Martin J. Batty

Task-Related Default Mode Network Modulation and Inhibitory Control in ADHD: Effects of Motivation and Methylphenidate.

BACKGROUND Deficits characteristic of attention deficit/hyperactivity disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the default mode network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. METHOD We obtained functional magnetic resonance images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. RESULTS When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off-methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. CONCLUSIONS During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.

Effects of Motivation and Medication on Electrophysiological Markers of Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder

Background Theories of attention-deficit/hyperactivity disorder (ADHD) posit either executive deficits and/or alterations in motivational style and reward processing as core to the disorder. Effects of motivational incentives on electrophysiological correlates of inhibitory control and relationships between motivation and stimulant medication have not been explicitly tested. Methods Children (9–15 years) with combined-type ADHD (n = 28) and matched typically developing children (CTRL) (n = 28) performed a go/no-go task. Electroencephalogram data were recorded. Amplitude of two event-related potentials, the N2 and P3 (markers of response conflict and attention), were measured. The ADHD children were all stimulant responders tested on and off their usual dose of methylphenidate; CTRLs were never medicated. All children performed the task under three motivational conditions: reward; response cost; and baseline, in which points awarded/deducted for inhibitory performance varied. Results There were effects of diagnosis (CTRL > ADHD unmedicated), medication (on > off), and motivation (reward and/or response cost > baseline) on N2 and P3 amplitude, although the N2 diagnosis effect did not reach statistical significance (p = .1). Interactions between motivation and diagnosis/medication were nonsignificant (p > .1). Conclusions Motivational incentives increased amplitudes of electrophysiological correlates of response conflict and attention in children with ADHD, towards the baseline (low motivation) amplitudes of control subjects. These results suggest that, on these measures, motivational incentives have similar effects in children with ADHD as typically developing CTRLs and have additive effects with stimulant medication, enhancing stimulus salience and allocation of attentional resources during response inhibition.

Autistic spectrum disorder traits in children with attention deficit hyperactivity disorder.

BACKGROUND Current classification systems do not allow for comorbid diagnoses of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). Children with ADHD are often screened for ASD during clinical assessment and when recruited to clinical trials. We predicted that children with ADHD would have more autistic traits than controls and that certain traits would be more prevalent. METHODS The clinically referred sample consisted of 30 children with ADHD and 30 matched controls aged 9-15 years. Children were screened for ASD traits using the Social Aptitudes Scale (SAS) and the Social Communication Questionnaire (SCQ). RESULTS We found that ASD traits were significantly higher in children with ADHD than controls. None of the children received a diagnosis of autism or ASD. However, a large proportion (28% using the SCQ and 62% using the SAS) of children with ADHD reached screening thresholds for a predictive diagnosis of ASD. Relative to controls, children with ADHD had significantly higher levels of communication and social deficits, but not repetitive behaviours. CONCLUSION Further work is needed to establish whether autistic-like communication and social difficulties in children with ADHD are part of the broader ASD phenotype or are specific to ADHD.

Looking before you leap: A theory of motivated control of action

The acquisition of volitional control depends, in part, on developing the ability to countermand a planned action. Many tasks have been used to tap the efficiency of this process, but few studies have investigated how it may be modulated by participants’ motivation. Multiple mechanisms may be involved in the deliberate exercise of caution when incentives are provided. For example, control may involve modulation of the efficiency of the countermanding process, and/or inhibitory modulation of the impulse to go. One of the most commonly used paradigms to assess control of action is the Stop Signal Task, in which a primary Go stimulus is occasionally followed by a countermanding Stop signal, allowing a Stop Signal Reaction Time (SSRT) to be inferred as the outcome of a “horse race” between the go and countermanding processes. Here, we present a computational model in which high task motivation modulates proactive pre-stimulus inhibition of the go response. This allows responses to be calibrated so as to fall within a time-window that maximizes the probability of success, regardless of trial type, but does not decrease the observed SSRT. We report empirical support for the model from a sample of typically developing children, and discuss the broader implications for operationalizing measures of volitional control.

Motivational incentives and methylphenidate enhance electrophysiological correlates of error monitoring in children with attention deficit/hyperactivity disorder

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. Methylphenidate (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.

Morphological abnormalities in prefrontal surface area and thalamic volume in attention deficit/hyperactivity disorder.

Although previous morphological studies have demonstrated abnormalities in prefrontal cortical thickness in children with attention deficit/hyperactivity disorder (ADHD), studies investigating cortical surface area are lacking. As the development of cortical surface is closely linked to the establishment of thalam-ocortical connections, any abnormalities in the structure of the thalamus are likely to relate to altered cortical surface area. Using a clinically well-defined sample of children with ADHD (n=25, 1 female) and typically developing controls (n=24, 1 female), we studied surface area across the cortex to determine whether children with ADHD had reduced thalamic volume that related to prefrontal cortical surface area. Relative to controls, children with ADHD had a significant reduction in thalamic volume and dorsolateral prefrontal cortical area in both hemispheres. Furthermore, children with ADHD with smaller thalamic volumes were found to have greater reductions in surface area, a pattern not evident in the control children. Our results are further evidence of reduced lateral prefrontal cortical area in ADHD. Moreover, for the first time, we have also shown a direct association between thalamic anatomy and frontal anatomy in ADHD, suggesting the pathophysiological process that alters surface area maturation is likely to be linked to the development of the thalamus.

