Our project aims to form a multi-site consortium that will carry out fundamental exper- iments to elucidate the mesoscopic and microscopic neural dynamics underlying human memory and use direct brain stimulation as a manipulative tool to study those dynamics. Additionally, we seek to create a dynamical timeseries model that predicts the evolution of brain activity during cognitive tasks and incorporates the e ects of stimulation-induced perturbations on the system. We will collect recording and stimulation data from 250 pa- tient volunteers as they perform carefully-matched verbal and spatial memory tasks. Dur- ing non-stimulation sessions, we will measure correlative neural biomarkers of memory encoding and retrieval using standard clinical depth electrodes and microwire recordings. To test the causal role of these biomarkers, we will employ direct brain stimulation to disrupt or upregulate neural activity, and measure ensuing changes in behavioral perfor- mance. With a set of causal biomarkers and predictive models in hand, we will ?nally ask whether model-driven stimulation paradigms o er us the ability to reliably modulate neural activity, and consequent behavior, in real-time.
Diseases of memory and cognition are among the most devastating for patients and families, but the complex neural circuity that gives rise to cognition poses a serious chal- lenge to e ective therapeutic interventions. Here we propose an ambitious, multi-site, collaborative e ort to uncover the meso- and microscale neural processes underlying di- verse forms of episodic memory, leveraging direct intracranial stimulation and dynamical modeling to de?nitively identify brain activity that is causally linked to successful cog- nition. In doing so, we will o er (1) insights and speci?c targets for future cognitive therapies, and (2) a framework for simulating the interaction between direct electrical stimulation and human neurophysiology.
