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

顶叶区域，包括后扣带皮层，参与了对回忆至关重要的大脑网络， 顺序记忆、自传体提取和情景模拟。区域的重要性，如 来自动物模型的数据强调了后扣带回到情景处理，非侵入性 成像研究，脑刺激实验和罕见的报告，使用直接记录的大脑活动， 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 以及这一区域如何与海马体记忆网络整合。 我们提出了三个高度创新的实验，以解决这些知识差距。首先，我们将获得 微电极记录从后扣带皮层在情节编码和检索。我们将 识别时间细胞，即提供时间上下文的直接表示的神经元群体 信息.我们还将确定情节边界细胞，这代表了一个互补的人口， 神经元对于情景构建至关重要。我们将识别MTL中的神经元组装， PCC中的涟漪活动。第二，我们将使用新的实验操作， 抗胆碱能药物东莨菪碱对执行情景记忆任务的人颅内EEG受试者的影响 同时记录海马和顶叶的活动（来自后扣带皮层）。基于我们 在该患者人群中使用这种操作的初步数据，我们预测我们将观察到 活动在2-5赫兹“慢θ”频率范围内，以及相称的变化， 在5-9 Hz“快θ”频带中的连通性。东莨菪碱的使用与 理解海马记忆回路中的胆碱能调制及其意义 退化性疾病如阿尔茨海默氏病会影响这些回路。最后，我们将使用直接大脑 在相同的实验受试者中，对后扣带皮层和角回施加刺激， 了解这些区域如何差异调节海马theta振荡，建立在我们的 使用这种实验方法发表的工作。这些实验将利用我们独特的 手术癫痫患者海马网络直接脑记录的机会。我们 在这一领域的专业知识，在我们公布的调查结果显示，从上一个资助期，支持我们的 收集这些拟议数据和生成新颖的高价值数据集的能力，这些数据集将使我们能够解决 上述知识差距。

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.