Neurophysiological alterations during strategy-based verbal learning in traumatic brain injury.
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.
Strangman
Gary E
GE
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA. strang@nmr.mgh.harvard.edu
Goldstein
Richard
R
O'Neil-Pirozzi
Therese M
TM
Kelkar
Kalika
K
Supelana
Christina
C
Burke
David
D
Katz
Douglas I
DI
Rauch
Scott L
SL
Savage
Cary R
CR
Glenn
Mel B
MB
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*