Neural Correlates of the Propensity for Retaliatory Behavior in Youths With Disruptive Behavior Disorders. Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate Impact of treatments for depression on comorbid anxiety, attentional, and behavioral symptoms in adolescents with selective serotonin reuptake inhibitor-resistant depression. Methylphenidate Normalizes Fronto-Striatal Underactivation During Interference Inhibition in Medication-Naïve Boys with Attention-Deficit Hyperactivity Disorder Brain gray matter deficits at 33-year follow-up in adults with attention-deficit/hyperactivity disorder established in childhood. Risperidone effects in the presence/absence of psychostimulant medicine in children with ADHD, other disruptive behavior disorders, and subaverage IQ. Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task The effects of methylphenidate on neural systems of attention in attention deficit hyperactivity disorder. 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 Atomoxetine Improved Response Inhibition in Adults with Attention Deficit/Hyperactivity Disorder Effect of vitamin D treatment in children with attention-deficit hyperactivity disorder Common and unique therapeutic mechanisms of stimulant and nonstimulant treatments for attention-deficit/hyperactivity disorder. Slow oscillating transcranial direct current stimulation during non-rapid eye movement sleep improves behavioral inhibition in attention-deficit/hyperactivity disorder Methylphenidate and if-then plans are comparable in modulating the P300 and increasing response inhibition in children with ADHD Childhood methylphenidate treatment of ADHD and response to affective stimuli 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 Co-morbid disruptive behavior disorder and aggression predict functional outcomes and differential response to risperidone versus divalproex in pharmacotherapy for pediatric bipolar disorder. Long-acting methylphenidate has an effect on aggressive behavior in children with attention-deficit/hyperactivity disorder. Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder Shared and Drug-Specific Effects of Atomoxetine and Methylphenidate on Inhibitory Brain Dysfunction in Medication-Naive ADHD Boys Misinterpreting Emotional Expressions in Attention-Deficit/Hyperactivity Disorder: Evidence for a Neural Marker and Stimulant Effects A Randomized Controlled Trial Investigating the Effects of Neurofeedback, Methylphenidate, and Physical Activity on Event-Related Potentials in Children with Attention-Deficit/Hyperactivity Disorder.
OBJECTIVE Youths with disruptive behavior disorders ( DBD ) ( conduct disorder and oppositional defiant disorder ) have an elevated risk for maladaptive reactive aggression . Theory suggests that this is due to an elevated sensitivity of basic threat circuitry implicated in retaliation ( amygdala/periaqueductal gray ) in youths with DBD and low levels of callous-unemotional traits and dysfunctional regulatory activity in the ventromedial prefrontal cortex in youths with DBD irrespective of callous-unemotional traits . METHOD A total of 56 youths 10 - 18 years of age ( 23 of them female ) participated in the study : 30 youths with DBD , divided by median split into groups with high and low levels of callous-unemotional traits , and 26 healthy youths . All participants completed an ultimatum game task during functional MRI . RESULTS Relative to the other groups , youths with DBD and low levels of callous-unemotional traits showed greater increases in activation of basic threat circuitry when punishing others and dysfunctional down-regulation of the ventromedial prefrontal cortex during retaliation . Relative to healthy youths , all youths with DBD showed reduced amygdala-ventromedial prefrontal cortex connectivity during high provocation . Ventromedial prefrontal cortex responsiveness and ventromedial prefrontal cortex-amygdala connectivity were related to patients ' retaliatory propensity ( behavioral responses during the task ) and parent-reported reactive aggression . CONCLUSIONS These data suggest differences in the underlying neurobiology of maladaptive reactive aggression in youths with DBD who have relatively low levels of callous-unemotional traits . Youths with DBD and low callous-unemotional traits alone showed significantly greater threat responses during retaliation relative to comparison subjects . These data also suggest that ventromedial prefrontal cortex-amygdala connectivity is critical for regulating retaliation/reactive aggression and , when dysfunctional , contributes to reactive aggression , independent of level of callous-unemotional traits 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 To assess the relative efficacy of antidepressant medication , alone and in combination with cognitive behavioral therapy ( CBT ) , on comorbid symptoms of anxiety , attention , and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents ( TORDIA ) trial . METHOD Adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression ( N = 334 ) were r and omly assigned to a medication switch alone ( to another SSRI or to venlafaxine ) or to a medication switch plus CBT .  