Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task Methylphenidate Normalizes Frontocingulate Underactivation During Error Processing in Attention-Deficit/Hyperactivity Disorder Methylphenidate Normalizes Resting-State Brain Dysfunction in Boys With Attention Deficit Hyperactivity Disorder Effects of methylphenidate on working memory functioning in children with attention deficit/hyperactivity disorder. Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder Methylphenidate and if-then plans are comparable in modulating the P300 and increasing response inhibition in children with ADHD Reward processing in male adults with childhood ADHD—a comparison between drug-naïve and methylphenidate-treated subjects Pattern Classification of Working Memory Networks Reveals Differential Effects of Methylphenidate, Atomoxetine, and Placebo in Healthy Volunteers Methylphenidate improves diminished error and feedback sensitivity in ADHD: An Evoked Heart Rate analysis The effect of methylphenidate on prefrontal cognitive functioning, inattention, and hyperactivity in velocardiofacial syndrome. Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder Misinterpreting Emotional Expressions in Attention-Deficit/Hyperactivity Disorder: Evidence for a Neural Marker and Stimulant Effects The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review. Clinical evaluation of subjective and objective changes in motor activity and attention in children with attention-deficit/hyperactivity disorder in a double-blind methylphenidate trial.
BACKGROUND Children with Attention Deficit Hyperactivity Disorder ( ADHD ) have deficits in motivation and attention that can be ameliorated with the indirect dopamine agonist Methylpheni date ( MPH ) . We used functional magnetic resonance imaging ( fMRI ) to investigate the effects of MPH in medication-naïve children with ADHD on the activation and functional connectivity of " cool " attentional as well as " hot " motivation networks . METHODS 13 medication-naïve children with ADHD were scanned twice , under either an acute clinical dose of MPH or Placebo , in a r and omised , double-blind design , while they performed a rewarded continuous performance task that measured vigilant selective attention and the effects of reward . Brain activation and functional connectivity was compared to that of 13 healthy age-matched controls to test for normalisation effects of MPH . RESULTS MPH normalised performance deficits that were observed in children with ADHD compared to controls . Under placebo , children with ADHD showed reduced activation and functional inter-connectivity in bilateral fronto-striato-parieto-cerebellar networks during the attention condition , but enhanced activation in the orbitofrontal and superior temporal cortices for reward . MPH within children with ADHD enhanced the activation of fronto-striato-cerebellar and parieto-temporal regions . Compared to controls , MPH normalised differences during vigilant attention in parieto-temporal activation and fronto-striatal and fronto-cerebellar connectivity ;  MPH also normalised the enhanced orbitofrontal activation in children with ADHD in response to reward . CONCLUSIONS MPH normalised attention differences between children with ADHD and controls by both up-regulation of dysfunctional fronto-striato-thalamo-cerebellar and parieto-temporal attention networks and down-regulation of hyper-sensitive orbitofrontal activation for reward processing . MPH thus shows context -dependent dissociative modulation of both motivational and attentional neuro-functional networks in children with ADHD Background Children with attention-deficit/hyperactivity disorder ( ADHD ) have deficits in performance monitoring often improved with the indirect catecholamine agonist methylpheni date ( MPH ) . We used functional magnetic resonance imaging to investigate the effects of single-dose MPH on activation of error processing brain areas in medication-naive boys with ADHD during a stop task that elicits 50 % error rates . Methods Twelve medication-naive boys with ADHD were scanned twice , under either a single clinical dose of MPH or placebo , in a r and omized , double-blind design while they performed an individually adjusted tracking stop task , design ed to elicit 50 % failures . Brain activation was compared within patients under either drug condition . To test for potential normalization effects of MPH , brain activation in ADHD patients under either drug condition was compared with that of 13 healthy age-matched boys . Results During failed inhibition , boys with ADHD under placebo relative to control subjects showed reduced brain activation in performance monitoring areas of dorsomedial and left ventrolateral prefrontal cortices , thalamus , cingulate , and parietal regions . MPH , relative to placebo , upregulated activation in these brain regions within patients and normalized all activation differences between patients and control subjects . During successful inhibition , MPH normalized reduced activation observed in patients under placebo compared with control subjects in parietotemporal and cerebellar regions . Conclusions MPH normalized brain dysfunction in medication-naive ADHD boys relative to control subjects in typical brain areas of performance monitoring , comprising left ventrolateral and dorsomedial frontal and parietal cortices . This could underlie the amelioration of MPH of attention and academic performance in ADHD We used resting-state functional magnetic resonance imaging ( RS-fMRI ) to investigate the acute effects of methylpheni date hydrochloride ( MPH ) on spontaneous brain activity in children with attention deficit hyperactivity disorder ( ADHD ) . In all , 23 boys with ADHD were scanned twice , under either 10 mg dose of MPH or placebo , in a r and omized , cross-over , counterbalanced placebo-controlled design . 