title: Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder Caffeine effects on resting-state electrodermal levels in AD/HD suggest an anomalous arousal mechanism Timing of caffeine's impact on autonomic and central nervous system measures: Clarification of arousal effects Methylphenidate effects in attention deficit/hyperactivity disorder: electrodermal and ERP measures during a continuous performance task Methylphenidate improves diminished error and feedback sensitivity in ADHD: An Evoked Heart Rate analysis Caffeine effects on resting-state arousal Responses to methylphenidate in adolescent AD/HD: evidence from concurrently recorded autonomic (EDA) and central (EEG and ERP) measures.
abstract: 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 effect of a single oral dose of caffeine was examined in a r and omised double-blind placebo-controlled repeated- measures cross-over study . Eighteen children with AD/HD , aged between 8 and 13 years , were individually age- and gender-matched with a control group . All children participated in two sessions , one week apart . Skin conductance level ( SCL ) from a 3 min eyes-closed epoch , commencing 30 min after ingestion of caffeine or placebo , was examined . Across conditions , mean SCL was lower in the AD/HD group than controls , confirming hypoarousal in AD/HD . Caffeine produced an increase in SCL , and this increase did not differ between the groups . However , arousal increases were dose-dependent in controls , but not in AD/HD . Rather , caffeine-induced arousal increases in the AD/HD group were positively related to their hyperactivity/impulsivity levels . This suggests an anomalous arousal mechanism in AD/HD functionally related to impairment in one symptom dimension The timing of  caffeine  effects on arousal levels  was examined . From previous work in our laboratory , an increase in skin conductance level ( SCL ) was used as the marker of arousal increase , and we sought to identify the timing of this and related effects following caffeine ingestion . A single oral dose of caffeine ( 250 mg ) was used in a r and omised double-blind placebo-controlled repeated- measures cross-over study . Eyes-closed resting electroencephalogram ( EEG ) and autonomic data ( SCL , heart rate , respiration rate , and systolic and diastolic blood pressure ) during 2 min epochs that commenced every 4 min after ingestion , were analysed . The SCL placebo data were used to identify potential arousal measures prior to examining caffeine effects . Caffeine was associated with increased SCL , increased respiratory rate and a global reduction in alpha power . There were no significant cardiovascular effects of caffeine-induced arousal . These caffeine results are consistent with our recent electrodermal and EEG studies of arousal , and confirm the potential use of caffeine as a simple means of experimentally modifying arousal levels without task-related confounds Rationale Previous research investigating the effects of stimulants , such as methylpheni date ( MPH ) , on children with attention deficit/hyperactivity disorder ( AD/HD ) has rarely included autonomic measures of arousal . Objective Our aim was to clarify the effects of MPH on central and autonomic measures in AD/HD children during a continuous performance task ( CPT ) using a naturalistic open-label study . Method Thirty-six boys ( 18 AD/HD and 18 control ) participated in a CPT over two trial periods , allowing a more valid estimate of the effects of medication , rather than assuming that retesting per se has no substantial impact . MPH was administered to the AD/HD group 1 h prior to the second trial . Errors and reaction time ( RT ) were recorded as measures of performance , electrodermal activity as an autonomic nervous system measure and event-related potentials ( ERPs ) as an index of central nervous system activity . Results AD/HD children made more errors than controls in the first session , but no group differences were found after medication . No significant differences were observed for RT . Skin conductance level was found to be lower in AD/HD children than controls , but this difference was also ameliorated after medication . Conversely , mean skin conductance response to target stimuli was found not to differ between groups during the initial test phase but became significantly different in phase 2 . ERP data showed topographic differences between groups in N1 , P2 , N2 and P3 at the initial test phase , which were reduced at the second test . ConclusionS timulant medication ameliorated some of the dysfunctions in AD/HD children , which are reflected in behavioural and ERP measures . These results , in combination with general differences in electrodermal activity , support a hypoarousal model of AD/HD , which can explain the action of MPH in these children 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 This study examined the use of caffeine to manipulate arousal level without the confounds associated with task-related activation . From previous work in our laboratory , an increase in skin conductance level ( SCL ) and EEG alpha frequency , together with a global decrease in alpha power , were used as markers of arousal increase , and we sought to identify these effects with caffeine ingestion . METHODS We examined the effect of a single oral dose of caffeine ( 250 mg ) in a r and omised double-blind placebo-controlled repeated- measures cross-over study . Eighteen healthy university students ( mean age 21 years ; 13/18 females ) participated in two sessions 1 week apart . EEG and autonomic data ( SCL , heart rate , systolic and diastolic blood pressure , and respiration rate ) from a 2 min eyes-closed epoch , commencing approximately 30 min after ingestion of caffeine or placebo , were examined . RESULTS Caffeine was associated with increased SCL , a global reduction in EEG power in the alpha b and , and a global increase in alpha frequency . There were no cardiovascular effects . CONCLUSIONS The positive results are consistent with recent electrodermal and EEG studies of arousal and suggest that caffeine may be utilised as a task-free means of manipulating arousal in future investigations . Further work is necessary to clarify the absence of cardiovascular effects , and to integrate those data with emerging conceptualisations of arousal and activation . SIGNIFICANCE The present data support the use of caffeine as a simple tool to explore the role of arousal in both normal and atypical functioning , and this may be useful in determining the validity and importance of supposed hyper- or hypo-arousal in such syndromes as attention-deficit/hyperactivity disorder ( AD/HD ) This paper aims to examine the effects of methylpheni date ( MPH ) on integrated baseline and event-related psychophysiological measures in AD/HD . Thirty-four unmedicated AD/HD adolescents ( 11 - 17 years ; 6 females ) were first compared to 34 age- and sex-matched controls , and then re-tested at least 4 weeks after methylpheni date ( MPH ) medication .  In each testing session , EDA was recorded simultaneously with EEG during a resting eyes open condition , and with ERPs during an auditory oddball task . Unmedicated AD/HD subjects were compared to controls and then AD/HD subjects were compared pre- and post-medication . Correlations between the change in EEG theta and the remaining psychophysiological variables were undertaken to provide information about post MPH treatment changes . In the unmedicated state , AD/HD was characterized by abnormally enhanced theta , across fronto- central sites , generally reduced P2 responses , with larger non-specific and oddball-elicited SCRs and poor behavioural performance on the oddball task . Following treatment , AD/HD showed a ' normalization ' of theta activity ( particularly in the right hemisphere ) , a reduction in the rate of decrement of EDA and a general increase in P3 amplitude . These findings suggest that methylpheni date is associated with a robust ' normalization ' of low frequency EEG activity during the resting brain state , but has less impact on task-related brain activity or phasic changes in autonomic function . This dissociation of resting and task-related activity may prove to be useful in elucidating the effects of stimulant versus new non-stimulant medications in AD/HD
target: 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 .
background: 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 .