The effects of stimulant medication on working memory functional connectivity in attention-deficit/hyperactivity disorder

Biol Psychiatry. 2012 Mar 1;71(5):458-66. doi: 10.1016/j.biopsych.2011.11.011. Epub 2011 Dec 29.


Background: Working memory impairments are commonly found in attention-deficit/hyperactivity disorder (ADHD) and often improve with psychostimulant treatment. Little is known about how these medications affect the function of frontoparietal brain regions engaged for working memory. This study used functional magnetic resonance imaging (fMRI) to examine medication-related changes in brain activation and functional connectivity in ADHD.

Methods: Eighteen ADHD-combined subtype youths (ages 11-17) twice completed a Sternberg working memory fMRI task in a randomized, double-blind, placebo-controlled design. Medications were individualized as patients' standard, clinically effective psychostimulant (e.g., methylphenidate or dextroamphetamine/amphetamine combination) dose. Brain activity and functional connectivity were characterized using group independent component analysis. SPM5 repeated-measures t tests compared ADHD patients' network engagement and regional functional connectivity on and off medication.

Results: Independent component analysis identified six frontoparietal networks/components with hemodynamic responses to encoding/maintenance or retrieval phases of the Sternberg fMRI task. On medication, three of these networks significantly increased activation. Functional connectivity analyses found medication led to recruitment of additional brain regions that were not engaged into the networks when participants were on placebo. Also, medication strengthened connectivity of some frontoparietal regions. Many connectivity changes were directly related to improved working memory reaction time. Overall, there was strong evidence for regional functional connectivity changes following medication in structures previously implicated as abnormal in ADHD, such as anterior cingulate, ventrolateral prefrontal cortex, and precuneus.

Conclusions: Stimulant medication has widespread effects on the functional connectivity of frontoparietal brain networks, which might be a mechanism that underlies their beneficial effects on working memory performance.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / drug therapy
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Central Nervous System Stimulants / pharmacology*
  • Central Nervous System Stimulants / therapeutic use
  • Child
  • Double-Blind Method
  • Female
  • Frontal Lobe / drug effects*
  • Frontal Lobe / physiopathology*
  • Functional Neuroimaging / methods
  • Functional Neuroimaging / psychology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Imaging / psychology
  • Male
  • Memory, Short-Term / drug effects*
  • Memory, Short-Term / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Parietal Lobe / drug effects*
  • Parietal Lobe / physiopathology*
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology


  • Central Nervous System Stimulants