Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury

Darrin J. Lee, Gene G. Gurkoff, Ali Izadi, Stacey E. Seidl, Angela Echeverri, Mikhail Melnik, Robert F. Berman, Arne D. Ekstrom, J. Paul Muizelaar, Bruce G. Lyeth, Kiarash Shahlaie

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Traumatic brain injury (TBI) often results in persistent attention and memory deficits that are associated with hippocampal dysfunction. Although deep brain stimulation (DBS) is used to treat neurological disorders related to motor dysfunction, the effectiveness of stimulation to treat cognition remains largely unknown. In this study, adult male Harlan Sprague-Dawley rats underwent a lateral fluid percussion or sham injury followed by implantation of bipolar electrodes in the medial septal nucleus (MSN) and ipsilateral hippocampus. In the first week after injury, there was a significant decrease in hippocampal theta oscillations that correlated with decreased object exploration and impaired performance in the Barnes maze spatial learning task. Continuous 7.7 Hz theta stimulation of the medial septum significantly increased hippocampal theta oscillations, restored normal object exploration, and improved spatial learning in injured animals. There were no benefits with 100 Hz gamma stimulation, and stimulation of sham animals at either frequency did not enhance performance. We conclude, therefore, that there was a theta frequency-specific benefit of DBS that restored cognitive function in brain-injured rats. These data suggest that septal theta stimulation may be an effective and novel neuromodulatory therapy for treatment of persistent cognitive deficits following TBI.

Original languageEnglish (US)
Pages (from-to)1822-1832
Number of pages11
JournalJournal of Neurotrauma
Issue number22
StatePublished - Nov 15 2015
Externally publishedYes


  • cognition
  • deep brain stimulation
  • hippocampal theta oscillation
  • medial septal nucleus
  • traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology


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