Distributed grey and white matter deficits in hyperkinetic disorder: MRI evidence for anatomical abnormality in an attentional network.

BACKGROUND: Previous neuroimaging studies of children with attention deficit hyperactivity disorder (ADHD) have demonstrated anatomic and functional abnormalities predominantly in frontal and striatal grey matter. Here we report the use of novel image analysis methods, which do not require prior selection of regions of interest, to characterize distributed morphological deficits of both grey and white matter associated with ADHD. METHODS: Eighteen children with a refined phenotype of ADHD, who also met ICD-10 criteria for hyperkinetic disorder (mean age 10.4 years), and 16 normal children (mean age 10.3 years) were compared using magnetic resonance imaging. The groups were matched for handedness, sex, height, weight and head circumference. Morphological differences between groups were estimated by fitting a linear model at each voxel in standard space, applying a threshold to the resulting voxel statistic maps to generate clusters of spatially contiguous suprathreshold voxels, and testing cluster 'mass', or the sum of suprathreshold voxel statistics in each 2D cluster, by repeated random resampling of the data. RESULTS: The hyperkinetic children had significant grey matter deficits in right superior frontal gyrus (Brodmann area (BA) 8/9), right posterior cingulate gyrus (BA 30) and the basal ganglia bilaterally (especially right globus pallidus and putamen). They also demonstrated significant central white matter deficits in the left hemisphere anterior to the pyramidal tracts and superior to the basal ganglia. CONCLUSIONS: This pattern of spatially distributed grey matter deficit in the right hemisphere is compatible with the hypothesis that ADHD is associated with disruption of a large scale neurocognitive network for attention. The left hemispheric white matter deficits may be due to dysmyelination.

Neuropsychological analyses of impulsiveness in childhood hyperactivity.

BACKGROUND: Neuropsychological analyses of impulsiveness are needed to refine assessment of attention-deficit hyperactivity disorder (ADHD). AIMS: To investigate specific impairments in hyperactive children in a neuropsychological task battery of impulsiveness, the Maudsley Attention and Response Suppression (MARS) task battery, and to identify the neural substrates. METHOD: Impulsiveness was assessed using different tasks of inhibitory control and time management (MARS) in 55 children with ADHD, other diagnoses and controls. Functional magnetic resonance images were obtained from adolescents with and without ADHD during three of the tasks. RESULTS: Children with ADHD, but not psychiatric controls, were impaired on tests of response inhibition, but not of motor timing. Reduced right prefrontal activation was observed in hyperactive adolescents during higher level inhibition and delay management, but not during simple sensorimotor coordination. CONCLUSIONS: Attention-deficit hyperactivity disorder is characterised by specific deficits in tasks of motor response inhibition, but not motor timing, and by dysfunction of frontostriatal brain regions.

Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks.

Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.

Corpus callosum may be similar in children with ADHD and siblings of children with ADHD.

No previous studies have used morphological neuroimaging to compare children with ADHD with siblings of children with ADHD. To test the hypothesis that the total size of the corpus callosum is altered in children with hyperkinetic disorder, the corpus callosum was outlined from a single midline protondensity weighted slice (containing the septum pellucidum). Fifteen boys with a refined phenotype of ADHD (mean age 10.2 years) and 15 healthy male siblings of children with ADHD (mean age 10.6 years) were enrolled in the study. The two groups were compared for global brain size and the callosal areas of Witelson. No significant differences were found between the study and comparison groups for any of the corpus callosum areas, even after age, global brain size, and handedness were covaried (using MANOVA). In addition, corpus callosum sizes do not seem to differ between children with ADHD and unaffected siblings of children with ADHD. Clinicians should not base their pathophysiological diagnosis of this disorder on an abnormality of callosal development.

Functional frontalisation with age: mapping neurodevelopmental trajectories with fMRI.

