Executive Impairment Determines ADHD Medication Response: Implications for Academic Achievement Clinical symptoms and performance on the continuous performance test in children with attention deficit hyperactivity disorder between subtypes: a natural follow-up study for 6 months A context for normalizing impulsiveness at work for adults with attention deficit/hyperactivity disorder (combined type). Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate Neurocognitive performance and behavioral symptoms in patients with attention-deficit/hyperactivity disorder during twenty-four months of treatment with methylphenidate. Methylphenidate Normalizes Frontocingulate Underactivation During Error Processing in Attention-Deficit/Hyperactivity Disorder Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus. Childhood methylphenidate treatment of ADHD and response to affective stimuli Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHD. Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder 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. EEG phenotypes predict treatment outcome to stimulants in children with ADHD. Dissecting the attention deficit hyperactivity disorder (ADHD) phenotype: Sustained attention, response variability and spatial attentional asymmetries in relation to dopamine transporter (DAT1) genotype Adult outcome of attention-deficit/hyperactivity disorder: a controlled 16-year follow-up study. Impact of comorbid autism spectrum disorders on stimulant response in children with attention deficit hyperactivity disorder: a retrospective and prospective effectiveness study. Reward processing in male adults with childhood ADHD—a comparison between drug-naïve and methylphenidate-treated subjects
Methylpheni date ( MPH ) often ameliorates attention-deficit/hyperactivity disorder ( ADHD ) behavioral dysfunction according to indirect informant reports and rating scales . The st and ard of care behavioral MPH titration approach seldom includes direct neuropsychological or academic assessment data to determine treatment efficacy . Documenting “ cool ” executive-working memory ( EWM ) and “ hot ” self-regulation ( SR ) neuropsychological impairments could aid in differential diagnosis of ADHD subtypes and determining cognitive and academic MPH response . In this study , children aged 6 to 16 with ADHD inattentive type ( IT ; n = 19 ) and combined type ( n = 33)/hyperactive-impulsive type ( n = 4 ) ( CT ) participated in double-blind placebo-controlled MPH trials with baseline and r and omized placebo , low MPH dose , and high MPH dose conditions . EWM/ SR measures and behavior ratings/classroom observations were rank ordered separately across conditions , with nonparametric r and omization tests conducted to determine individual MPH response . Participants were subsequently grouped according to their level of cool EWM and hot SR circuit dysfunction . Robust cognitive and behavioral MPH response was achieved for children with significant baseline EWM/SR impairment , yet response was poor for those with adequate EWM/ SR baseline performance . Even for strong MPH responders , the best dose for neuropsychological functioning was typically lower than the best dose for behavior . Findings offer one possible explanation for why long-term academic MPH treatment gains in ADHD have not been realized . Implication s for academic achievement and medication titration practice s for children with behaviorally diagnosed ADHD will be discussed Background The aims of this study were to determine the time course of improvements in attention deficit hyperactivity disorder ( ADHD ) clinical symptoms and neurocognitive function in a realistic clinical setting , and the differences in ADHD symptom improvement using different classifications of ADHD subtypes . Methods The Child Behavior Checklist ( CBCL ) was completed by parents of ADHD children at the initial visit . The  computerized Continuous Performance Test ( CPT ) , Swanson , Nolan , and Pelham , and Version IV Scale for ADHD ( SNAP-IV ) , and  ADHD Rating Scale ( ADHD-RS ) were performed at baseline , one month , three months , and six months later , respectively . Patient care including drug therapy was performed at the discretion of the psychiatrist . The ADHD patients were divided into DSM-IV subtypes ( Inattentive , Hyperactive-impulsive and Combined type ) , and were additionally categorized into aggressive and non-aggressive subtypes by aggression scale in CBCL for comparisons . Results There were 50 ADHD patients with a mean age of 7.84 ± 1.64 years ; 15 of them were inattentive type , 11 were hyperactive-impulsive type , and 24 were combined type . In addition , 28 of the ADHD patients were grouped into aggressive and 22 into non-aggressive subtypes . There were significant improvements in clinical symptoms of hyperactivity and inattention , and impulsivity performance