24Attention Deficit-Hyperactivity Disorder (ADHD) has been intensively studied in 25 neurodevelopmental research, with the aim to identify the neural substrates of the disorder. Prior 26 studies have established that brain oscillations in specific frequency ranges associated with attention 27 and motor tasks are altered in ADHD patients as compared to typically developing (TD) peers. We 28 hypothesized that the behavioral improvement following medication in ADHD patients should be 29 accompanied by a normalization in the modulation of such oscillations. We hence implemented a 30 double-blind placebo-controlled crossover design, where boys diagnosed with ADHD underwent 31 behavioral and MEG measurements during a spatial attention task while on and off stimulant 32 medication (methylphenidate, MPH). Results were compared with an age/IQ-matched TD group 33 performing the same task, to assess the effect of MPH on oscillatory activity in the alpha (7 -13Hz) 34and beta (15 -30Hz) bands. We observed that depression of beta band oscillation over motor cortex 35 in preparation to the response in ADHD boys on placebo were significantly lower as compared to the 36 TD group. Importantly MPH resulted in a normalization of the beta depression, which then reached 37 the same levels as in the control subjects. Furthermore, alpha power increased during the preparation 38 interval in the ADHD control group, supposedly reflecting working memory maintenance of the cue 39 information. This increase was significantly reduced in the ADHD group on MPH, reflecting a 40 reduced impact on working memory load. This is the first MEG study showing task related changes in 41 brain oscillations with MPH in children with ADHD. 42
Significance statement 43Brain oscillations in the alpha (7-13Hz) and beta (15-30Hz) frequency bands are thought to underly 44 different aspects of attentional processing and their aberrant modulation has been reported in ADHD. 45Here, we used a child-friendly adaptation of a Posner cueing paradigm to investigate such oscillations 46 in children with and without a diagnosis of ADHD, and further examined the effects of 47 methylphenidate (MPH) in the latter group. We showed that MPH restores aberrant patterns of beta 48 3 desynchronization and reduces alpha power during retention in the ADHD group, concomitant to an 49 improvement in behavioural performance. 50Attention-Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, 52 characterized by a pattern of inattentive and/or hyperactive and impulsive behavior associated with 53 impairments of functioning. 54Whereas behavioral therapies have often produced inconsistent results, pharmacological intervention 55 with stimulant medication is widely and effectively used as first line treatment (Faltinsen et al., 2019). 56The goal of this study was to investigate how the brain network dynamics reflecting the 57 pathophysiology of ADHD responds to administration of MPH in children with ADHD. In particular, 58 we sought to identify psychostimulants' effect...