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 .
Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection
Inhibitory control and error detection are among the highest evolved human self-monitoring functions . Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success . Different brain regions in inferior , mesial , and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks . The widespread activation reflects the fact that the design s used so far have comeasured additional noninhibitory cognitive functions such as selective attention , response competition , decision making , target detection , and inhibition failure . Here we use rapid , mixed trial , event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions . The difficulty of the stop task , requiring withholding of a triggered motor response , was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials , failing on the other half . This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection . Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex . Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices , presumably reflecting an attention network for error detection
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 .