32 Matched healthy controls were scanned once for comparison . Seven of the 23 ADHD boys participated in a follow-up 8-week MPH treatment . A regional homogeneity ( ReHo ) method was applied to characterize the local synchronization of spontaneous brain activity .  ADHD boys under placebo compared with controls showed decreased ReHo in bilateral dorsolateral prefrontal cortices and increased ReHo in bilateral sensorimotor and parieto-visual cortices . Relative to placebo , MPH upregulated ReHo in bilateral ventral prefrontal cortices and cerebellar vermis , and downregulated ReHo in right parietal and visual areas that overlapped with the abnormally enhanced activities . When under MPH , ReHo differences between patients and controls were no longer observed . The preliminary prediction analysis revealed that the decreased ReHo in right parietal cortex after the acute MPH was positively correlated with the decreased symptom scores after the 8-week MPH treatment in the seven patients . We show that an acute dose of MPH normalized all fronto-parieto-cerebellar dysfunctions in boys with ADHD during the resting state . Preliminary findings furthermore suggest the potential of RS-fMRI as a prognostic imaging tool to identify response to MPH treatment BACKGROUND AND AIMS Children with attention deficit/hyperactivity disorder ( ADHD ) often show deficits in working memory performance .  Methylpheni date ( MPH ) is an effective medication to improve these cognitive difficulties . This study aim ed to clarify which effect MPH induces on the underlying functional networks of working memory . METHODS Fourteen boys diagnosed with ADHD and 12 healthy controls were investigated using functional magnetic resonance imaging ( fMRI ) . Each patient was tested twice , once with medication and once without . The fMRI experiments consisted of three verbal N-back tasks with increasing difficulty . Functional images were acquired on a 3 Tesla head scanner . RESULTS On the behavioral level , medicated patients performed similar to healthy controls and significantly better than without medication . On the functional level , patients showed the expected frontal and parietal activations , which were more pronounced in the 2- and 3-back tasks . Healthy controls showed significantly more activation in these regions and additional activation in the cerebellum . Interestingly , patients showed an additional effect of laterality . Left-sided frontal and parietal activation in patients was significantly less pronounced than in controls . CONCLUSION Functional data indicate different activation patterns in verbal working memory tasks between healthy controls and patients with ADHD irrespective of medication condition . Intake of MPH led to a clear improvement on a behavioral level . However , this effect was not reflected by changes in functional brain organization . MPH-induced changes leading to better performance in verbal working memory tasks might be very subtle and therefore not detectable by fMRI Youth with attention deficit hyperactivity disorder ( ADHD ) have deficits in interference inhibition , which can be improved with the indirect catecholamine agonist methylpheni date ( MPH ) . Functional magnetic resonance imaging was used to investigate the effects of a single dose of MPH on brain activation during interference inhibition in medication-naïve ADHD boys . Medication-naïve boys with ADHD were scanned twice , in a r and omized , double-blind design , under either a single clinical dose of MPH or placebo , while performing a Simon task that measures interference inhibition and controls for the oddball effect of low-frequency appearance of incongruent trials . Brain activation was compared within patients under either drug condition . To test for potential normalization effects of MPH , brain activation in ADHD patients under either drug condition was compared with that of healthy age-matched comparison boys . During incongruent trials compared with congruent – oddball trials , boys with ADHD under placebo relative to controls showed reduced brain activation in typical areas of interference inhibition , including right inferior prefrontal cortex , left striatum and thalamus , mid-cingulate/supplementary motor area , and left superior temporal lobe . MPH relative to placebo  upregulated brain activation in right inferior prefrontal and premotor cortices . Under the MPH condition , patients relative to controls no longer showed the reduced activation in right inferior prefrontal and striato-thalamic regions . Effect size comparison , furthermore , showed that these normalization effects were significant . MPH significantly normalized the fronto-striatal underfunctioning in ADHD patients relative to controls during interference inhibition , but did not affect medial frontal or temporal dysfunction .  