Anxiety , attention-deficit/hyperactivity disorder ( ADHD ) , and disruptive behavior disorder ( DBD ) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks . The differential effects of medication and of CBT , and the impact of remission on the course of comorbid symptoms and diagnoses , were assessed using generalized linear mixed models . RESULTS Remission was associated with a greater reduction in scalar measures of anxiety , ADHD , and DBDs , and a greater decrease in the rate of diagnosed anxiety disorders . The correlations between the changes in symptoms of depression on the CDRS-R and anxiety , ADHD , and oppositional symptoms were modest , ranging from r = 0.12 to r = 0.28 . There were no significant differential treatment effects on diagnoses , or corresponding symptoms . CONCLUSION The achievement of remission had a beneficial effect on anxiety , ADHD , and DBD symptoms , regardless of the type of treatment received . There were no differential effects of medication or CBT on outcome , except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine . Clinical trial registration information-Treatment of SSRI-Resistant Depression In Adolescents ( TORDIA ) ; http:// clinical trials.gov/ ; NCT00018902 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 CONTEXT Volumetric studies have reported relatively decreased cortical thickness and gray matter volumes in adults with attention-deficit/hyperactivity disorder ( ADHD ) whose childhood status was retrospectively recalled . We present , to our knowledge , the first prospect i ve study combining cortical thickness and voxel-based morphometry in adults diagnosed as having ADHD in childhood . OBJECTIVES To test whether adults with combined-type childhood ADHD exhibit cortical thinning and decreased gray matter in regions hypothesized to be related to ADHD and to test whether anatomic differences are associated with a current ADHD diagnosis , including persistent vs remitting ADHD . DESIGN Cross-sectional analysis embedded in a 33-year prospect i ve follow-up at a mean age of 41.2 years . SETTING Research outpatient center . PARTICIPANTS We recruited prob and s with ADHD from a cohort of 207 white boys aged 6 to 12 years . Male comparison participants ( n = 178 ) were free of ADHD in childhood . We obtained magnetic resonance images in 59 prob and s and 80 comparison participants ( 28.5 % and 44.9 % of the original sample s , respectively ) . MAIN OUTCOME MEASURES Whole-brain voxel-based morphometry and vertexwise cortical thickness analyses . RESULTS The cortex was significantly thinner in ADHD prob and s than in comparison participants in the dorsal attentional network and limbic areas ( false discovery rate < 0.05 , corrected ) . In addition , gray matter was significantly decreased in prob and s in the right cau date , right thalamus , and bilateral cerebellar hemispheres . Prob and s with persistent ADHD ( n = 17 ) did not differ significantly from those with remitting ADHD ( n = 26 ) ( false discovery rate < 0.05 ) . At uncorrected P < .05 , individuals with remitting ADHD had thicker cortex relative to those with persistent ADHD in the medial occipital cortex , insula , parahippocampus , and prefrontal regions . CONCLUSIONS Anatomic gray matter reductions are observable in adults with childhood ADHD , regardless of the current diagnosis . The most affected regions underpin top-down control of attention and regulation of emotion and motivation . Exploratory analyses suggest that diagnostic remission may result from compensatory maturation of prefrontal , cerebellar , and thalamic circuitry OBJECTIVE The aim of this study was to examine the safety and efficacy of risperidone , with or without concomitant psychostimulant use , in the treatment of children with conduct disorder ( CD ) or other disruptive behavior disorders [ oppositional defiant disorder ( ODD ) , disruptive behavior disorder-not otherwise specified ( DBD-NOS ) ] , and comorbid attention-deficit hyperactivity disorder ( ADHD ) . METHODS Data from two 6-week placebo-controlled trials assessing risperidone therapy in children with subaverage IQs and CD , ODD , DBD-NOS were combined , and patients with comorbid ADHD were selected for this post hoc analysis . Patients were grouped according to r and omized drug therapy ( risperidone or placebo ) , and then subgrouped according to their use of a concomitant psychostimulant .  