Reduced Prefrontal Gyrification in Carriers of the Dopamine D4 Receptor 7-Repeat Allele With Attention Deficit/Hyperactivity Disorder: A Preliminary Report.

Objective: Structural and functional abnormalities have been noted in the prefrontal cortex of individuals with neurodevelopmental disorders such as attention deficit/hyperactivity disorder (ADHD). Cortical thickness and gyrification, both of which have been reported as abnormal in the prefrontal cortex in ADHD, are thought to be modulated by genetic influences during neural development. This study aimed to investigate the effects of a polymorphism of the dopamine DRD4 gene (the 7-repeat (7R) "risk" allele) on thickness and gyrification as distinct parameters of prefrontal cortical structure in children with ADHD. Method: Structural images and genetic samples were obtained from 49 children aged 9-15 years (25 with ADHD and 24 matched controls), and measures of cortical thickness and gyrification for inferior, middle, and superior frontal cortex were calculated. Results: A significant interaction between diagnosis and genotype on prefrontal gyrification was observed, largely driven by reduced inferior frontal gyrification in patients who carried the DRD4 7R allele. Furthermore, inferior frontal gyrification-but not thickness-related to everyday executive functioning in 7R allele carriers across groups. Conclusions: Prefrontal gyrification is reduced in children with ADHD who also carry the DRD4 7R allele, and it relates to critical functional skills in the executive domain in carriers of the risk allele. More broadly, these effects highlight the importance of considering precise neurodevelopmental mechanisms through which risk alleles influence cortical neurogenesis and migration.

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.

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.

Implementing routine outcome measures in child and adolescent mental health services: from present to future practice.

BACKGROUND: Routine outcome measurement (ROM) in CAMHS is supported by U.K. Government policy. However, little is known about how measures are used in practice. METHOD: Data describing use of ROM, knowledge and attitudes regarding implementation were collected using a regional case-note audit, online survey and stakeholder workshop. RESULTS: While the principle of ROM was supported by stakeholders, baseline and follow-up outcome measurement occurred in less than a fifth of cases. Barriers to implementation included lack of training and resources, clinicians' perceptions of the limitations of existing measures and lack of regular feedback of outcome data. CONCLUSIONS: Implementation of ROM may be facilitated by session-by-session measures with immediate feedback to clinicians and patients.

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.

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).

BACKGROUND: Low 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/DESIGN: A 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. DISCUSSION: We 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 REGISTRATION: ISRCTN Register no. ISRCTN12650001.

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.

Cortical gray matter in attention-deficit/hyperactivity disorder: a structural magnetic resonance imaging study.

OBJECTIVE: Previous studies have shown smaller brain volume and less gray matter in children with attention-deficit/hyperactivity disorder (ADHD). Relatively few morphological studies have examined structures thought to subserve inhibitory control, one of the diagnostic features of ADHD. We examined one such region, the pars opercularis, predicting a thinner cortex of the inferior frontal gyrus (IFG) in children with ADHD. METHOD: Structural images were obtained from 49 children (24 control; 25 ADHD combined subtype) aged 9 though 15 years. Images were processed using a volumetric pipeline to provide a fully automated estimate of regional volumes of gray and white matter. A further analysis using FreeSurfer provided measures of cortical thickness for each lobe, and for 13 regions in the frontal lobe. RESULTS: Relative to controls, children with ADHD had smaller whole brain volume and lower gray matter, but not white matter, volumes in all lobes. An analysis of frontal regions showed a significant interaction of group by region. Planned contrasts showed bilateral thinner cortex in the pars opercularis in children with ADHD. CONCLUSIONS: Children with ADHD showed both diffuse and regional gray matter abnormalities. Consistent with its putative role in response inhibition, the cortex of the pars opercularis was thinner in children with ADHD who, as expected, had significantly poorer inhibitory performance on a Go/No-go task. These differences held for both hemispheres raising the possibility that a developmental abnormality of IFG might drive development of inhibition difficulties.

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.

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.

The Social Aptitudes Scale: an initial validation.

BACKGROUND: Poor social skills are associated with a range of child and adolescent psychiatric disorders, with deficits being particularly marked in autistic spectrum disorders (ASDs). Here, we validate a brief measure of social aptitudes where low scores are designed to index a substantially raised risk of ASDs. METHOD: Parents of a national community sample of 7,977 British 5-16 year olds completed the Social Aptitudes Scale (SAS) as well as a general questionnaire measure of psychopathology, the Strengths and Difficulties Questionnaire (SDQ). Psychiatric diagnoses were assigned by clinical raters on the basis of detailed multi-informant information. RESULTS: All ten items of the SAS loaded onto a single latent factor, with a Cronbach's alpha of 0.88. Correlations between the SAS and the SDQ were only modest, suggesting that the SAS measures different attributes to the SDQ. The SAS was significantly better than the SDQ at identifying ASDs. CONCLUSION: Children and adolescents with low SAS scores are at increased risk of mental health problems, particularly ASDs.

Relaxation strategies and enhancement of hypnotic susceptibility: EEG neurofeedback, progressive muscle relaxation and self-hypnosis.

Hypnosis has been shown to be efficacious in a range of clinical conditions, including the management of chronic pain. However, not all individuals are able to enter a hypnotic state, thereby limiting the clinical utility of this technique. We sought to determine whether hypnotic susceptibility could be increased using three methods thought to facilitate relaxation, with particular interest in an EEG neurofeedback protocol which elevated the theta to alpha ratio. This was compared with progressive muscle relaxation and self-hypnosis. Ten subjects with moderate levels of susceptibility (2-7/12) were randomly assigned to each condition and assessed for hypnotic susceptibility prior to and upon completion of 10 sessions of training. Hypnotic susceptibility increased post-training in all groups, providing further evidence that operant control over the theta/alpha ratio is possible, but contrary to our predictions, elevation of the theta/alpha ratio proved no more successful than the other interventions. Nonetheless, all three techniques successfully enhanced hypnotic susceptibility in over half of the participants (17/30), a similar incidence to that reported using other methods. As previously reported, the majority who were not susceptible to modification were at the lower levels of susceptibility, and the greater increases tended to occur in the more susceptible subjects. However, here enhancement was disclosed in some at low levels, and capability was found of reaching high levels, both features not typically reported. Further research is warranted.

Abstract stimuli associated with threat through conditioning cannot be detected preattentively.

Studies of anxiety suggest that threat stimuli can be identified preattentively, but this conclusion is questionable because of possible low-level perceptual confounds. Two experiments used visual search tasks in which abstract shapes were conditioned to carry neutral or negative valence. Experiment 1 found generally faster responses to threat-associated abstract stimuli but no evidence that they were detected preattentively, irrespective of trait anxiety level. A similar pattern was found in Experiment 2, in which individuals high in snake or spider fear showed no evidence of preattentive detection of abstract stimuli associated with their feared object. In contrast, implicit behavioral measures showed significant effects of conditioning, demonstrating that targets associated with threat were negatively evaluated in these experiments.