Medial Septal Theta Frequency Stimulation Improves Spatial Working Memory Following Traumatic Brain Injury.

Darrin J. Lee, MD1, Gene Gurkoff, PhD1, Ali Izadi, BS1, Philip Schwartzkroin, PhD1, Robert Berman, PhD1, Jan Muizelaar, MD, PhD1, Bruce Lyeth, PhD1, Kiarash Shahlaie, MD, PhD1

1Sacramento, CA United States

Keywords: traumatic brain injury, memory, animal model, deep brain stimulation, electrical stimulation

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     Traumatic brain injury (TBI) often results in cognitive deficits, such as inattention and memory loss. Hippocampal theta oscillations are depressed following TBI and are important in learning and memory.
     In this study, we evaluate the effects of medial septal stimulation on spatial working memory following a lateral fluid percussion injury.
     48 male Sprague-Dawley rats (300-350g) underwent a sham (n=23) or moderate lateral fluid percussion injury (n=25).
     Immediately after injury, a medial septal stimulating electrode and hippocampal recording electrode ipsilateral to the injury were implanted. Beginning on post-procedure day 5, rats were tested with or without stimulation in a Barnes maze (spatial working memory task consisting of a circular platform with one escape hole, 17 non-escape holes, and four distinct visual cues) twice daily for three days. Rats were stimulated continuously at 80µA intensity, 7.7Hz frequency, and 1msec pulse width. Latency to finding the escape hole and number of errors were recorded.
     TBI animals without stimulation had longer latencies than sham animals (89.9±27.3 vs. 25.5±3.6 seconds, p<0.001). Stimulation significantly decreased average latency in TBI animals from 83.9±27.3 seconds to 25.8±4.8 seconds (p<0.001). Sham injured animals did not experience a significant change in latency with stimulation (p<0.05). There was no difference in number of errors across groups.
     This is a rat study.
     Medial septal stimulation in the theta frequency range results in improved spatial working memory following TBI in rats.
     Neuromodulation strategies, such as deep brain stimulation, warrant further investigation as novel treatments for improving outcome after TBI.


Project Roles:

D. Lee (), G. Gurkoff (), A. Izadi (), P. Schwartzkroin (), R. Berman (), J. Muizelaar (), B. Lyeth (), K. Shahlaie ()