The aim of this study was to investigate whether previously observed hypofrontality in adolescents with attention deficit-hyperactivity disorder (ADHD) during executive functioning [Rubia K, Overmeyer S, Taylor E, Brammer M, Williams S, Simmons A, Andrew C, Bullmore ET. Hypofrontality in attention deficit hyperactivity disorder during higher order motor control: a study using fMRI. Am J Psychiatry 1999;156(6):891-896] could be attributed to delayed maturation of frontal cortex. Brain activation of 17 healthy subjects, 9 adolescents and 8 young adults, during performance of a motor response inhibition task and a motor timing task was measured using functional magnetic resonance imaging (fMRI). The effect of age on brain activation was estimated, using the analysis of variance and regression, at both voxel and regional levels. In the delay task, superior performance in adults was paralleled by a significantly increased power of response in a network comprising prefrontal and parietal cortical regions and putamen. In the stop task, alternative neuronal routes--left hemispheric prefrontal regions in adults and right hemispheric opercular frontal cortex and caudate in adolescents--seem to have been recruited by the two groups for achieving comparable performances. A significant age effect was found for the prefrontal activation in both task, confirming the hypothesis of a dysmaturational pathogenesis for the hypofrontality in ADHD.

Comparing the German versions of the Strengths and Difficulties Questionnaire (SDQ-Deu) and the Child Behavior Checklist.

The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire that can be completed in about 5 minutes by the parents and teachers of 4-16 year olds. The scores of the English version correlate well with those of the considerably longer Child Behavior Checklist (CBCL). The present study compares the German versions of the questionnaires. Both SDQ and CBCL were completed by the parents of 273 children drawn from psychiatric clinics (N = 163) and from a community sample (N = 110). The children from the community sample also filled in the SDQ self-report and the Youth Self Report (YSR). The children from the clinic sample received an ICD-10 diagnosis if applicable. Scores from the parent and self-rated SDQ and CBCL/YSR were highly correlated and equally able to distinguish between the community and clinic samples, with the SDQ showing significantly better results regarding the total scores. They were also equally able to distinguish between disorders within the clinic sample, the only significant difference being that the SDQ was better able to differentiate between children with and without hyperactivity-inattention. The study shows that like the English originals, the SDQ-Deu and the German CBCL are equally valid for most clinical and research purposes.

Neuroimaging in hyperkinetic children and adults: an overview.

The application of brain imaging techniques to children with Attention Deficit/Hyperactivity Disorders is reviewed, stressing methodological aspects. Findings are still provisional, but suggest minor structural changes in frontal and candate areas, especially on the right side. Functional studies suggest reduced activation in these and other areas. The techniques do not yet contribute to individual diagnosis.

Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI.

OBJECTIVE: Functional magnetic resonance imaging (MRI) was used to investigate the hypothesis that attention deficit hyperactivity disorder (ADHD) is associated with a dysfunction of prefrontal brain regions during motor response inhibition and motor timing. METHOD: Generic brain activation of seven adolescent boys with ADHD was compared to that of nine comparison subjects equivalent in sex, age, and IQ while they were performing a stop task, requiring inhibition of a planned motor response, and a motor timing task, requiring timing of a motor response to a sensory cue. RESULTS: The hyperactive adolescents showed lower power of response in the right mesial prefrontal cortex during both tasks and in the right inferior prefrontal cortex and left caudate during the stop task. CONCLUSIONS: 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.

Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain.

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.

Psychosocial adversities underestimated in hyperkinetic children.

Abnormal psychosocial factors, assessed both clinically and by raters blind to clinical presentation, were examined in 21 hyperkinetic and 26 conduct disordered children. Blind raters found the frequency of psychosocial adversities to be similar in the two disorders. By contrast the clinical rater, who did know the diagnosis of patients, rated adverse psychosocial situations as much lower in hyperkinetic children than in children with conduct disorder. Logistic regression showed, particularly in the category of abnormal intrafamilial relationships (Lack of warmth in parent child relationship, Hostility or scapegoating of the child, Intrafamilial discord among adults), effects of the interaction between rater and knowledge of diagnosis. Clinical raters should be aware of abnormal psychosocial situations in hyperkinetic children and assess possible adverse effects on parents and children. Researchers should be aware of a possible bias in research interviews.

[The hyperkinetic child in ambulatory care. Therapeutic strategies for long-term care]. / Das hyperkinetische Kind in der ambulanten Behandlung. Therapiestrategien langfristig ausrichten.