in CPT during the 6-month treatment . The clinical hyperactive symptoms were significantly different between ADHD patients sub-grouping both by DSM-IV and aggression . Non-aggressive patients had significantly greater changes in distraction and impulsivity performances in CPT from baseline to month 6 than aggressive patients . Conclusions We found that ADHD symptoms , which included impulsive performances in CPT and clinical inattention and hyperactivity dimensions , had improved significantly over 6 months under pragmatic treatments . The non-aggressive ADHD patients might have a higher potential for improving in CPT performance than aggressive ones . However , it warrant further investigation whether the different classifications of ADHD patients could be valid for predicting the improvements in ADHD patients ' clinical symptoms and neurocognitive performance Impaired executive function and impulsiveness or intolerance to boredom in adult attention deficit/hyperactivity disorder ( ADHD ) are thought to compromise performance at work . Several task parameters help people with ADHD to perform better on computerized cognitive tasks , namely reduced response-to-stimulus interval , discriminative feedback , or a format resembling a videogame . However , still very little is known about how these context s might be helpful in a real work environment . We developed a computerized task resembling a fast-paced videogame with no response-to-stimulus interval and constant and diverse discriminative error feedback . The task included several measurements of high-order executive function ( planning , working memory , and prospect i ve memory ) formatted as a single multitask simulating occupational activities ( SOA ) . We also administered the Continuous Performance Test-II ( CPT-II ) , a very simple vigilance task without discriminative feedback and with long response-to-stimulus intervals . We tested 30 adults answering to DSM-IV criteria of ADHD ( combined type ) and 30 IQ-matched adults without ADHD . As has been reported many times , the ADHD participants made significantly more errors of commission than the control participants on the CPT-II , whereas the two groups made the same number of errors of commission on the SOA . The ADHD group also sought discriminative feedback significantly more actively on the SOA than the control group and performed at par with the control group in all respects . There was no speed/accuracy trade-off , nor was there any evidence of other costs of normalization on the SOA . Impulsiveness in adult ADHD is compensable on a task simulating the work environment We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing , decreased tolerance to delays , poor temporal foresight and steeper temporal discounting . A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder ( ADHD ) . Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD . We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal , cingulate , striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds , motor timing to seconds and temporal discounting of longer time intervals . Given that impulsiveness , timing abnormalities and more specifically ADHD have been related to dopamine dysregulation , we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice , methylpheni date . This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor OBJECTIVE This study investigated the trends in neurocognitive function and behavioral symptoms among patients with attention-deficit/hyperactivity disorder ( ADHD ) during 24 months of treatment with methylpheni date in a clinical setting . METHODS Study participants consisted of 181 ADHD patients with a mean age of 13.4±2.5 years ( ages ranged from 8 to 18 years ; 151 boys and 30 girls ) who were prescribed oral short-acting methylpheni date two or three times daily , with each dose ranging between 0.3 and 1.0 mg/kg . At baseline and 6 , 12 , 18 , and 24 months from baseline , neurocognitive function was assessed using the  Test of Variables of Attention ( TOVA ) on the day the patient was off medication , and behavioral symptoms were evaluated using the Swanson , Nolan , and Pelham Version IV Scale for ADHD ( SNAP-IV ) parent form , the SNAP-IV teacher form , and the ADHD-Rating Scale ( completed by a child psychiatrist ) . RESULTS Of the 181 ADHD patients at the initial visit , 103 ( 56.9 % ) completed the study . During the 24-month methylpheni date treatment , only the commission errors in TOVA significantly improved ; however , the omission errors , response time , response time variability , response sensitivity , and ADHD score did not . The behavioral symptoms of ADHD , observed by various informants , all declined substantially , and were significantly correlated with each other during the long-term follow-up . The severity of teacher ratings was lower than that of parent and psychiatrist ratings . However , the teacher-rated inattention symptoms showed the strongest correlations with TOVA performance . CONCLUSIONS Findings suggest that neurocognitive deficits in ADHD patients , except inhibition ability , might be long lasting in realistic setting s. In addition , obtaining behavior profile assessment s from multiple informants , especially from teachers , is vital for establishing a complete underst and ing of ADHD patients 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 AIMS Type 2 diabetes mellitus ( DM ) develops when insulin resistance overcomes the capacity of compensatory insulin secretion . Insulin resistance may be induced via psychoneuroendocrine pathways , a possibility which has received little previous attention . METHODS We have used salivary cortisol measurements to monitor the activity of the hypothalamic-pituitary-adrenal ( HPA ) axis , the major controller of hormones involved in the regulation of peripheral insulin sensitivity under everyday conditions . The influence of external challenges , as well as the sensitivity of feedback regulation , were followed in r and omly selected middle-aged population sample s. RESULTS In health there is a rhythmicity of cortisol secretion , with a high plasticity and efficient feedback control . In contrast , a group of subjects were identified with a flat , rigid day curve and poor feedback control , who showed consistent abnormalities in stress-related cortisol secretion , including inhibited secretions of sex steroids and growth hormone ; insulin resistance ; abdominal obesity ; elevated leptin levels ; hyperglycaemia ; dyslipidaemia and hypertension with elevated heart rate . The endocrine abnormalities are probably responsible for the anthropometric and metabolic abnormalities . The circulatory perturbations seem to be induced by a parallel activation of the central sympathetic nervous system suggesting an ' hypothalamic arousal syndrome ' , gradually developing into an independent risk for disease . An associated cluster of environmental factors , including psychosocial and socio-economic stress , traits of depression and anxiety , alcohol consumption and smoking , all factors known to activate hypothalamic centres , has been identified . A polymorphism of the glucocorticoid receptor gene , with 13.7 % homozygotes in the male Swedish population , parallels receptor dysfunction , and may be responsible for the associated insulin resistance , central obesity and hypertension . CONCLUSIONS This is the first detailed examination of psychoneuroendocrinological processes in the natural environment on a population basis in relation to somatic health . The results suggest that an hypothalamic arousal syndrome , with parallel activation of the HPA axis and the central sympathetic nervous system , is responsible for development of endocrine abnormalities , insulin resistance , central obesity , dyslipidaemia and hypertension , leading to frank disease , including Type 2 DM . We suggest that this syndrome is probably based on environmental pressures in genetically susceptible individuals Neural correlates of emotional dysregulation in attention-deficit/hyperactivity disorder ( ADHD ) and persisting influence of Methylpheni date ( MPH ) still remain insufficiently understood . Decreased activation in the subgenual cingulate and the ventral striatum were found during the perception of positive and negative affective pictures in drug-naïve males with ADHD during childhood ( n=10 ) . Males with ADHD during childhood treated with MPH ( n=10 ) did not show any significant differences compared to healthy controls ( n=10 ) . Further prospect i ve studies need to clarify direct and indirect mechanisms of MPH treatment that may contribute to emotional processing , which is dysfunctional in males without pharmacological treatment in childhood There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder ( ADHD ) . In particular , it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development . Using computational neuroanatomic techniques , we estimated cortical thickness at > 40,000 cerebral points from 824 magnetic resonance scans acquired prospect ively on 223 children with ADHD and 223 typically developing controls . With this sample size , we could define the growth trajectory of each cortical point , delineating a phase of childhood increase followed by adolescent decrease in cortical thickness ( a quadratic growth model ) . From these trajectories , the age of attaining peak cortical thickness was derived and used as an index of cortical maturation . We found maturation to progress in a similar manner regionally in both children with and without ADHD , with primary sensory areas attaining peak cortical thickness before polymodal , high-order association areas . However , there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum : the median age by which 50 % of the cortical points attained peak thickness for this group was 10.5 years ( SE 0.01 ) , which was significantly later than the median age of 7.5 years ( SE 0.02 ) for typically developing controls ( log rank test χ(1)2 = 5,609 , P < 1.0 × 10−20 ) . The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning . Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported Attention-deficit hyperactivity disorder ( ADHD ) is a heritable disorder , prevalent from childhood through adulthood . Although the noradrenergic ( NA ) system is thought to mediate a portion of the pathophysiology of ADHD , genes in this pathway have not been investigated as frequently as those in the dopaminergic system . Previous association studies of one c and i date gene in the NA system , ADRA2A , showed inconsistent results with regard to an MspI polymorphism . In the current study , two nearby single-nucleotide polymorphisms , which define HhaI and DraI restriction fragment length polymorphisms , were also genotyped and were in significant linkage disequilibrium with the MspI RFLP . Transmission disequilibrium tests ( TDTs ) in a sample of 177 nuclear families showed significant association and linkage of the DraI polymorphism with the ADHD combined subtype ( P=0.03 ) , and the quantitative TDT showed association of this polymorphism with the inattentive ( P=0.003 ) and hyperactive-impulsive ( P=0.015 ) symptom dimensions . The haplotype that contained the less common allele of the DraI polymorphism likewise showed a strong relationship with the inattentive ( P=0.001 ) and hyperactive-impulsive ( P=0.004 ) symptom dimensions . This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism 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 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 This study demonstrates that the EEG phenotypes as described by Johnstone , Gunkelman & Lunt are identifiable EEG patterns with good inter-rater reliability . Furthermore , it was also demonstrated that these EEG phenotypes occurred in both ADHD subjects as well as healthy control subjects . The Frontal Slow and Slowed Alpha Peak Frequency and the Low Voltage EEG phenotype discriminated ADHD subjects best from controls ( however the difference was not significant ) . The Frontal Slow group responded to a stimulant with a clinical ly relevant decreased number of false negative errors on the CPT . The Frontal Slow and Slowed Alpha Peak Frequency phenotypes have different etiologies as evidence d by the treatment response to stimulants . In previous research Slowed Alpha Peak Frequency has most likely erroneously shown up as a frontal theta sub-group . This implies that future research employing EEG measures in ADHD should avoid using traditional frequency b and s , but dissociate Slowed Alpha Peak Frequency from frontal theta by taking the individual alpha peak frequency into account . Furthermore , the divergence from normal of the frequency b and s pertaining to the various phenotypes is greater in the clinical group than in the controls . Investigating EEG phenotypes provides a promising new way to approach EEG data , explaining much of the variance in EEGs and thereby potentially leading to more specific prospect i ve treatment outcomes ADHD is a childhood-onset behavioural disorder with a heterogeneous profile of neuropsychological impairment . Neuropsychological heterogeneity may , in part , reflect underlying genetic differences . Here we examined sustained attention , response variability and spatial attentional asymmetries in a sample of children and adolescents with ADHD ( n=22 ) in relation to dopamine transporter genotype ( DAT1 ) and also controls ( n=20 ) . Participants performed the sustained attention to response task ( SART ) ( testing sustained attention and response variability ) and the greyscales task ( a perceptual measure of attentional bias ) . The latter has previously been shown to yield a robust leftward attentional asymmetry in healthy subjects . The 10-repeat allele of the DAT1 gene has been associated with ADHD in a number of studies and appears to have biological significance . The ADHD group was sub-divided into those individuals with two copies of the " high-risk " 10-repeat allele ( high-risk DAT1 ) versus those with one or no copies of this allele ( low-risk DAT1 ) . The high-risk DAT1 ADHD group displayed greater response variability on the SART than either the low-risk DAT1 group or healthy controls , whereas the latter two groups did not differ . Further , the high-risk DAT1 group showed an attenuated spatial asymmetry , relative to the low-risk DAT1 ADHD group , who showed the typical leftward attentional asymmetry . Our results suggest that the 10-repeat DAT1 allele may mediate neuropsychological impairment in ADHD . The application of molecular genetics may help to define neuropsychological impaired subgroups of ADHD OBJECTIVE To estimate the risks for psychopathology and functional impairments in adulthood among a longitudinal sample of youth with and without attention-deficit/hyperactivity disorder ( ADHD ) diagnosed in childhood . METHOD This was a case-controlled , 16-year ( 15 - 19 years ) prospect i ve follow-up study of ADHD . 