Journal Article

Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory

Cubillo, A., Barrett, N., Smith, A. B., Simmons, A., Brammer, M., Giampietro, V., Rubia, K.

2014

Overview

The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM). A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys. Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects. The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.

• Publisher: Cambridge University Press
• Subject: Adolescent / Analysis of Variance / Atomoxetine / Atomoxetine Hydrochloride / Attention Deficit Disorder with Hyperactivity - drug therapy / Attention Deficit Disorder with Hyperactivity - physiopathology / Attention deficit disorders. Hyperactivity / Attention deficit hyperactivity disorder / Basal Ganglia - drug effects / Basal Ganglia - physiopathology / Biological and medical sciences / Boys / Brain / Brain Mapping / Child / Child clinical studies / Compensation / Cortex / Cross-Over Studies / Dosage / Double-Blind Method / Drug therapy / Drugs / Frontal Lobe - drug effects / Frontal Lobe - physiopathology / Functional Laterality / Functional magnetic resonance imaging / Humans / Hyperactivity / Laterality / Lateralization / Magnetic Resonance Imaging - methods / Male / Males / Medical sciences / Memory / Memory, Short-Term - drug effects / Methylphenidate / Methylphenidate - administration & dosage / Methylphenidate - pharmacology / Methylphenidate - therapeutic use / Neuropharmacology / Neuropsychological Tests / Neurotransmitter Uptake Inhibitors - administration & dosage / Neurotransmitter Uptake Inhibitors - pharmacology / Neurotransmitter Uptake Inhibitors - therapeutic use / Normalization / Original Articles / Patients / Pharmacology. Drug treatments / Placebo effect / Placebos / Prefrontal Cortex - drug effects / Prefrontal Cortex - physiopathology / Propylamines - administration & dosage / Propylamines - pharmacology / Propylamines - therapeutic use / Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer / Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) / Psychology. Psychoanalysis. Psychiatry / Psychopathology. Psychiatry / Psychopharmacology / Short term memory / Treatment methods