Selective effects of methylphenidate in attention deficit hyperactivity disorder: A functional magnetic resonance study

Vaidya, Chandan J.; Austin, Glenn; Kirkorian, Gary; Ridlehuber, Hugh W.; Desmond, John E.; Glover, Gary H.; Gabrieli, John D. E. · 1998 · OpenAlex-citations

DOI: 10.1073/pnas.95.24.14494

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Summary

This study investigates the neurobiological basis of Attention Deficit Hyperactivity Disorder (ADHD) by examining differences in frontal–striatal brain function and its modulation by methylphenidate (MPH) in children with ADHD compared to healthy controls. Motivated by evidence suggesting dopaminergic dysfunction in ADHD and the lack of direct evidence regarding how MPH affects brain activity in children, the researchers aimed to determine if frontal–striatal function differs between groups and if MPH modulates this function differently in ADHD versus healthy children. The study utilized functional magnetic resonance imaging (fMRI) to measure brain activation during response inhibition tasks. The participants included 10 male children diagnosed with ADHD and six healthy male controls, matched for age, grade, and IQ. Subjects performed two versions of a go/no-go task: a response-controlled version and a stimulus-controlled version. Each subject underwent two scanning sessions, one while off medication and one while on MPH (ADHD subjects took their prescribed dose; controls took 10 mg). fMRI data focused on the frontal lobes and striatal structures (caudate nucleus and putamen) to assess activation patterns during no-go trials, which require inhibitory control. Behavioral results showed that children with ADHD exhibited impaired inhibitory control, making more errors of commission than controls on both tasks. MPH improved response inhibition in both groups on the stimulus-controlled task, but only in the ADHD group on the response-controlled task. Neuroimaging revealed distinct group differences in baseline activation: ADHD children showed greater frontal activation on the response-controlled task and reduced striatal activation on the stimulus-controlled task compared to controls. Crucially, MPH modulated brain activation differently between groups on the stimulus-controlled task. While MPH increased frontal activation equally in both groups, it increased striatal activation in ADHD children but decreased it in healthy controls. No significant drug effects on striatal activation were observed on the response-controlled task. The findings suggest that ADHD is characterized by atypical frontal–striatal function, specifically involving underactivation of the striatum during certain inhibitory demands. The opposing effects of MPH on striatal activation in ADHD and healthy children indicate that the disorder involves atypical dopaminergic modulation. These results provide a potential biological marker for ADHD, supporting the hypothesis that the condition involves specific neurophysiological differences in brain regions responsible for inhibitory control. The study highlights that MPH’s therapeutic effects may stem from normalizing these atypical striatal responses, offering insights into the neurobiological mechanisms underlying ADHD and its treatment.

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• executive function