Safety outcomes included adverse events and weight change , while efficacy outcomes included changes in scores on disruptive behavior and hyperactivity-based subscales of two behavior-rating instruments ( Nisonger Child Behavior Rating Form and the Aberrant Behavior Checklist ) . RESULTS The analysis included 155 of 208 originally tested children divided into four sub-groups ( 35 - 43 patients each ) . There was no significant difference in the frequency of adverse events in patients who received  risperidone  alone and those who received risperidone plus a stimulant . The most common adverse events in risperidone-treated patients were somnolence , headache , dyspepsia , rhinitis , and vomiting . Within each r and omized treatment group , actual weight gain was comparable , regardless of concomitant stimulant use . Risperidone-treated patients had clinical ly and statistically significant reductions in both disruptive behavior and hyperactivity subscale scores , compared to placebo , regardless of concomitant stimulant use . The addition of risperidone to a psychostimulant result ed in significantly better control of hyperactivity ( p < 0.001 ) than was achieved with stimulant treatment alone , without causing an increase in adverse events . CONCLUSION Risperidone was a safe and effective treatment , with or without a combined psychostimulant , for both disruptive behavior disorders and comorbid ADHD in children 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 OBJECTIVE Recent studies have suggested that attention deficit hyperactivity disorder ( ADHD ) is associated with abnormalities in basal ganglia and prefrontal cortical functioning . However , these studies have primarily relied upon cognitive tasks that reflect impulse control rather than attentional mechanisms . METHOD The authors used functional magnetic resonance imaging to investigate the neural correlates of selective and divided attention in a r and omized , double-blind , placebo-controlled pharmacological challenge with methylpheni date in 15 adolescents with ADHD ( ages 14 - 17 ) , eight adolescents with reading disorder ( ages 12 - 17 ) , and four adolescents with both reading disorder and ADHD ( ages 14 - 18 ) who were scanned during both a methylpheni date and a placebo session . Fourteen healthy comparison subjects ( ages 12 - 20 ) who were not given methylpheni date served as the primary comparison group . RESULTS During the divided attention task , unmedicated subjects with ADHD or reading disorder  recruited the left ventral basal ganglia significantly less than the healthy comparison subjects . Methylpheni date led to an increase in activation in this region but had no effect on task performance .  Subjects with ADHD also recruited the middle temporal gyrus significantly less than the comparison subjects , but methylpheni date did not have a direct effect on activation in this region . CONCLUSIONS These results suggest that ADHD is associated with abnormal processing in attentional networks , with specific dysfunction in striatal circuitry . Methylpheni date may act to normalize activity within this network 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 Atomoxetine , a highly selective noradrenaline reuptake inhibitor ( SNRI ) , shows efficacy in the treatment of attention-deficit/hyperactivity disorder ( ADHD ) . Compared with psychostimulants , atomoxetine has a distinct mode of brain action and potentially lower addictive potential . Studies have yet to assess whether atomoxetine improves cognition following a single oral dose in ADHD . METHODS Twenty-two adults with DSM-IV ADHD were administered a single oral dose of atomoxetine ( 60 mg ) in a placebo-controlled double-blind crossover design . Cognitive effects were assessed using stop-signal , sustained attention , spatial working memory , and set-shifting paradigms . Normative cognitive data from 20 healthy volunteers were collected for comparison . RESULTS The ADHD patients under placebo conditions showed response inhibition and working memory deficits compared with healthy volunteers . Atomoxetine treatment in the ADHD patients was associated with shorter stop-signal reaction times and lower numbers of commission errors on the sustained attention task . CONCLUSIONS Atomoxetine improved inhibitory control , most likely via noradrenergically mediated augmentation of prefrontal cortex function . These results have implication s for underst and ing the mechanisms by which atomoxetine exerts beneficial clinical effects and suggest novel treatment directions for other disorders of impulsivity Background In this research the symptom improvement of attention-deficit hyperactivity disorder ( ADHD ) of children was assessed by oral vitamin D administration  in Tabriz , Iran . Methods In this double-blind , r and omized clinical trials , 96 children ( 2–18 years ) were enrolled to placebo and vitamin D groups . Children took vitamin D pearl ( 50,000 IU/week ) or placebo for 6 weeks . Children , who had the change in methylpheni date dosage and received any anticonvulsants and corticosteroids were excluded from the research . ADHD symptoms were diagnosed by Conners parent rating scale ( CPRS ) test at baseline and after intervention . ADHD Conners divided into inattention ( IA ) , hyperactivity/impulsivity ( H/I ) and combination type ( C ) subscales .  