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 .
Analysis of a large fMRI cohort: Statistical and methodological issues for group analyses
The aim of group fMRI studies is to relate contrasts of tasks or stimuli to regional brain activity increases . These studies typically involve 10 to 16 subjects . The average regional activity statistical significance is assessed using the subject to subject variability of the effect ( r and om effects analyses ) . Because of the relatively small number of subjects included , the sensitivity and reliability of these analyses is question able and hard to investigate . In this work , we use a very large number of subject ( more than 80 ) to investigate this issue . We take advantage of this large cohort to study the statistical properties of the inter-subject activity and focus on the notion of reproducibility by bootstrapping . We asked simple but important method ological questions : Is there , from the point of view of reliability , an optimal statistical threshold for activity maps ? How many subjects should be included in group studies ? What method should be preferred for inference ? Our results suggest that i ) optimal thresholds can indeed be found , and are rather lower than usual corrected for multiple comparison thresholds , ii ) 20 subjects or more should be included in functional neuroimaging studies in order to have sufficient reliability , iii ) non-parametric significance assessment should be preferred to parametric methods , iv ) cluster-level thresholding is more reliable than voxel-based thresholding , and v ) mixed effects tests are much more reliable than r and om effects tests . Moreover , our study shows that inter-subject variability plays a prominent role in the relatively low sensitivity and reliability of group studies
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 .