Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury

• DOI: 10.1089/neu.2014.3744
• Publication Date: 2015-06-21T11:44:08Z
• Authors: 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
• Keywords: cognition; Male; hippocampal theta oscillation; Physical Injury - Accidents and Adverse Effects; Clinical Sciences; Electric Stimulation Therapy; Traumatic Brain Injury (TBI); Hippocampus; Rats, Sprague-Dawley; 03 medical and health sciences; 0302 clinical medicine; Behavioral and Social Science; Acquired Cognitive Impairment; 2.1 Biological and endogenous factors; Animals; Gamma Rhythm; Aetiology; Theta Rhythm; Maze Learning; Electrodes; Traumatic Head and Spine Injury; Neurology & Neurosurgery; traumatic brain injury; Rehabilitation; Neurosciences; Electroencephalography; deep brain stimulation; Brain Disorders; Electrodes, Implanted; Rats; Mental Health; medial septal nucleus; Brain Injuries; Neurological; Exploratory Behavior; Mental health; Septal Nuclei; Sprague-Dawley; Implanted; Cognition Disorders; Psychomotor Performance

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.