Noninvasive Manipulation of Hippocampal-Cortical Brain Networks and Memory

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 DESCRIPTION (provided by applicant): Memory impairment occurs in a variety of neuropsychiatric conditions (e.g., depression and schizophrenia) and in many neurologic disorders (e.g., neurodegenerative disease and brain injury). Unfortunately, memory impairments have devastating consequences for life quality and there are no current treatments that reliably improve memory function. The goal of this project is to better understand a new procedure for the noninvasive enhancement of human hippocampal-cortical brain networks that are thought to critically support memory. This noninvasive brain-stimulation procedure can produce robust and lasting (at least ~24 hours) enhancement of hippocampal-cortical networks and concomitant improvement in long-term associative memory. However, relevant brain mechanisms must be more fully specified before this procedure can be more broadly applied to better understand and treat memory impairments. We therefore propose a collection of experiments that aim to answer three standing mechanistic questions. First, we aim to test whether distinct hippocampal-cortical brain networks can be selectively enhanced, which would determine whether stimulation acts on discrete targeted memory networks. Second, we aim to determine the timecourse and duration of these enhancements, which is essential for evaluation of putative neural mechanisms and of potential for clinical utility. Finally, we aim to test whethe the hippocampus is the key site of stimulation-induced enhancement of hippocampal-cortical networks by targeting intact versus surgically removed hippocampal tissue in individuals with unilateral medial temporalobectomy performed for treatment of refractory epilepsy. Impairments in stimulation-induced enhancement of hippocampal-cortical networks and memory when missing hippocampal tissue is targeted would confirm the necessary/causal role of hippocampus in the effects of stimulation. All proposed experiments involve sophisticated assessments of hippocampal-dependent memory function and of hippocampal-cortical brain networks. Findings will thus deeply inform understanding of stimulation effects while at the same time producing important information on the role of hippocampal-cortical networks in memory. Insights from this research could propel understanding of memory impairment and its treatment by noninvasive stimulation.