Abstract

BackgroundWhile pharmacological treatment with Methylphenidate (MPH) is a first line intervention for ADHD, its mechanisms of action have yet to be elucidated. In a previous MEG study, we demonstrated that MPH in ADHD normalizes beta depression in preparation to motor responses (1). We here seek to identify the white matter tracts that mediate MPHs effect on beta oscillations. MethodsWe implemented a double-blind placebo-controlled crossover design, where boys diagnosed with ADHD underwent behavioral and MEG measurements during a spatial attention task while on and off MPH. Results were compared with an age/IQ-matched typically developing (TD) group performing the same task. Estimates of white matter tracts were obtained through diffusion tensor imaging (DTI). Based on aprioristic selection model criteria, we sought to determine the fiber tracts associated with electrophysiological, behavioral and clinical features of attentional functions. ResultsWe identified three main tracts: the anterior thalamic radiation (ATR), the Superior Longitudinal Fasciculus ( parietal endings) (SLFp) and Superior Longitudinal Fasciculus ( temporal endings) (SLFt). ADHD symptoms severity was associated with lower fractional anisotropy (FA) within the ATR. In addition, individuals with relatively higher FA in SLFp compared to SLFt showed faster and more accurate behavioral responses to MPH. Furthermore, the same parieto-temporal FA gradient explained the effects of MPH on beta modulation: subjects with ADHD exhibiting higher FA in SLFp compared to SLFt also displayed greater effects of MPH on beta power during response preparation. ConclusionsBased on MPHs modulatory effects on striatal dopamine levels, our data suggest that the behavioral deficits and aberrant oscillatory modulations observed in ADHD depend on a structural connectivity imbalance within the SLF, caused by a diffusivity gradient in favor of temporal rather than parietal, fiber tracts.