This exploratory project merges noninvasive brain stimulation with invasive/neurosurgical electrophysiological recordings in humans to identify mechanisms for how stimulation targeting the hippocampal network affects episodic memory performance. Hippocampal network dysfunction is associated with episodic memory impairments in a variety of neurologic and psychiatric disorders. Core regions of this network such as the hippocampus are too deep within the brain to be directly affected by well-validated noninvasive neuromodulation approaches. Hippocampal Indirectly Targeted Stimulation ("HITS") addresses this limitation by targeting the hippocampus indirectly via stimulation-accessible neocortical hippocampal-network locations, to which patterned transcranial magnetic stimulation is applied. HITS reliably improves episodic memory performance and increases fMRI activity of the hippocampal network, including the hippocampus. However, it is not clear how HITS affects neural activity to produce these effects. Memory performance is supported by spatiotemporally coordinated neural activity of the hippocampal network, such as in synchronization of thetafrequency band oscillatory activity. The investigators hypothesize that HITS directly influences this coordinated activity within the hippocampal network. Alternatively, HITS could have a variety of nonspecific, indirect, or neuromodulatory effects that are not necessarily specific to the hippocampal network. Intracranial EEG (iEEG) recorded from multi-contact depth macroelectrodes in patients undergoing neurosurgical procedures provides the required temporal and spatial precision needed to test the hypothesis that HITS directly impacts hippocampal network activity. The investigators therefore will perform HITS in patients undergoing iEEG. The investigators will determine the impact of HITS on activity of the hippocampal network versus on off-target brain areas. To test whether HITS influences the coordination of theta-band oscillatory activity that is especially important for memory, the investigators will use a stimulation rhythm that should maximally affect this activity (theta-burst patterned stimulation) versus control rhythms and will administer HITS during a memory task versus during task-free periods. This is an ideal exploratory project because HITS-iEEG has a strong scientific rationale but involves many technical and logistical challenges yet to be solved. Success could motivate highly impactful research using HITS-iEEG. For example, understanding neural mechanisms of how HITS improves episodic memory could illuminate how to achieve memory enhancement via other methods, such as by deep-brain stimulation, by portable noninvasive electrical stimulation methods, or by next-generation noninvasive stimulation technologies. This future research would have strong scientific potential, in providing stimulation-based causal tests of brain-behavior relationships for memory. Findings could motivate brain stimulation therapy for neurological and psychiatric memory disorders.
