RESULTS The fMRI analysis showed that methylpheni date significantly enhanced activation in bilateral inferior frontal cortex (IFC)/insula during inhibition and time discrimination but had no effect on working memory networks .
The meta- analysis , including 14 fMRI data sets and 212 children with ADHD , showed that stimulants most consistently enhanced right IFC/insula activation , which also remained for a subgroup analysis of methylpheni date effects alone .
A more lenient threshold also revealed increased putamen activation .
CONCLUSIONS Psychostimulants most consistently increase right IFC/insula activation , which are key areas of cognitive control and also the most replicated neurocognitive dysfunction in ADHD .
These neurocognitive effects may underlie their positive clinical effects
BACKGROUND Psychostimulant medication , most commonly the catecholamine agonist methylpheni date , is the most effective treatment for attention-deficit/hyperactivity disorder ( ADHD ) .
However , relatively little is known on the mechanisms of action .
Acute effects on brain function can eluci date underlying neurocognitive effects .
We tested methylpheni date effects relative to placebo in functional magnetic resonance imaging ( fMRI ) during three disorder-relevant tasks in medication-naïve ADHD adolescents .
In addition , we conducted a systematic review and meta- analysis of the fMRI findings of acute stimulant effects on ADHD brain function .
Developmental trajectories of brain volume abnormalities in children and adolescents with attention-deficit/hyperactivity disorder.
CONTEXT Various anatomic brain abnormalities have been reported for attention-deficit/hyperactivity disorder ( ADHD ) , with varying methods , small sample s , cross-sectional design s , and without accounting for stimulant drug exposure . OBJECTIVE To compare regional brain volumes at initial scan and their change over time in  medicated and previously unmedicated male and female patients with ADHD and healthy controls . DESIGN , SETTING , AND PARTICIPANTS Case-control study conducted from 1991 - 2001 at the National Institute of Mental Health , Bethesda , Md , of 152 children and adolescents with ADHD ( age range , 5 - 18 years ) and 139 age- and sex-matched controls ( age range , 4.5 - 19 years ) recruited from the local community , who contributed 544 anatomic magnetic resonance images . MAIN OUTCOME MEASURES Using completely automated methods , initial volumes and prospect i ve age-related changes of total cerebrum , cerebellum , gray and white matter for the 4 major lobes , and cau date nucleus of the brain were compared in patients and controls . RESULTS On initial scan , patients with ADHD had significantly smaller brain volumes in all regions , even after adjustment for significant covariates . This global difference was reflected in smaller total cerebral volumes ( -3.2 % , adjusted F(1,280 ) = 8.30 , P = .004 ) and in significantly smaller cerebellar volumes ( -3.5 % , adjusted F(1,280 ) = 12.29 , P = .001 ) . Compared with controls , previously unmedicated children with ADHD demonstrated significantly smaller total cerebral volumes ( overall F(2,288 ) = 6.65 ; all pairwise comparisons Bonferroni corrected , -5.8 % ; P = .002 ) and cerebellar volumes ( -6.2 % , F ( 2,288 ) = 8.97 , P<.001 ) . Unmedicated children with ADHD also exhibited strikingly smaller total white matter volumes ( F(2,288 ) = 11.65 ) compared with controls ( -10.7 % , P<.001 ) and with medicated children with ADHD ( -8.9 % , P<.001 ) . Volumetric abnormalities persisted with age in total and regional cerebral measures ( P = .002 ) and in the cerebellum ( P = .003 ) . Cau date nucleus volumes were initially abnormal for patients with ADHD ( P = .05 ) , but diagnostic differences disappeared as cau date volumes decreased for patients and controls during adolescence . Results were comparable for male and female patients on all measures . Frontal and temporal gray matter , cau date , and cerebellar volumes correlated significantly with parent- and clinician-rated severity measures within the ADHD sample ( Pearson coefficients between -0.16 and -0.26 ; all P values were < .05 ) . CONCLUSIONS Developmental trajectories for all structures , except cau date , remain roughly parallel for patients and controls during childhood and adolescence , suggesting that genetic and /or early environmental influences on brain development in ADHD are fixed , nonprogressive , and unrelated to stimulant treatment
RESULTS The fMRI analysis showed that methylpheni date significantly enhanced activation in bilateral inferior frontal cortex (IFC)/insula during inhibition and time discrimination but had no effect on working memory networks .
The meta- analysis , including 14 fMRI data sets and 212 children with ADHD , showed that stimulants most consistently enhanced right IFC/insula activation , which also remained for a subgroup analysis of methylpheni date effects alone .
A more lenient threshold also revealed increased putamen activation .
CONCLUSIONS Psychostimulants most consistently increase right IFC/insula activation , which are key areas of cognitive control and also the most replicated neurocognitive dysfunction in ADHD .
These neurocognitive effects may underlie their positive clinical effects
BACKGROUND Psychostimulant medication , most commonly the catecholamine agonist methylpheni date , is the most effective treatment for attention-deficit/hyperactivity disorder ( ADHD ) .
However , relatively little is known on the mechanisms of action .
Acute effects on brain function can eluci date underlying neurocognitive effects .
We tested methylpheni date effects relative to placebo in functional magnetic resonance imaging ( fMRI ) during three disorder-relevant tasks in medication-naïve ADHD adolescents .
In addition , we conducted a systematic review and meta- analysis of the fMRI findings of acute stimulant effects on ADHD brain function .