Effect of methylphenidate on executive functioning in adults with attention-deficit/hyperactivity disorder: normalization of behavior but not related brain activity

Biol Psychiatry. 2004 Oct 15;56(8):597-606. doi: 10.1016/j.biopsych.2004.07.011.


Background: We examined the effect of prolonged methylphenidate (MPH) treatment on the functional neuroanatomy of executive functioning in adult men with attention-deficit/hyperactivity disorder (ADHD).

Methods: Positron emission tomography with [(15)O] water measured alterations of regional cerebral blood flow (rCBF) during the Paced Auditory Serial Addition Task and a control task in 10 ADHD and 11 normal control men. Attention-deficit/hyperactivity disorder men were imaged unmedicated and after a clinically optimal dose of MPH for 3 weeks.

Results: Methylphenidate improved ADHD task performance, reduced rCBF in the prefrontal cortex (PFC), and increased rCBF in the right thalamus and precentral gyrus. Comparisons between the ADHD and normal control groups showed that normal control participants exhibited greater anterior cingulate cortex and temporal gyrus rCBF than ADHD participants under both conditions. Executive functioning was associated with greater subcortical (basal ganglia and cerebellar vermis) activation in the ADHD than normal control group under both conditions.

Conclusions: Methylphenidate does not normalize task-related activity in ADHD. Task-related rCBF decreases in the PFC may be due to improved filtering out of task-irrelevant stimuli by way of MPH-mediated dopamine release in the PFC.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Attention Deficit and Disruptive Behavior Disorders / complications*
  • Attention Deficit and Disruptive Behavior Disorders / drug therapy
  • Behavioral Symptoms / drug therapy*
  • Behavioral Symptoms / etiology
  • Brain / anatomy & histology
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain Mapping
  • Case-Control Studies
  • Central Nervous System Stimulants / pharmacology*
  • Central Nervous System Stimulants / therapeutic use
  • Female
  • Humans
  • Male
  • Methylphenidate / pharmacology*
  • Methylphenidate / therapeutic use
  • Neuropsychological Tests
  • Positron-Emission Tomography / methods
  • Problem Solving / drug effects*
  • Regional Blood Flow
  • Task Performance and Analysis


  • Central Nervous System Stimulants
  • Methylphenidate