Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task.
BACKGROUND
Children with Attention Deficit Hyperactivity Disorder (ADHD) have deficits in motivation and attention that can be ameliorated with the indirect dopamine agonist Methylphenidate (MPH). We used functional magnetic resonance imaging (fMRI) to investigate the effects of MPH in medication-naïve children with ADHD on the activation and functional connectivity of "cool" attentional as well as "hot" motivation networks.


METHODS
13 medication-naïve children with ADHD were scanned twice, under either an acute clinical dose of MPH or Placebo, in a randomised, double-blind design, while they performed a rewarded continuous performance task that measured vigilant selective attention and the effects of reward. Brain activation and functional connectivity was compared to that of 13 healthy age-matched controls to test for normalisation effects of MPH.


RESULTS
MPH normalised performance deficits that were observed in children with ADHD compared to controls. Under placebo, children with ADHD showed reduced activation and functional inter-connectivity in bilateral fronto-striato-parieto-cerebellar networks during the attention condition, but enhanced activation in the orbitofrontal and superior temporal cortices for reward. MPH within children with ADHD enhanced the activation of fronto-striato-cerebellar and parieto-temporal regions. Compared to controls, MPH normalised differences during vigilant attention in parieto-temporal activation and fronto-striatal and fronto-cerebellar connectivity; MPH also normalised the enhanced orbitofrontal activation in children with ADHD in response to reward.


CONCLUSIONS
MPH normalised attention differences between children with ADHD and controls by both up-regulation of dysfunctional fronto-striato-thalamo-cerebellar and parieto-temporal attention networks and down-regulation of hyper-sensitive orbitofrontal activation for reward processing. MPH thus shows context-dependent dissociative modulation of both motivational and attentional neuro-functional networks in children with ADHD.
Rubia
Katya
K
Department of Child Psychiatry, Institute of Psychiatry, King's College, London, UK. k.rubia@iop.kcl.ac.uk
Halari
Rozmin
R
Cubillo
Ana
A
Mohammad
Abdul-Majeed
AM
Brammer
Mick
M
Taylor
Eric
E
D000293:Adolescent; D001288:Attention / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology* / Q000627:therapeutic use; D009042:Motivation / Q000187:drug effects*; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000187:drug effects / Q000503:physiopathology; D012201:Reward
D000697:Central Nervous System Stimulants; D008774:Methylphenidate