Saturday, November 23, 2024
11/23/2024
PROJECT SUMMARY One of the most detrimental afflictions of the human condition is the inability to create or recall memories. As our population ages and the prevalence of neurodegenerative diseases increases, the burden of memory impairment is expected to surge. Hence, it is critical to develop novel interventions that improve memory performance. This project seeks to determine the mechanisms of human memory brain network activity and develop biomarker- guided, closed-loop electrical brain stimulation (EBS) that can be utilized to correct pathologic brain states and restore successful memory function. Specific patterns of neural activity across the brain, especially fluctuations in the theta (4-8Hz) and ripple (80-140Hz) frequencies, are correlated with successful human memory encoding and retrieval. We propose to further elucidate these brain dynamics and implement EBS guided by neurophysiology to improve memory function. The key innovations of this proposal are the application of direct, closed-loop EBS in awake humans that is precisely timed to endogenous memory network activity, and a focus on investigating and harnessing local electrophysiological rhythms in the theta and ripple frequencies for optimizing EBS. We will take advantage of our high-volume epilepsy surgical center specializing in stereoencephalography electrode implantation in neurosurgical patients. This represents a unique opportunity to record high-resolution, in-vivo electrophysiological recordings of human memory brain networks and apply EBS with high spatial and temporal precision. To succeed in this proposal, we will also draw upon our experience in utilizing open- and closed-loop EBS for the modulation of brain networks and our expertise in advanced analytic techniques. In Aim 1, we will elucidate the spatiotemporal properties of theta and ripple activity in memory encoding and recall that underlie successful episodic memory performance. In Aim 2, we will assess whether EBS for augmenting human memory function can be optimized by targeting endogenous theta memory network activity during memory encoding. This project is thoroughly integrated with a training plan that will provide the PI with a strong foundation for a successful physician-scientist career with a long-term goal of developing biomarker-based paradigms for neuromodulation modalities to optimize and expand treatment for neurological and neuropsychiatric applications.
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