We describe almost entirely automated procedures for estimation of global, voxel, and cluster-level statistics to test the null hypothesis of zero neuroanatomical difference between two groups of structural magnetic resonance imaging (MRI) data. Theoretical distributions under the null hypothesis are available for 1) global tissue class volumes; 2) standardized linear model [analysis of variance (ANOVA and ANCOVA)] coefficients estimated at each voxel; and 3) an area of spatially connected clusters generated by applying an arbitrary threshold to a two-dimensional (2-D) map of normal statistics at voxel level. We describe novel methods for economically ascertaining probability distributions under the null hypothesis, with fewer assumptions, by permutation of the observed data. Nominal Type I error control by permutation testing is generally excellent; whereas theoretical distributions may be over conservative. Permutation has the additional advantage that it can be used to test any statistic of interest, such as the sum of suprathreshold voxel statistics in a cluster (or cluster mass), regardless of its theoretical tractability under the null hypothesis. These issues are illustrated by application to MRI data acquired from 18 adolescents with hyperkinetic disorder and 16 control subjects matched for age and gender.

ADHD is associated with subnormal activation of the prefrontal systems responsible for higher-order motor control. Functional MRI is a feasible technique for investigation of neural correlates of ADHD.

Quality of life (QoL) describes an individual’s subjective perception of their position in life as evidenced by their physical, psychological, and social functioning. QoL has become an increasingly important measure of outcome in child mental health clinical work and research. Here we provide a systematic review of QoL studies in children and young people with attention deficit hyperactivity disorder (ADHD) and address three main questions. (1) What is the impact of ADHD on QoL? (2) What are the relationships between ADHD symptoms, functional impairment and the mediators and moderators of QoL in ADHD? (3) Does the treatment of ADHD impact on QoL? Databases were systematically searched to identify research studies describing QoL in ADHD. Thirty six relevant articles were identified. Robust negative effects on QoL are reported by the parents of children with ADHD across a broad range of psycho-social, achievement and self evaluation domains. Children with ADHD rate their own QoL less negatively than their parents and do not always seeing themselves as functioning less well than healthy controls. ADHD has a comparable overall impact on QoL compared to other mental health conditions and severe physical disorders. Increased symptom level and impairment predicts poorer QoL. The presence of comorbid conditions or psychosocial stressors helps explain these effects. There is emerging evidence that QoL improves with effective treatment. In conclusion, ADHD seriously compromises QoL especially when seen from a parents’ perspective. QoL outcomes should be included as a matter of course in future treatment studies.

Inhibitory and performance-monitoring functions have been shown to develop throughout adolescence. The developmental functional magnetic resonance imaging (fMRI) literature on inhibitory control, however, has been relatively inconsistent with respect to functional development of prefrontal cortex in the progression from childhood to adulthood. Age-related performance differences between adults and children have been shown to be a confound and may explain inconsistencies in findings. The development of error-related processes has not been studied so far using fMRI. The aim of this study was to investigate the neural substrates of the development of inhibitory control and error-related functions by use of an individually adjusted task design that forced subjects to fail on 50% of trials, and therefore controlled for differences in task difficulty and performance between different age groups. Event-related fMRI was used to compare brain activation between 21 adults and 26 children/adolescents during successful motor inhibition and inhibition failure. Adults compared with children/adolescents showed increased brain activation in right inferior prefrontal cortex during successful inhibition and in anterior cingulate during inhibition failure. A whole-brain age-regression analysis between 10 and 42 years showed progressive age-related changes in activation in these two brain regions, with additional changes in thalamus, striatum, and cerebellum. Age-correlated brain regions correlated with each other and with inhibitory performance, suggesting they form developing fronto-striato-thalamic and fronto-cerebellar neural pathways for inhibitory control. This study shows developmental specialization of the integrated function of right inferior prefrontal cortex, basal ganglia, thalamus, and cerebellum for inhibitory control and of anterior cingulate gyrus for error-related processes.

The study shows that abnormal brain activation during inhibitory challenge in ADHD is specific to the disorder, since it persists when medication history and performance discrepancies are excluded.