MPH therefore appears to have a region-specific upregulation effect on fronto-striatal activation A disturbed functioning of the prefrontal cortex , the anterior cingulate cortex , and an accordingly reduced P300 presumably underlies executive function deficits of children with attention deficit hyperactivity disorder ( ADHD ) . Using a combined classification and Go/NoGo task paradigm , the present study investigated whether medication with methylpheni date ( MPH ) modulates the P300 as measured by a high-density electroencephalogram ( EEG ) and facilitates response inhibition in children with ADHD . Further , effects of MPH were compared with effects of self-regulation by if-then plans ( Gollwitzer in Am Psychol 54 : 493–503 , 1999 ) . MPH as well as if-then plans modulated the P300 and improved inhibition of an unwanted response on a Go/NoGo task to the same level observed in children without ADHD . Importantly , self-regulation strategies might be a valuable alternative to medication with MPH in children with ADHD Rationale Dysfunctional reward processing has been proposed as a main deficit in attention-deficit/hyperactivity disorder ( ADHD ) , which could be modulated by treatment with methylpheni date ( MPH ) . Objectives We examined differences in reward processing in adulthood ( independent of actual ADHD ) depending on MPH treatment during childhood . Methods Eleven males with childhood ADHD treated with MPH , 12 drug-naïve males with childhood ADHD , and 12 controls matched by age , h and edness , and smoking behavior were studied drug-free using functional magnetic resonance imaging . BOLD-responses  were compared during a monetary incentive delay task using an ANOVA design focusing on the ventral striatum during anticipation and the orbitofrontal cortex during outcome . Results Controls , drug-naïve , and treated subjects did not differ significantly in their activations in the ventral striatum and orbitofrontal cortex . Explorative analyses revealed decreased insula activation during outcome of loss avoidance in drug-naïve subjects in comparison to both groups , while treated subjects did not differ from controls . Insula activation correlated significantly positive with harm avoidance in the treated group . Furthermore , comparing subjects with actual ADHD symptoms , remitters and controls we observed decreased putamen activition in ADHD persisters . Conclusions Basal ganglia reward processing seemed to be unrelated to MPH pretreatment , but was related to remission . On the other h and , the revealed differences between treated and drug-naïve subjects with childhood ADHD , i.e. , in the insula , give evidence for more pronounced abnormal activation in reward-associated brain regions in untreated subjects with childhood ADHD and underpin the need of prospect i ve studies on long-term effects of psychostimulant treatment Stimulant and non-stimulant drugs can reduce symptoms of attention deficit/hyperactivity disorder ( ADHD ) . The stimulant drug methylpheni date ( MPH ) and the non-stimulant drug atomoxetine ( ATX ) are both widely used for ADHD treatment , but their differential effects on human brain function remain unclear . We combined event-related fMRI with multivariate pattern recognition to characterize the effects of MPH and ATX in healthy volunteers performing a rewarded working memory ( WM ) task . The effects of MPH and ATX on WM were strongly dependent on their behavioral context . During non-rewarded trials , only MPH could be discriminated from placebo ( PLC ) , with MPH producing a similar activation pattern to reward . During rewarded trials both drugs produced the opposite effect to reward , that is , attenuating WM networks and enhancing task-related deactivations ( TRDs ) in regions consistent with the default mode network ( DMN ) . The drugs could be directly discriminated during the delay component of rewarded trials : MPH produced greater activity in WM networks and ATX produced greater activity in the DMN . Our data provide evidence that : ( 1 ) MPH and ATX have prominent effects during rewarded WM in task-activated and -deactivated networks ; ( 2 ) during the delay component of rewarded trials , MPH and ATX have opposing effects on activated and deactivated networks : MPH enhances TRDs more than ATX , whereas ATX attenuates WM networks more than MPH ; and ( 3 ) MPH  mimics reward during encoding . Thus , interactions between drug effects and motivational state are crucial in defining the effects of MPH and ATX Attention Deficit Hyperactivity Disorder ( ADHD ) is a developmental disorder that has previously been related to a decreased sensitivity to errors and feedback . Supplementary to the traditional performance measures , this study uses autonomic measures to study this decreased sensitivity in ADHD and the modulating effects of medication . Children with ADHD , on and off Methylpheni date ( Mph ) , and typically developing ( TD ) children performed a selective attention task with three feedback conditions : reward , punishment and no feedback .  