Methylphenidate modulates sustained attention and cortical activation in survivors of traumatic brain injury: a perfusion fMRI study

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. 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. 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. 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. Suppression of activity in this area during task performance may reflect a compensatory mechanism by which MPH ameliorates attention impairments in TBI.