Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study.
BACKGROUND
Methylphenidate (MPH), the most widely prescribed psychostimulant to treat many neuropsychiatric conditions, is reported to improve attention and speed of processing in survivors of traumatic brain injury (TBI). The neural correlate of this efficacy, however, remains unclear.


OBJECTIVE
Using perfusion functional magnetic resonance imaging (fMRI) as a biomarker of regional neural activity, the current study aimed to examine the neural correlates of single-dose (0.3 mg/kg) MPH administration in a randomized double-blind placebo-controlled crossover study design.


METHODS
Twenty-three individuals with moderate to severe TBI were tested on two occasions approximately 1 week apart. Perfusion fMRI scanning was carried out at rest and while participants performed cognitive tasks requiring sustained attention and working memory.


RESULTS
Behaviorally, MPH significantly improved both accuracy and reaction time (RT) in the sustained attention task but only RT in the working memory task. A trend of global reduction of cerebral blood flow by MPH was observed in all task conditions including resting. Voxel-wise whole-brain analysis revealed an interaction effect of drug by condition (MPH-placebo X task-rest) for the sustained attention task in the left posterior superior parietal cortex and parieto-occipital junction (BA 7/19). The magnitude of drug-related deactivation of this area during task performance was correlated with improvement in RT.


CONCLUSIONS
Suppression of activity in this area during task performance may reflect a compensatory mechanism by which MPH ameliorates attention impairments in TBI.
Moss Rehabilitation Research Institute, Albert Einstein Healthcare Network, 50 Township Line Rd., Elkins Park, PA 19027, USA. kimj@einstein.edu
Junghoon
J
Kim
John
J
Whyte
Sunil
S
Patel
Eduardo
E
Europa
Jiongjiong
J
Wang
H Branch
HB
Coslett
John A
JA
Detre
D000328:Adult; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects; D008774:Methylphenidate / Q000494:pharmacology*; D008875:Middle Aged; D011930:Reaction Time / Q000187:drug effects; D017741:Survivors; D015599:Trauma Severity Indices; D055815:Young Adult
D000697:Central Nervous System Stimulants; D008774:Methylphenidate