Evoked Heart Rate ( EHR ) responses were computed for correct and error trials . All groups performed more efficiently with performance feedback than without . EHR analyses , however , showed that enhanced EHR decelerations on error trials seen in TD children , were absent in the medication-free ADHD group for all feedback conditions . The Mph-treated ADHD group showed ' normalised ' EHR decelerations to errors and error feedback , depending on the feedback condition . This study provides further evidence for a decreased physiological responsiveness to errors and error feedback in children with ADHD and for a modulating effect of Mph OBJECTIVE Methylpheni date ( MPH ) is commonly used to treat attention-deficit/hyperactivity disorder ( ADHD ) in all children , including those with velocardiofacial syndrome ( VCFS ) . Yet concerns have been raised regarding its safety and efficacy in VCFS . The goal of this study was to examine the safety and efficacy of MPH in children with VCFS . METHODS Thirty-four children and adolescents with VCFS and ADHD participated in a r and omized , controlled trial with a 2:1 ratio of MPH versus placebo . All subjects underwent a cardiological evaluation before and after MPH administration . The primary outcome measure was prefrontal cognitive performance following a single dose of MPH or placebo . A follow-up assessment was conducted after a 6-month treatment with MPH . RESULTS Compared with placebo , single MPH administration was associated with a more robust improvement in prefrontal cognitive performance , including achievements in the Hearts and Flowers executive function task and the visual continuous performance task . After 6 months of treatment , a 40 % reduction in severity of ADHD symptoms was reported by parents on the Revised Conners Rating Scale . All subjects treated with MPH reported at least one side effect , but it did not necessitate discontinuation of treatment . MPH induced an increase in heart rate and blood pressure that was usually minor , but was clinical ly significant in two cases . No differences in response to MPH were observed between catechol-O-methyltransferase Met versus Val carriers . CONCLUSION The use of MPH in children with VCFS appears to be effective and relatively safe . A comprehensive cardiovascular evaluation for children with VCFS before and during stimulant treatment is recommended Background Children with attention deficit hyperactivity disorder ( ADHD ) are characterised by developmentally inappropriate levels of hyperactivity , impulsivity and /or inattention and are particularly impaired when performing tasks that require a high level of cognitive control . Methylpheni date ( MPH ) and motivational incentives may help improve cognitive control by enhancing the ability to monitor response accuracy and regulate performance accordingly . Methods Twenty-eight children with DSM-IV ADHD ( combined type ) aged 9–15 years and pairwise-matched typically developing children ( CTRL ) performed a go/no-go task in which the incentives attached to performance on no-go trials were manipulated . The ADHD group performed the task off and on their usual dose of MPH . CTRL children performed the task twice but were never medicated . EEG data were recorded simultaneously and two electrophysiological indices of error monitoring , the error-related negativity ( ERN ) and error positivity ( Pe ) were measured . Amplitudes of each ERP were compared between diagnostic groups ( CTRL , ADHD ) , medication days ( Off MPH , On MPH ) and motivational conditions ( baseline – low incentive , reward , response cost ) . Results Error rates were lower in the reward and response cost conditions compared with baseline across diagnostic groups and medication days . ERN and Pe amplitudes were significantly reduced in ADHD compared with CTRL , and were significantly enhanced by MPH . Incentives significantly increased ERN and Pe amplitudes in the ADHD group but had no effect in CTRL . The effects of incentives did not interact with the effects of MPH on either ERP . Effect sizes were computed and revealed larger effects of MPH than incentives on ERN and Pe amplitudes . Conclusions The findings reveal independent effects of motivational incentives and MPH on two electrophysiological markers of error monitoring in children with ADHD , suggesting that each may be important tools for enhancing or restoring cognitive control in these children BACKGROUND In addition to cognitive impairment , there are disruptions to mood and emotion processing in attention-deficit/hyperactivity disorder ( ADHD ) but little is known about their neural basis . We examined ADHD disturbances in mood and emotion recognition and underlying neural systems before and after treatment with stimulant medication . METHODS Participants were 51 unmedicated ADHD adolescents and 51 matched healthy control subjects rated for depressed and anxious mood and accuracy for identifying facial expressions of basic emotion . Brain function was recorded using event-related potentials ( ERPs ) while subjects