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Methylphenidate-mediated motor control network enhancement in patients with traumatic brain injury.

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Dorer, Charlie L 
Manktelow, Anne E 
Allanson, Judith 
Sahakian, Barbara J 
Pickard, John D 


PRIMARY OBJECTIVE: To investigate functional improvement late (>6 months) after traumatic brain injury (TBI). To this end, we conducted a double-blind, placebo-controlled experimental medicine study to test the hypothesis that a widely used cognitive enhancer would benefit patients with TBI. RESEARCH DESIGN: We focused on motor control function using a sequential finger opposition fMRI paradigm in both patients and age-matched controls. METHODS AND PROCEDURES: Patients' fMRI and DTI scans were obtained after randomised administration of methylphenidate or placebo. Controls were scanned without intervention. To assess differences in motor speed, we compared reaction times from the baseline condition of a sustained attention task. MAIN OUTCOMES AND RESULTS: Patients' reaction times correlated with wide-spread motor-related white matter abnormalities. Administration of methylphenidate resulted in faster reaction times in patients, which were not significantly different from those achieved by controls. This was also reflected in the fMRI findings in that patients on methylphenidate activated the left inferior frontal gyrus significantly more than when on placebo. Furthermore, stronger functional connections between pre-/post-central cortices and cerebellum were noted for patients on methylphenidate. CONCLUSIONS: Our findings suggest that residual functionality in patients with TBI may be enhanced by a single dose of methylphenidate.



Traumatic brain injury, functional MRI, functional connectivity, methylphenidate, structural connectivity, Adult, Brain Injuries, Traumatic, Brain Mapping, Case-Control Studies, Central Nervous System Stimulants, Cognition Disorders, Diffusion Magnetic Resonance Imaging, Female, Humans, Image Processing, Computer-Assisted, Linear Models, Magnetic Resonance Imaging, Male, Methylphenidate, Middle Aged, Motor Activity, Neural Pathways, Neuropsychological Tests, Oxygen, Reaction Time, Tomography, X-Ray Computed, White Matter, Young Adult

Journal Title

Brain Inj

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Informa UK Limited
Medical Research Council (G0001237)
Medical Research Council (G9439390)
Medical Research Council (G0600986)
Medical Research Council (G0600986/1)
The study was funded by the Evelyn Trust- grant number 06/20. C.D. was funded by the Clinical Academic Research Awards organized by the East of England Multi Professional Deanery. B.J.S. consults for Cambridge Cognition, Otsuka, Servier and Lundbeck. She holds a grant from Janssen/J&J and has share options in Cambridge Cognition. D.K.M. is supported by the Neuroscience Theme of the NIHR Cambridge Biomedical Research Centre and NIHR Senior Investigator awards, and by Framework Program 7 funding from the European Commission (TBIcare). He has received lecture and consultancy fees and support for research from Glaxo SmithKline, Solvay and Linde. E.A.S. is funded by the Stephen Erskine Fellowship, Queens' College, Cambridge, UK.