The effects of stimulant medication on working memory functional connectivity in attention-deficit/hyperactivity disorder.
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.
Olin Neuropsychiatry Research Center, The Institute of Living/Hartford Hospital, Hartford, Connecticut 06106, USA.
Christina G
CG
Wong
Michael C
MC
Stevens
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects* / Q000503:physiopathology*; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D010296:Parietal Lobe / Q000187:drug effects* / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology
D000697:Central Nervous System Stimulants