viewed these expressions . ADHD subjects were retested after 4 weeks , following treatment with methylpheni date ( MPH ) . RESULTS ADHD subjects showed a profile of emotion-related impairment : higher depression and anxiety , deficits in identifying threat-related emotional expressions in particular , and alterations in ERPs . There was a pronounced reduction in occipital activity during the early perceptual analysis of emotional expression ( within 120 msec ) , followed by an exaggeration of activity associated with structural encoding ( 120 - 220 msec ) and subsequent reduction and slowing of temporal brain activity subserving context processing ( 300 - 400 msec ) . Methylpheni date normalized neural activity and produced some improvement of emotion recognition but had no impact on negative mood . Improvements in neural activity with MPH were consistent predictors of improvement in clinical features of emotional lability and hyperactivity . CONCLUSIONS Objective behavioral and brain function measures of emotion processing may provide a valuable addition to the clinical armamentarium for assessing emotional disturbances in ADHD and the efficacy of stimulants for treating these disturbances BACKGROUND The effectiveness of psychostimulants , primarily methylpheni date ( MPH ) , in the treatment of Attention Deficit Hyperactivity Disorder ( ADHD ) in the general population of typically growing children and adolescents is well established through many R and omised Controlled Trials ( RCTs ) . AIMS AND METHODS We carried out a systematic review of all the RCTs in people with intellectual disabilities ( ID ) that assessed effectiveness of MPH on the core ADHD symptoms . OUTCOMES AND RESULTS We included 15 papers from 13 studies that were all on children and adolescents with ID ( 315 participants were on MPH and placebo respectively ) , 12 of which used a cross over design , and one used a parallel design . On average around 40 - 50 % responded to MPH in the ID group whereas around 70 - 80 % response rate is reported among the non-ID children . Because of the heterogeneity of the outcome data it was not possible to carry out a meta- analysis . Significant adverse events included sleep difficulties and poor appetite along with weight loss and also irritability , social withdrawal and increased motor activities including tic . CONCLUSIONS AND IMPLEMENTATION On the basis of the poor quality evidence that is available , it seems that MPH may be effective in some but not all children and adolescents with ID and ADHD The aim of this study was to determine drug-dependent effects on attention and motor activity in children with attention-deficit/hyperactivity disorder ( ADHD ) in a double-blind methylpheni date ( MPH ) trial using both subjective behavior ratings and objective measures of function . In particular , we were interested in the relationship between changes of those subjective and objective measures . A total of 44 ADHD children with the combined subtype completed a r and omized , double-blind , placebo-controlled , crossover trial with 2 doses of MPH ( 0.25 ; 0.5 mg/kg body weight ) and placebo . In each condition , computerized attention tasks were performed , teacher-behavior ratings were obtained , and actigraph data were collected in both clinical and naturalistic setting s. Trend tests revealed linear effects of MPH dose on actigraph data in the test session ( p = 0.02 ) and at school ( p = 0.001 ) , as well as on sustained attention ( p < 0.001 ) , while inhibitory control showed a quadratic dose-response curve ( p < 0.001 ) . Multivariate regression analyses revealed that changes of both , hyperactive-impulsive symptoms ( 28 % ) and inattentive symptoms ( 23 % ) could be explained by objective changes of motor activity . Thus , for clinical practice , it should be taken into account that behavior ratings of ADHD symptoms seemed to be predominantly influenced by changes of motor activity
RESULTS In ADHD patients the middle and inferior frontal gyri , basal ganglia , and cerebellum were most often affected by MPH .
The middle and inferior frontal gyri were frequently affected by MPH during inhibitory control tasks .
Throughout nine task-based fMRI studies investigating MPH 's effect on the brains of pediatric patients with ADHD , MPH result ed in increased activation within frontal lobes , basal ganglia , and cerebellum .
In most cases , this increase " normalized " activation of at least some brain areas to that seen in typically developing children
OBJECTIVE Attention-deficit/hyperactivity disorder ( ADHD ) is a psychiatric disorder affecting 5 % of children .
Methylpheni date ( MPH ) is a common medication for ADHD .
Studies examining MPH 's effect on pediatric ADHD patients ' brain function using functional magnetic resonance imaging ( fMRI ) have not been compiled .
The goals of this systematic review were to determine ( 1 ) which areas of the brain in pediatric ADHD patients are modulated by a single dose of MPH , ( 2 ) whether areas modulated by MPH differ by task type performed during fMRI data acquisition , and ( 3 ) whether changes in brain activation due to MPH relate to clinical improvements in ADHD-related symptoms .