Hippocampal Neural Correlates of Memory Enhancement Via Theta-Rhythmic Human Brain Stimulation Via Simultaneous TMS/fMRI

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PROJECT SUMMARY ABSTRACT Neural activity oscillating at theta-band frequencies (4-8-Hz) is thought to provide a temporal framework for episodic memory encoding within the hippocampus and to coordinate memory-related processing across a distributed hippocampal-cortical network (HCN). However, previous attempts to characterize the functional role of HCN theta-band activity in humans have been limited in their reliance on correlational neural activity recording methods that do not yield strong causal inferences. In previous research, my laboratory has demonstrated that theta-burst transcranial magnetic stimulation applied to cortical nodes of the HCN generates lasting changes in HCN memory function, relative to control stimulation. The overall goal of this proposed project is build on these previous findings by obtaining neural correlates of the impact of theta-burst stimulation on HCN memory processing. This will provide a causal test of the role of theta in human HCN memory processing. To accomplish this goal, we will use a novel method whereby network-targeted theta- burst stimulation is delivered concurrently with fMRI neuroimaging during performance of a memory task. We hypothesize that theta-burst stimulation delivered to a cortical node of the HCN will modulate hippocampal memory processing. The effects of this network-targeted theta-burst stimulation will be compared to two control conditions, one involving targeting a different network (network control) and one involving stimulation at a non-theta-burst frequency (frequency control). Furthermore, the memory task will allow us to distinguish effects of theta-burst stimulation on hippocampal-dependent memory processing versus on a control task that does not involve memory processing. We hypothesize that HCN-targeted theta-burst stimulation will cause greater hippocampal activity selectively during memory processing and will enhance memory formation relative to the various control conditions. This proposal offers training opportunities in sophisticated multi- method experimental designs and task-based fMRI analyses. Findings will inform theories of HCN memory processing. Furthermore, disrupted HCN theta oscillations have been implicated in memory disorders, and findings could therefore motivate new therapeutic applications of brain stimulation for memory impairments.