title: Improved learning and memory with theta-burst stimulation of the fornix in rat model of traumatic brain injury.
abstract: OBJECTIVE
  Learning and memory deficits are a source of considerable morbidity after traumatic brain injury (TBI). We investigated the effect of different patterns of hippocampal stimulation via a fornix electrode on cognitively demanding tasks after TBI.
  
  
  METHODS
  Male Sprague-Dawley rats underwent fluid-percussion injury and were compared with sham-operated rats. Electrodes were implanted into the fornix and hippocampus, and stimulation of the fornix produced robust evoked potentials in the hippocampus. A 60-s delayed non-match-to-sample (DNMS) swim T-maze was serially performed using four stimulation patterns: no stimulation (No Stim), low-frequency stimulation (LFS, 5 Hz), high-frequency stimulation (HFS, 130 Hz), and theta-burst stimulation (TBS, 200 Hz in 50 ms trains, five trains per second; 60 µA biphasic pulses). In a separate cohort of sham and injured animals, Morris water maze (MWM) was performed with or without TBS.
  
  
  RESULTS
  In the DNMS swim T-maze, LFS and HFS did not significantly improve performance after TBI. However, there was a significant difference in performance between TBI + No Stim and TBI + TBS groups (P < 0.05) with no significant difference between Sham + No Stim and TBI + TBS. In the MWM, latency in the TBI + TBS group was significantly different from TBI + No Stim starting on day 2 (P < 0.05) and was not different from Sham + No Stim. The TBI + TBS group performed significantly more platform crossings in the probe trial (P < 0.01) and exhibited improved search strategy starting on day 3 (P < 0.05) compared with TBI + No Stim.
  
  
  CONCLUSIONS
  Deficits in learning and memory after TBI are improved with TBS of the hippocampus. HFS and LFS do not appear to produce as great an effect as TBS.
authors.affiliation: Department of Neurological Surgery, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Sweet
authors.forename: Katharine C
authors.initials: KC
authors.lastname: Eakin
authors.forename: Charles N
authors.initials: CN
authors.lastname: Munyon
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Miller
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology / Q000523:psychology / Q000628:therapy*; D004195:Disease Models, Animal; D004599:Electric Stimulation Therapy / Q000379:methods*; D020712:Fornix, Brain / Q000503:physiopathology*; D058542:Implantable Neurostimulators; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009483:Neuropsychological Tests; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013826:Theta Rhythm / Q000502:physiology*
keywords: brain stimulation; fornix; hippocampus; theta-burst stimulation; traumatic brain injury