Evaluating the effectiveness of a schools-based programme to promote exercise self-efficacy in children and young people with risk factors for obesity: steps to active kids (STAK).

BackgroundLow levels of physical activity in children have been linked to an increased risk of obesity, but many children lack confidence in relation to exercise (exercise self-efficacy). Factors which can impact on confidence include a chronic health condition such as asthma, poor motor skills and being overweight. Increasing levels of physical activity have obvious benefits for children with asthma and children who are overweight, but few activity interventions with children specifically target children with low exercise self-efficacy (ESE). This study aims to evaluate the efficacy and feasibility of a schools-based activity programme suitable for children with risk factors for adult obesity, including asthma, overweight and low exercise self-efficacy.Methods/DesignA clustered (at the level of school) RCT will be used to compare a targeted, 10 week, stepped activity programme (activity diary, dance DVD, circuit-training and motivational interviewing) designed to promote ESE. We will recruit 20 primary schools to participate in the intervention and 9-11 year old children will be screened for low levels of ESE, asthma and overweight. In order to provide sufficient power to detect a difference in primary outcomes (Body Mass Index-BMI & ESE at 12 month follow-up) between children in the intervention schools and control schools, the target sample size is 396. Assessments of BMI, ESE, waist circumference, peak flow, activity levels and emotional and behavioural difficulties will be made at baseline, 4 months and 12 month follow-up.DiscussionWe aim to increase ESE and levels of physical activity in children with risk factors for adult obesity. The outcomes of this study will inform policy makers about the feasibility, acceptability and effectiveness of delivering targeted health interventions within a school setting.Trial RegistrationISRCTN Register no. ISRCTN12650001

Protocol Evaluating the effectiveness of a school-based group programme for parents of children at risk of ADHD: the ‘PArents, Teachers and CHildren WORKing Together (PATCHWORK)’ cluster RCT protocol

Introduction Early intervention for childhood behavioural problems may help improve health and educational outcomes in affected children and reduce the likelihood of developing additional difficulties. The National Institute for Health and Clinical Excellence guidelines for attention deficit/hyperactivity disorder (ADHD), a common childhood behavioural disorder, recommend a stepped care approach for the identification and management of these problems. Parents of children with high levels of hyperactivity and inattention may benefit from intervention programmes involving behavioural management and educational approaches. Such interventions may be further enhanced by providing training and feedback to teachers about the strategies discussed with parents. In relation to children with high levels of hyperactivity, impulsiveness and inattention, we aim to test the feasibility and effectiveness of a parenting programme (with and without an accompanying teacher session) in primary schools. Methods and analysis This clustered (at the level of school) randomised controlled trial (RCT) focuses on children in their first four school years (ages 4–8 years) in the East Midlands area of England. Parents will complete a screening measure, the Strengths and Difficulties Questionnaire, to identify children with high levels of hyperactivity/inattention. Three approaches to reducing hyperactivity and attention problems will be compared: a group programme for parents (parent-only intervention); group programme for parents combined with feedback to teachers (combined intervention); and waiting list control (no intervention). Differences between arms on the short version of Conners’ Parent and Teacher Rating Scales Revised will be compared and also used to inform the sample size required for a future definitive cluster RCT. A preliminary cost-effectiveness analysis will also be conducted. Ethics and dissemination The outcomes of this study will inform policy makers about the feasibility, acceptability and effectiveness of delivering targeted behavioural interventions within a school setting. The study has received ethical approval from the University of Nottingham Medical School Ethics Committee. Trial registration ISRCTN87634685

48 Cluster-Randomised Trial of a Targeted Intervention to Promote Exercise Self-Efficacy and Reduce Bmi in Children at Risk of Obesity

Background and aims Being physically active can help to reduce the risk of obesity in later life. This study aimed to evaluate the effectiveness of a targeted, school-based intervention (Steps to Active Kids - STAK) in improving exercise self-efficacy and reducing BMI in children. Method STAK is a 12 week, activity programme including activity diary, street dance DVD, circuit training and, for children at or above the 91st centile weight for height, motivational interviewing and goal setting. STAK was evaluated in a cluster-randomised trial in 24 schools. Children aged 9 to 11 were screened for overweight, low exercise self-efficacy or asthma. Twelve schools were randomised to receive the STAK intervention and 12 to control. BMI, waist circumference and exercise self-efficacy were assessed at baseline and post intervention (4 months). Results Of the 2479 children screened, 1065 children (43%) met the study inclusion criteria. Parents of 424 (40%) children consented to their child’s participation with 4 months follow-up data available for 392 (92%). The groups were well matched at baseline. After controlling for baseline values and time between testing, children in the intervention group had higher total self-efficacy at 4 month follow-up. In the group of children who were overweight at baseline (=>91st centile), those in the STAK intervention group had smaller waist circumference and lower BMI at 4 month follow-up. Conclusion Preliminary analysis suggests that a targeted activity intervention has benefits for children at risk of obesity. Future analyses will explore if benefits are sustained at 12 months follow-up.