Effects of short-term methylphenidate treatment on functional network connectivity in attention-deficit hyperactivity disorder

Motivation: Long-term treatment with methylphenidate for ADHD may not sustain initial treatment gains, potentially attributed to the development of tolerance over time. However, the underlying neural mechanisms remain unexplored. Goal(s): To investigate how methylphenidate treatment alters functional connectivity changes to an acute methylphenidate challenge within three resting-state networks implicated in ADHD dysfunction. Approach: Resting-state fMRI before and after the challenge was collected in children and adults with ADHD, at baseline and after 16-week treatment with methylphenidate or placebo. Results: Functional connectivity measures in the frontoparietal network in children became more similar to that of controls after 4-months of methylphenidate treatment. Impact: Methylphenidate has long-lasting effects on within-frontoparietal network connectivity, but lack of change in response to MPH-challenge after treatment suggests that there is no tolerance in this neurobiological parameter. Future investigations require long term follow-up to investigate neurobiological and symptom tolerance.