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 .
Clinically Relevant Doses of Methylphenidate Significantly Occupy Norepinephrine Transporters in Humans In Vivo
BACKGROUND Attention-deficit/hyperactivity disorder is a psychiatric disorder that starts in childhood . The mechanism of action of methylpheni date , the most common treatment for attention deficit hyperactivity disorder , is unclear . In vitro , the affinity of methylpheni date for the norepinephrine transporter ( NET ) is higher than that for the dopamine transporter ( DAT ) . The goal of this study was to use positron emission tomography to measure the occupancy of brain norepinephrine transporter by methylpheni date in vivo in humans . METHODS We used (S , S)-[¹¹C ] methylreboxetine ( [¹¹C]MRB ) to determine the effective dose 50 ( ED₅₀ ) of methylpheni date for NET . In a within-subject design , healthy subjects ( n = 11 ) received oral , single-blind placebo and 2.5 , 10 , and 40 mg of methylpheni date 75 min before [¹¹C]MRB injection . Dynamic positron emission tomography imaging was performed for 2 hours with the High Resolution Research Tomograph . The multilinear reference tissue model with occipital cortex as the reference region was used to estimate binding potential non-displaceable ( BP(ND ) ) in the thalamus and other NET-rich regions . RESULTS BP(ND ) was reduced by methylpheni date in a dose-dependent manner in thalamus and other NET-rich regions . The global ED₅₀ was estimated to be .14 mg/kg ; therefore , the average clinical maintenance dose of methylpheni date ( .35-.55 mg/kg ) produces 70 % to 80 % occupancy of NET . CONCLUSIONS For the first time in humans , we demonstrate that oral methylpheni date significantly occupies NET at clinical ly relevant doses . The ED₅₀ is lower than that for DAT ( .25 mg/kg ) , suggesting the potential relevance of NET inhibition in the therapeutic effects of methylpheni date in attention-deficit/hyperactivity disorder
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 .