140 boys with and 120 without DSM-III-R ADHD were recruited from pediatric and psychiatric setting s. The main outcome measures were  structured diagnostic interviews and measures of psychosocial , educational , and neuropsychological functioning . Data were collected from 1988 to 2006 . RESULTS At the 16-year follow-up , subjects with ADHD continued to significantly differ from controls in lifetime rates of antisocial , mood , anxiety , and addictive disorders , but with the exception of a higher interval prevalence of anxiety disorders ( 20 % vs 8 % ; z = 2.32 , P = .02 ) and smoking dependence ( 27 % vs 11 % ; z = 2.30 , P = .02 ) , the incidence of individual disorders in the 6-year interval between the current and prior follow-up did not differ significantly from controls . At follow-up , the ADHD subjects compared with controls were significantly ( P < .05 ) more impaired in psychosocial , educational , and neuropsychological functioning , differences that could not be accounted for by other active psychopathology . CONCLUSIONS These long-term prospect i ve findings provide further evidence for the high morbidity associated with ADHD across the life cycle , stressing the importance of early recognition of this disorder for prevention and early intervention strategies . These findings also indicate that , in adulthood , ADHD confers significant risks for impairment that can not be accounted for by other psychopathology BACKGROUND In the recent past , psychiatrists and paediatricians have avoided prescribing stimulant medication , such as methylpheni date and dexamphetamine to patients with autism spectrum disorders ( ASD ) because of both doubts about efficacy and concern that these medications make stereotypies worse . Recently , a number of small trials have suggested that methypheni date does have a role in the management of hyperactivity in children with autistic spectrum disorders . METHODS Children with ASD and attention deficit hyperactivity disorder ( ADHD ) , and children with ADHD without ASD received st and ard treatment with methypheni date from one specialist centre . A combination of st and ardized and novel outcome tools was used to allow both an exploratory retrospective study of 174 children and then a prospect i ve study of a further 52 children to be carried out . RESULTS After treatment with stimulants , the subjects in both groups showed statistically significant improvements in target symptoms of ' hyperactivity ' , ' impulsivity ' , ' inattention ' , ' oppositionality ' , ' aggression ' and ' intermittent explosive rage ' . The Clinical Global Impression-Improvement and efficacy index measures also improved in each group . In both the retrospective and the prospect i ve studies , there was no statistically significant difference in the degree of improvements between each group . Importantly , neither tics nor repetitive behaviours worsened in either group . Children in the ' ADHD-only ' group who were prescribed stimulants experienced significant ' nausea ' , ' giddiness ' , ' headaches ' and ' sleep difficulties ' , whereas sleep difficulties were the only side effect that emerged in children in the ASD with ADHD group . CONCLUSIONS Both studies presented here support previous findings from smaller studies that show children with autism and ADHD can respond as well to stimulants as children with ADHD alone . Although r and omized controlled trials remain the gold st and ard for efficacy studies , systems like this that allow clinicians to continue rigorous and consistent monitoring for many years have a valuable role to play . Furthermore , such monitoring systems which now exist electronically can easily accumulate large data sets and reveal details about long-term effectiveness and long-term side effects of medication that are unlikely to be discovered in short-term trials 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
Our literature review identified ANS dysfunction in individuals with ADHD , more often in the direction of hypo-arousal than hyper-arousal , particularly at rest and during tasks requiring response regulation and sustained attention .
Stimulant medications  increased ANS activity and , in some studies , reinforcers and rewards produced a similar effect , suggesting that ANS function can be modified in ADHD .
Although arousal mechanisms have frequently been found to be atypical in ADHD , these findings usually emerged from indirect behavioural measures which give only a limited underst and ing of arousal dysregulation in this condition .