title: Neurophysiological alterations during strategy-based verbal learning in traumatic brain injury.
abstract: BACKGROUND
  Verbal learning and strategic processing deficits are common sequelae of traumatic brain injury (TBI); however, the neurophysiological mechanisms underlying such deficits remain poorly understood.
  
  
  METHODS
  We performed functional magnetic resonance imaging (fMRI) in 25 individuals with chronic TBI (>1 year after injury) and 20 matched healthy controls. Subjects were scanned while encoding word lists, with free recall and recognition assessed after each scanning run. To vary the strategic processing load, participants learned semantically unrelated words (Unrelated condition), semantically related words under null instruction conditions (Spontaneous condition), and semantically related words following training on the use of a semantic clustering strategy (Directed condition).
  
  
  RESULTS
  Behavioral performance on recall, recognition, and semantic clustering improved significantly as follows: Unrelated < Spontaneous < Directed. Individuals with TBI exhibited impaired yet parallel behavioral performance relative to control participants. The fMRI measures of brain activity during verbal encoding revealed decreased activity in participants with TBI relative to controls in left dorsolateral prefrontal cortex (DLPFC; BA 9) and in a region spanning the left angular and supramarginal gyri (BA 39/40). Functional connectivity analysis revealed evidence of a functional-but not anatomical-breakdown in the connectivity between the DLPFC and other regions specifically when participants with TBI were directed to use the semantic encoding strategy.
  
  
  CONCLUSIONS
  After TBI, the DLPFC appears to be decoupled from other active brain regions specifically when strategic control is required. We hypothesize that approaches designed to help re-couple DLPFC under such conditions may aid TBI cognitive rehabilitation.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA. strang@nmr.mgh.harvard.edu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Strangman
authors.forename: Richard
authors.initials: R
authors.lastname: Goldstein
authors.forename: Therese M
authors.initials: TM
authors.lastname: O'Neil-Pirozzi
authors.forename: Kalika
authors.initials: K
authors.lastname: Kelkar
authors.forename: Christina
authors.initials: C
authors.lastname: Supelana
authors.forename: David
authors.initials: D
authors.lastname: Burke
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Katz
authors.forename: Scott L
authors.initials: SL
authors.lastname: Rauch
authors.forename: Cary R
authors.initials: CR
authors.lastname: Savage
authors.forename: Mel B
authors.initials: MB
authors.lastname: Glenn
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000328:Adult; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D006801:Humans; D007807:Language Tests; D007858:Learning / Q000502:physiology*; D007859:Learning Disabilities / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000033:anatomy & histology / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000033:anatomy & histology / Q000502:physiology; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology; D014705:Verbal Behavior / Q000502:physiology*