The effects of stimulant medication on working memory functional connectivity in
attention-deficit/hyperactivity disorder.
Author(s): Wong CG, Stevens MC.
Affiliation(s): Olin Neuropsychiatry Research Center, The Institute of Living/Hartford Hospital,
Hartford, Connecticut 06106, USA.
Publication date & source: 2012, Biol Psychiatry. , 71(5):458-66
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.
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