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，

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.