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Single–dose methylphenidate induces shift in functional connectivity associated with positive longer term clinical response in adult attention–deficit/hyperactivity disorder

C. Pretzsch,V. Parlatini,Declan Murphy

Published 2025 in Scientific Reports

ABSTRACT

Stimulants, such as methylphenidate (MPH), are beneficial for attention-deficit/hyperactivity disorder (ADHD), but individual response varies. A deeper understanding of the mechanisms underpinning response is needed. Previous studies suggest that a single MPH dose modulates resting-state functional connectivity (rs-fc). We investigated whether single-dose induced rs-fc changes were associated with post-dose optimization clinical response. Fifty-six adults with ADHD underwent rs-functional magnetic resonance imaging (rs-fMRI) under placebo and a single MPH dose, before starting MPH treatment. Clinical response was measured at two months. We tested if a single MPH dose (vs. placebo) shifted rs-fc; how these shifts were associated with treatment response (categorical approach); and whether these associations were driven by improvement on either ADHD symptom domain. A single MPH dose (vs. placebo) increased rs-fc in three subcortical-cortical and cerebellar-cortical clusters. Enhanced rs-fc between the cerebellar vermis (lobule 6) and the left precentral gyrus was associated with a greater probability of responding to treatment (χ2(7) = 22.740, p = .002) and with an improvement on both inattentive and hyperactive/impulsive symptoms (both p ≤ .001). We provide proof-of-concept that the brain functional response to a single MPH dose, administered before starting routine treatment, is indicative of two-month clinical response in adult ADHD. This may encourage future replication using clinically applicable measures.

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