Vitamin D serum level was assessed at baseline and after 8 weeks in both groups . Results The differences between CPRS and its subscales were not significant at baseline ( P > 0.05 ) . The Conners IA score was decreased in vitamin D group ( P < 0.05 ; adjusted with age and baseline values ) . ADHD Conners and all subscale scores reduced remarkably after intervention in patients with insufficient level of vitamin D compared to placebo ( P < 0.05 ) . Conclusions Oral vitamin D  improved ADHD symptoms with a particular effect on inattention symptoms . In addition , symptoms related to all subscales were improved remarkably in patients with insufficient level of vitamin D. Vitamin D treatment in children with ADHD could be considered due to the exp and benefit of vitamin D in body CONTEXT Attention-deficit/hyperactivity disorder ( ADHD ) is a highly prevalent and impairing psychiatric disorder that affects both children and adults . There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD ; however , little is known about the mechanisms by which these different treatments exert their therapeutic effects . OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylpheni date hydrochloride vs the nonstimulant atomoxetine hydrochloride . DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylpheni date ( n = 18 ) or atomoxetine ( n = 18 ) using a parallel-groups design . SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine , New York , New York . PARTICIPANTS Thirty-six youth with ADHD ( mean [ SD ] age , 11.2 [ 2.7 ] years ; 27 boys ) recruited from r and omized clinical trials . MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version . RESULTS Treatment with methylpheni date vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean ( SD ) improvements in ratings of ADHD symptoms ( 55 % [ 30 % ] vs 57 % [ 25 % ] ) . Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments . Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylpheni date in the right inferior frontal gyrus , left anterior cingulate/supplementary motor area , and bilateral posterior cingulate cortex . These findings were not attributable to baseline differences in activation . CONCLUSIONS Treatment with methylpheni date and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions that have been implicated in the pathophysiology of ADHD . These results represent a first step in delineating the neurobiological basis of differential response to stimulant and nonstimulant medications for ADHD Background : Behavioral inhibition , which is a later-developing executive function ( EF ) and anatomically located in prefrontal areas , is impaired in attention-deficit and hyperactivity disorder ( ADHD ) . While optimal EFs have been shown to depend on efficient sleep in healthy subjects , the impact of sleep problems , frequently reported in ADHD , remains elusive . Findings of macroscopic sleep changes in ADHD are inconsistent , but there is emerging evidence for distinct microscopic changes with a focus on prefrontal cortical regions and non-rapid eye movement ( non-REM ) slow-wave sleep . Recently , slow oscillations ( SO ) during non-REM sleep were found to be less functional and , as such , may be involved in sleep-dependent memory impairments in ADHD . Objective : By augmenting slow-wave power through bilateral , slow oscillating transcranial direct current stimulation ( so-tDCS , frequency = 0.75 Hz ) during non-REM sleep , we aim ed to improve daytime behavioral inhibition in children with ADHD . Methods : Fourteen boys ( 10–14 years ) diagnosed with ADHD were included . In a r and omized , double-blind , cross-over design , patients received so-tDCS either in the first or in the second experimental sleep night . Inhibition control was assessed with a visuomotor go/no-go task .  Intrinsic alertness was assessed with a simple stimulus response task . To control for visuomotor performance , motor memory was assessed with a finger sequence tapping task . Results : SO-power was enhanced during early non-REM sleep , accompanied by slowed reaction times and decreased st and ard deviations of reaction times , in the go/no-go task after so-tDCS . In contrast , intrinsic alertness , and motor memory performance were not improved by so-tDCS . Conclusion : Since behavioral inhibition but not intrinsic alertness or motor memory was improved by so-tDCS , our results suggest that lateral prefrontal slow oscillations during sleep might play a specific role for executive functioning in ADHD 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 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 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 OBJECTIVE Co-morbid diagnoses , such as disruptive behavior disorders ( DBDs ) and high levels of aggression , are extremely common among youth with pediatric bipolar disorder ( PBD ) and may interfere with treatment response ; however , they have rarely been examined as predictors of response to pharmacotherapy . The current