title: Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury.
abstract: 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.
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.
authors.forename: Darrin J
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.
authors.forename: Gene G
authors.initials: GG
authors.lastname: Gurkoff
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.
authors.forename: Ali
authors.initials: A
authors.lastname: Izadi
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Seidl
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.
authors.forename: Angela
authors.initials: A
authors.lastname: Echeverri
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Melnik
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.|2 Center for Neuroscience, University of California , Davis, Sacramento, California.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Berman
authors.affiliation: 2 Center for Neuroscience, University of California , Davis, Sacramento, California.
authors.forename: Arne D
authors.initials: AD
authors.lastname: Ekstrom
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Muizelaar
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.|2 Center for Neuroscience, University of California , Davis, Sacramento, California.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Lyeth
authors.affiliation: 1 Department of Neurological Surgery, University of California , Davis, Sacramento, California.|2 Center for Neuroscience, University of California , Davis, Sacramento, California.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Shahlaie
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology* / Q000523:psychology*; D003072:Cognition Disorders / Q000209:etiology* / Q000523:psychology / Q000628:therapy*; D004599:Electric Stimulation Therapy; D004567:Electrodes, Implanted; D004569:Electroencephalography; D005106:Exploratory Behavior; D065818:Gamma Rhythm; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D018782:Maze Learning; D011597:Psychomotor Performance; D051381:Rats; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000503:physiopathology*; D013826:Theta Rhythm
keywords: cognition; deep brain stimulation; hippocampal theta oscillation; medial septal nucleus; traumatic brain injury