"Targeting memory-related neural oscillations with direct electrical stimulation"

Dr. Uma Mohan

NIH

Hosted by Peter Kaskan

More details: Memory loss affects an estimated 57 million people worldwide and represents a growing clinical and societal burden, yet effective treatments remain limited. Developing effective brain stimulation therapies requires understanding neural signals supporting distinct memory processes and how stimulation modulates these patterns. Direct electrical stimulation (DES) shows promise for treating neurological and psychiatric disorders, but the brain’s memory-related neural circuits and how they respond to stimulation remain poorly understood. To address this, I present multiscale investigations of neural oscillatory mechanisms underlying human memory and how they respond to stimulation using intracranial recordings and stimulation in neurosurgical epilepsy patients. First, I demonstrate that large-scale theta and alpha traveling waves propagate across the cortex in preferred directions that systematically differ between successful memory encoding and retrieval. This suggests wave direction coordinates distributed memory networks and identifies traveling waves as a translationally relevant stimulation target. Second, I describe how DES modulates three different memory-related neural patterns in parameter- and location-dependent manner. By systematically varying stimulation frequency, amplitude, and location, I show low-frequency stimulation predominantly inhibits neural activity while high-frequency stimulation excites. High-frequency cortical stimulation more reliably altered traveling wave direction, providing causal evidence that stimulation reshapes large-scale memory patterns. Additionally, low-amplitude, high-frequency stimulation of hippocampal locations increased memory-related high-frequency ripple oscillations. Finally, building on these studies, I present my future research plans aimed at restoring memory by targeting specific oscillatory patterns with stimulation. This includes open- and closed-loop stimulation to evoke and modulate high-frequency ripple oscillations and cortical traveling waves as patients perform distinct memory tasks. I will integrate dynamical systems model-based approaches to predict and optimize stimulation responses across spatial scales. Together, this work establishes a mechanistic framework for designing targeted neuromodulation therapies that leverage endogenous memory signals, with implications for treating memory disorders.