Using deep brain stimulation of the parietal cortex to investigate the electrophysiology of human episodic memory

顶叶区域，包括后扣带回皮质，参与了对记忆至关重要的大脑网络， 顺序记忆、自传体检索和情节模拟。区域的重要性，如 来自动物模型的非侵入性数据突出了发作过程的后扣带回 成像研究，脑刺激实验，以及使用直接记录的大脑活动的罕见报告 人类。然而，与特定的神经生理过程相关的重大知识差距仍然存在。 以及该区域如何与海马体记忆网络整合。 我们提出了三个极具创新性的实验来解决这些知识差距。首先，我们将获得 情景编码和提取过程中后扣带回的微电极记录。我们会 识别时间细胞，即提供时间上下文直接表示的神经元群体 信息。我们还将确定幕式边界细胞，它们代表了 对于间歇性结构至关重要的神经元。我们将确定MTL中的神经元组件及其伴随 PCC中的涟漪活动。其次，我们将使用新颖的实验性操作来管理 抗胆碱能药物东莨菪碱对执行情景记忆任务的人颅内脑电受试者的作用 并记录同时的海马区和顶叶活动(来自后扣带回皮质)。基于我们的 在这一患者群体中使用这种操作的初步数据，我们预测我们将观察到 2-5赫兹“慢波”频率范围内的活动，以及海马顶叶的相应变化 5-9赫兹“快速西塔”频段的连通性。东莨菪碱的使用与 理解海马体记忆回路中胆碱能调制及其对理解如何进行的启示 阿尔茨海默病等退行性疾病会影响这些回路。最后，我们将使用直接大脑 刺激相同实验对象的后扣带回和角回 了解这些区域如何以不同的方式调制海马theta振荡，基于我们的 使用这种实验方法出版的作品。这些实验将利用我们独特的 从外科癫痫患者的海马区网络中获得直接脑记录的机会。我们的 这一领域的专业知识，如我们在上一次资助期间公布的调查结果所显示的那样，支持我们的 能够收集这些建议的数据和生成性新颖、高价值的数据集，使我们能够解决 上面概述了知识差距。

Parietal regions, including the posterior cingulate cortex, participate in brain networks critical for recollection, order memory, autobiographical retrieval, and episodic simulation. The importance of regions such as the posterior cingulate to episodic processing has been highlighted by data from animal models, non—invasive imaging studies, brain stimulation experiments, and rare reports that use directly recorded brain activity in humans. However, significant knowledge gaps remain related to the specific neurophysiological processes that occur within the posterior cingulate and how this region integrates with hippocampal memory networks. We propose three highly innovative experiments to address these knowledge gaps. First, we will obtain microelectrode recordings from the posterior cingulate cortex during episodic encoding and retrieval. We will identify time cells, a population of neurons that provide direct representation of temporal contextual information. We will also identify episodic boundary cells, which represent a complementary population of neurons critical for episodic construction. We will identify neuronal assemblies in the MTL and concomitant ripple activity in the PCC. Second, we will use the novel experimental manipulation of administering the anticholinergic agent scopolamine to human intracranial EEG subjects performing an episodic memory task and record simultaneous hippocampal and parietal activity (from the posterior cingulate cortex). Based on our preliminary data using this manipulation in this patient population, we predict that we will observe a decrease in activity in the 2-5 Hz `slow theta’ frequency range, as well as commensurate changes in hippocampal—parietal connectivity in the 5-9 Hz `fast theta’ frequency band. The use of scopolamine has direct relevance for understanding cholinergic modulation in hippocampal memory circuits and implications for understanding how degenerative conditions such as Alzheimer’s Disease impact these circuits. Finally, we will use direct brain stimulation applied to the posterior cingulate cortex and angular gyrus in the same experimental subjects to understand how these regions may differentially modulate hippocampal theta oscillations, building on our published work using this experimental approach. These experiments will take advantage of our unique opportunity to obtain direct brain recordings from hippocampal networks in surgical epilepsy patients. Our expertise in this area, demonstrated in our published findings from the previous funded period, supports our ability to collect these proposed data and generative novel, high value datasets that will allow us to address the knowledge gaps outlined above.