与压力、创伤和痴呆相关的记忆功能障碍的治疗。海马体的损伤会对记忆产生深远的影响，在严重的情况下，会导致完全无法记住新事件。在海马体中，单个“位置细胞”和“概念细胞”的活动对特定的位置、人物、动物和物体进行编码。人们认为，在记忆痕迹在更广泛的大脑区域网络中“巩固”之前，这些神经元之间的突触连接的加强迅速捕获了正在进行的经验，以支持记忆引导的行为。关键是，支持这些功能的神经机制仍然难以捉摸。来自啮齿类动物的电生理学数据表明，海马神经元活动序列的“重播”可能支持巩固和规划，但缺乏来自人类的因果证据。为了弥补这一解释上的差距，我将记录术前癫痫患者执行认知任务时海马单细胞的活动，这些任务探测事件记忆的编码、存储和回忆。此外，我将使用一种创新的皮层刺激范式来实时检测和破坏特定事件的记忆，寻找记忆引导行为的因果作用；以及最先进的脑磁图解码技术，将这些发现扩展到整个大脑水平。我将把这些结果与来自计算建模、啮齿动物电生理学和神经影像学的现有知识综合起来，为人类记忆功能的神经水平模型提供直接的经验支持，该模型将人类大脑中单个细胞的动态与行为联系起来，为记忆障碍的新治疗途径提供启发。

项目成果

Wake slow waves in focal human epilepsy impact network activity and cognition.

• DOI: 10.1038/s41467-023-42971-3
• 发表时间: 2023-11-30
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Sheybani, Laurent;Vivekananda, Umesh;Rodionov, Roman;Diehl, Beate;Chowdhury, Fahmida A.;McEvoy, Andrew W.;Miserocchi, Anna;Bisby, James A.;Bush, Daniel;Burgess, Neil;Walker, Matthew C.
• 通讯作者: Walker, Matthew C.