Medial septal nucleus theta frequency deep brain stimulation improves spatial working memory after traumatic brain injury.

More than 5,000,000 survivors of traumatic brain injury (TBI) live with persistent cognitive deficits, some of which likely derive from hippocampal dysfunction. Oscillatory activity in the hippocampus is critical for normal learning and memory functions, and can be modulated using deep brain stimulation techniques. In this pre-clinical study, we demonstrate that lateral fluid percussion TBI results in the attenuation of hippocampal theta oscillations in the first 6 days after injury, which correlate with deficits in the Barnes maze spatial working memory task. Theta band stimulation of the medial septal nucleus (MSN) results in a transient increase in hippocampal theta activity, and when delivered 1 min prior to training in the Barnes maze, it significantly improves spatial working memory. These results suggest that MSN theta stimulation may be an effective neuromodulatory technique for treatment of persistent learning and memory deficits after TBI.