study examines co-morbid DBD and aggression prospect ively as predictors of pharmacotherapy outcome , as well as potential moderators of response to a specific medication ( risperidone vs. divalproex ) , among children with PBD . METHODS Data are from a prospect i ve 6-week double-blind , placebo-controlled , r and omized outpatient medication treatment trial of risperidone versus divalproex for manic episodes in 65 children 8 - 18 with PBD . Outcome measures were administered at pretest , post-test , and weekly during the 6 weeks of treatment . Mixed-effects regression models were used to examine pharmacotherapy response . RESULTS Results indicated that youth with co-morbid DBD experienced greater improvement in manic symptoms in response to risperidone versus divalproex , whereas youth with non-co-morbid DBD experienced similar trajectories of symptom improvement in both medication groups . In addition , the non-DBD group experienced greater improvement in global functioning over time as compared with youth with co-morbid-DBD , and this gap increased over the course of treatment . Results also indicated that high-aggression youth experienced worse global functioning by end treatment versus low-aggression youth . CONCLUSIONS In conclusion , a co-morbid diagnosis of DBD and /or high levels of aggressive symptoms in youth with PBD may be important clinical predictors of variation in treatment response to pharmacotherapy . These findings may help research ers and clinicians develop tailored treatment approaches that optimize symptom and functional outcomes INTRODUCTION Aggression is frequently observed in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . The aim of this study was to assess the efficacy with regard to oppositional and aggressive behavior of a new long-acting methylpheni date preparation ( Medikinet retard , MPH-MR ) , with equal portions of the immediate-release and the sustained-release active substance , and especially to look at correlations between either teacher or parent assessment of aggression and ADHD sub-symptomatology . METHODS Eighty five children and adolescents ( 6 - 16 years ) were investigated in a double-blind , r and omized , clinical trial over 5 weeks under a treatment with MPH-MR  using symptom checklists for ADHD , oppositional-defiant and conduct disorder according to the Diagnostic and Statistical Manual of Mental Disorders , 4th edition ( DSM-IV ) . RESULTS A total of 64.9 % of the children showed oppositional defiant disorder/conduct disorder ( ODD/CD ) symptoms . A statistically significant effect was found in the group treated with MPH ( verum-group ) . On the basis of Cohen 's criteria , high effects were found for aggressive symptoms in school ( d = 1.0 ) , but not in the afternoon ( d = 0.4 ) . There were also lower effect sizes for more severe aggressive symptoms . We found characteristic correlations between ODD/CD symptoms and the ADHD subscale hyperactivity/impulsivity compared to the subscale inattention . CONCLUSIONS Long-acting MPH is effective in the treatment of oppositional-defiant and aggressive behavior , especially concerning milder symptoms . The expected correlation between impulsivity and aggressiveness could be confirmed BACKGROUND Response inhibition is an executive function that requires voluntary control over responses when there is a change of context . The right inferior frontal cortex is necessary for response inhibition , and a deficit in right frontostriatal circuitry might underlie attention-deficit/hyperactivity disorder ( ADHD ) . Many studies of childhood ADHD have demonstrated impaired response inhibition and its amelioration by methylpheni date ( MPH ) . The current study tested response inhibition and the effect of MPH in adult ADHD . METHODS Response inhibition was assessed with the " tracking " stop-signal test in 13 adults with a diagnosis of ADHD , both while taking and while not taking medication , and 13 healthy , unmedicated , age- and intelligence quotient-matched control subjects . RESULTS Stop-signal reaction time was significantly slower in unmedicated adults with ADHD relative to healthy control subjects , and this deficit was significantly ameliorated by medication . CONCLUSIONS Adult ADHD patients had a response inhibition profile similar to that produced by lesions to the right inferior frontal cortex , which was remedied by stimulant medication The stimulant methylpheni date ( MPX ) and the nonstimulant atomoxetine ( ATX ) are the most commonly prescribed medications for attention deficit hyperactivity disorder ( ADHD ) . However , no functional magnetic resonance imaging ( fMRI ) study has as yet investigated the effects of ATX on inhibitory or any other brain function in ADHD patients or compared its effects with those of MPX . A r and omized , double-blind , placebo-controlled , crossover pharmacological design was used to compare the neurofunctional effects of single doses of MPX , ATX , and placebo during a stop task , combined with fMRI within 19 medication-naive ADHD boys , and their potential normalization effects relative to 29 age-matched healthy boys . Compared with controls , ADHD boys under placebo showed bilateral ventrolateral prefrontal , middle temporal , and cerebellar underactivation . Within patients , MPX relative to ATX and placebo significantly upregulated right ventrolateral prefrontal activation , which correlated with enhanced inhibitory capacity . Relative to controls , both drugs significantly normalized the left ventrolateral prefrontal underactivation observed under placebo , while MPX had a drug-specific effect of normalizing right ventrolateral prefrontal and cerebellar underactivation observed under both placebo and ATX . The findings show shared and drug-specific effects of MPX and ATX on performance and brain activation during inhibitory control in ADHD patients with superior upregulation and normalization effects of MPX 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 OBJECTIVE Electroencephalographic ( EEG ) neurofeedback ( NF ) is considered a nonpharmacological alternative for medication in attention-deficit/hyperactivity disorder ( ADHD ) . Comparisons of the behavioral efficacy of NF and medication have produced inconsistent results . EEG measures can provide insight into treatment mechanisms , but have received little consideration . In this r and omized controlled trial ( RCT ) , effects of NF were compared with methylpheni date ( MPH ) , and physical activity ( PA ) in children with ADHD on event-related potential ( ERP ) indices of response inhibition , which are involved in ADHD psychopathology . METHODS Using a multicenter three way parallel group RCT design , 112 children with a Diagnostic and Statistical Manual of Mental Disorders , 4th ed . ( DSM-IV ) ( American Psychiatric Association 1994 ) diagnosis of ADHD , between 7 and 13 years of age , were initially included .  NF training consisted of 30 sessions of theta/beta training at Cz over a 10 week period . PA training was a semiactive control group , matched in frequency and duration . MPH was titrated using a double-blind placebo controlled procedure in 6 weeks , followed by a stable dose for 4 weeks . ERP measures of response inhibition , N2 and P3 , were available for 81 children at pre- and postintervention ( n = 32 NF , n = 25 MPH , n = 24 PA ) . RESULTS Only the medication group showed a specific increase in P3 amplitude compared with NF ( partial eta-squared [ ηp(2 ) ] = 0.121 ) and PA ( ηp(2 ) = 0.283 ) , which was related to improved response inhibition . Source localization of medication effects on P3 amplitude indicated increased activation primarily in thalamic and striatal nuclei . CONCLUSIONS This is the first study that simultaneously compared NF with stimulant treatment and a semiactive control group . Only stimulant treatment demonstrated specific improvements in brain function related to response inhibition . These results are in line with recent doubts on the efficacy and specificity of NF as treatment for ADHD . CLINICAL TRIALS REGISTRATION Train Your Brain ? Exercise and Neurofeedback Intervention for ADHD , https:// clinical trials.gov/show/NCT01363544 , Ref . No. NCT01363544
Results : In ADHD , deviant prefrontal and cingulate functional activity was associated with increased IA .
Structural alterations were most pronounced in the cingulate cortex .
Subjects with DBDs showed marked cortico‐subcortical dysfunctions .
ADHD and DBDs share similar cortico‐limbic structural and functional alterations .
RI deficits in ADHD highlighted hypoactivity in the dorso/ventro‐lateral PFC , insula , and striatum , while the paralimbic system was primarily dysfunctional in DBDs .
Across disorders , extensively altered cortico‐limbic dysfunctions underlie IA , while RI was mostly associated with aberrant prefrontal activity .
Conclusion : Control network deficits were evidence d across clinical phenotypes in IA and RI .
Dysfunctions at any level within these cortico‐subcortical projections lead to deficient cognitive‐affective control by ascribing emotional salience to otherwise irrelevant stimuli .
HighlightsImpulsive aggression and dysfunctional response inhibition are present in ADHD and DBDs .
Broad fronto‐striatal‐cerebellar dysfunctions have been implicated in ADHD and DBDs .
Prefrontal and cingulate cortical deficits are associated with IA in ADHD.Severe widespread cortico‐subcortical breakdowns are associated with IA in DBDs .
RI deficits have been attributed to hypoactivity in the lateral PFC , insula , and amygdala .
Whether reduced gray matter volumes relate to ADHD and DBDs or if present as an IA epiphenomenon remains debatable .
Background : Although impulsive aggression ( IA ) and dysfunctional response inhibition ( RI ) are hallmarks of attention‐deficit/hyperactivity disorder ( ADHD ) and disrupted behavioral disorders ( DBDs ) , little is known about their shared and distinct deviant neural mechanisms .