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Problems with sustained attention are a key clinical feature of Attention Deficit/Hyperactivity Disorder (ADHD) which also manifests in poor performance and abnormal fronto-striato-parietal activation during sustained attention. Methylphenidate and atomoxetine improve attention functions and upregulate abnormal fronto-cortical activation during executive function tasks in ADHD patients. Despite this, no functional Magnetic Resonance Imaging (fMRI) study has compared the effects of methylphenidate and atomoxetine on the neurofunctional substrates of sustained attention in ADHD. This randomised, double-blind, placebo-controlled, cross-over study investigated the comparative normalisation effects of methylphenidate and atomoxetine on fMRI correlates and performance in 14 ADHD adolescents relative to 27 age-matched healthy controls during a parametric sustained attention/vigilance task with progressively increasing load of sustained attention. ADHD patients were scanned three times under a single clinical dose of either methylphenidate, atomoxetine, or placebo in pseudo-randomised order. Healthy controls were scanned once and compared to patients under each drug condition to test for potential drug-normalisation effects. Relative to controls, ADHD boys under placebo were impaired in performance and had underactivation in predominantly right-hemispheric fronto-parietal, and striato-thalamic regions. Both drugs normalised all underactivations, while only methylphenidate improved performance deficits. Within patients, methylphenidate had a drug-specific effect of upregulating left ventrolateral prefrontal/superior temporal activation relative to placebo and atomoxetine, while both drugs increased activation of right middle/superior temporal cortex, posterior cingulate, and precuneus relative to placebo. The study shows shared normalisation effects of methylphenidate and atomoxetine on fronto-striato-thalamo-parietal dysfunction in ADHD during sustained attention but a drug-specific upregulation effects of methylphenidate on ventral fronto-temporal regions., (Copyright © 2019. Published by Elsevier B.V.) more...

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato-thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto-striato-parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto-striato-cerebellar dysregulation in ASD. more...