Intracranial EEG to test how noninvasive stimulation affects hippocampal-dependent memory - PROJECT SUMMARY/ABSTRACT The hippocampus plays a crucial role as part of a distributed brain network supporting memory for life events. This exploratory project seeks to develop an evidence base for the use of intracranial EEG (iEEG) to investigate how noninvasive stimulation can be used to modulate hippocampal network neural activity and thereby test its role in memory. Hippocampal Indirectly Targeted Stimulation (HITS) is a noninvasive stimulation approach that uses transcranial magnetic stimulation of parieto-occipital regions of the hippocampal network. Previous studies indicate that HITS can selectively alter hippocampal activity observed through fMRI and enhance memory performance. The critical challenge addressed by this exploratory project is understanding neural mechanisms for how HITS affects network activity and behavioral performance. iEEG offers superior temporal and spatial resolution, which will provide detailed information on how HITS affects memory-related neural activity. The research has three primary aims: (1) investigating the selectivity of HITS effects on iEEG activity of the hippocampal network, (2) testing whether HITS impacts the endogenous theta- rhythmic oscillatory activity of the hippocampal network, and (3) determining if HITS specifically modifies memory-related hippocampal iEEG activity. These aims are addressed through a series of experiments involving HITS and detailed behavioral testing in neurosurgical patients undergoing iEEG monitoring for clinical treatment of epilepsy. This exploratory research would establish the HITS-iEEG method and provide initial mechanistic insights, with experiments designed to provide information to motivate future research on how HITS could be used to address the specific hippocampal network abnormalities associated with memory impairments in different neurological and psychiatric disorders. Relevant to the goals of PA-21-219, the hippocampal network is disrupted in disorders that are of joint interest to NIMH and NINDS, including brain injury, epilepsy, Alzheimer’s disease, schizophrenia, major depression, and PTSD. Positive outcomes from this exploratory study would support future research on HITS applications to these disorders, including using detailed knowledge of HITS effects on hippocampal network neural activity to develop targeted interventions for the specific network abnormalities responsible for memory and cognitive impairments. Detailed knowledge of how HITS affects brain network function will also motivate scientific applications for the use of HITS as a tool to test theories of the brain-behavior relationships supporting memory for life events.
