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Characterization of hippocampal subregional cross-frequency associations, and the effect of Deep Brain Stimulation on memory performance in Humans


Deep brain stimulation (DBS) of the Medial Temporal Lobe (MTL) in humans has offered promise for improving hippocampal-dependent learning and memory, yet little is known about how it modulates the electrophysiological mechanisms associated with hippocampal communication. Here, we explore the role of theta-gamma coupling, a putative entorhinal- hippocampal organizing mechanism, in successful memory formation, while human subjects implanted with intracranial electrodes engage in hippocampal-dependent memory tasks. Our results suggest that entorhinal area DBS, previously shown to be associated with memory enhancement, also results in substantial coupling of theta and gamma oscillations within the hippocampus, suggesting a possible mechanism for stimulation related memory enhancement. Further, we address hippocampal cross-frequency dynamics during encoding and retrieval at the level of hippocampal subfields, showing that CA1 theta high-gamma coupling increases preferentially during encoding of subsequently recollected objects, while both CA1 and CA2- 3-DG exhibit memory specific cross-frequency coupling changes during retrieval. Finally, we perform a multi-task analysis to assess how generalizable is the effect of DBS across multiple entorhinal stimulation targets, memory modalities, and stimulation protocols; our results show that stimulation of entorhinal white matter enhances declarative memory encoding.

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