Restoring Cognitive Function through Precision Neurostimulation: A Disease-Agnostic Approach Based on Convergent Hippocampal Dynamics.

PROJECT SUMMARY The hippocampus, a key part of our brain involved in memory and emotional regulation, often malfunctions in many brain disorders, from developmental issues like autism to neurodegenerative diseases such as Alzheimer’s Disease. This dysfunction can severely affect memory, social interactions, and overall quality of life. Traditional treatments usually target specific disease-related changes at the molecular or protein level but have had limited success. Our research aims to revolutionize this approach by focusing on the fundamental brain activity patterns of the hippocampus. We propose that by correcting these disrupted activity patterns, we can improve cognitive function regardless of the disorder’s cause. We will use six models of three common neurological disorders to define similar abnormalities in brain activity across disease groups and examine whether brain stimulation can improve both dynamics and performance in cognitive tests. We will extend this approach with in-silico experiments that will model an extensive range of pathophysiological processes and evaluate many more stimulation parameters than is currently feasible in biological models. Our iterative approach that combines in-vivo and in-silico approaches is poised to accelerate clinical translation of our studies. This new strategy could lead to groundbreaking treatments for a wide range of cognitive issues, potentially benefiting millions of people. By using advanced techniques to understand and address these brain activity disruptions, our work promises to pave the way for innovative therapies and better quality of life for those with cognitive impairments.