Children with a hyperkinetic disorder (attention deficit, hyperactivity, impulsiveness) should be diagnosed early in order to avoid difficulties in the family and with friends, and, in particular at school, and thus to positively influence the child's development. The present article discusses the definition, course, accompanying disorders and appropriate forms of treatment. Most important for outpatient treatment is the multimodal approach, in which various forms of therapy for the children and their families are integrated. Adequate outpatient treatment facilities must be made available in order to induce the children and their families to undergo long-term treatment.

Prefrontal involvement in "temporal bridging" and timing movement.

Brain activity exclusively related to a temporal delay has rarely been investigated using modern brain imaging. In this study we exploited the temporal resolution of functional magnetic resonance imaging (fMRI) to characterise, by sinusoidal regression analysis, differential neuroactivation patterns induced in healthy subjects by two sensorimotor synchronization tasks different in their premovement delay of either 0.6 s or 5 s. The short event rate condition required rhythmic tapping, while the long event rate condition required timing of intermittent movements. Left rostral prefrontal cortex, medial frontal cortex, SMA and supramarginal gyrus demonstrated increased MR signal intensity during low frequency synchronization, suggesting that these brain regions form a distributed neural network for cognitive time management processes, such as time estimation and motor output timing. Medial frontal cortex showed a biphasic pattern of response during both synchronization conditions, presumably reflecting frequency-independent motor output related attention. As predicted, sensorimotor and visual association areas demonstrated increased MR signal intensity during high frequency synchronization.

[School refusal--a catamnestic study on the diagnostic concept ov "school phobia" and "school anxiety"]. / Schulverweigerung--Eine katamnestische Untersuchung zu dem diagnostischen Konzept von "Schulphobie" und "Schulangst".

Twenty-six patients diagnosed with school refusal were examined 2.4 years after inpatient treatment. The long-term course of patients with "school phobia" (school refusal unrelated to school) and that of patients with "school anxiety" (school refusal related to school) were compared. In addition, an attempt was made to identify variables predictive of a good outcome. The mean age of the 12 patients with "school phobia" and the 14 patients with "school anxiety" was 12.7 years at the start of inpatient treatment. The assessment of psychiatric disturbances was based on structured interviews for parents and adolescents (MEI and MADEL, 1989) and the dimensional assessment scales of functioning for children and adolescents (MSBF). The variables assessed for predictive value were taken from the patients' records during inpatient treatment and from the hospital documentation system. There was no difference in outcome between the two syndrome groups. There was a tendency to less autonomy in the patients with "school phobia". Girls had a better outcome than boys, as did patients with less absence from school prior to inpatient treatment. Overall there was no difference in the outcome of "school phobia" and "school anxiety". Therefore a new classification should be considered.

[Diagnosis of stressful life events in clinical routine practice using a (half) standardized interview]. / Die Diagnostik belastender Lebensereignisse in der klinischen Routine mittels eines (halb)standardisierten Interviews.

50 in-patients and 50 out-patients were assessed with a semi-structured interview based on the revised version of axis V (abnormal psychosocial situations) of the Multi-axial Classification Scheme. The interviewer was not acquainted with the patient's history. The information acquired during in-patient treatment was comparable to that obtained by interview, whereas during out-patient treatment, less information with lower reliability was obtained than on the interview. The study also shows that certain psychosocial factors can be identified better by interview and others by clinical assessment.

Psychiatric disturbances in children with hamartomas: a neglected somatopsychic issue. A case report.

To date, in publications on hamartomas, precocious puberty and laughing seizures have been discussed, but behavioural and cognitive abnormalities have been neglected. Therefore, we report a 14-year-old girl with a proven hamartoma, in which abnormalities of behaviour and cognition played an important role within the somatopsychic complex. In our patient, urinary incontinence during the seizures and psychiatric symptoms, such as eating disorder with obesity, school phobia, antisocial behaviour, withdrawal and cognitive problems (e.g. general slowness, deficiency of cognitive flexibility) came to the fore. The girl had not attended school regularly for almost 2 years, had stayed at home and was overtaxed psychosocially. The seizures and the urinary incontinence improved with drug treatment, but psychiatric difficulties increased and remained untreated until the girl came to a child psychiatric inpatient clinic where drug treatment and behavioural therapy were combined. During well-coordinated neurological and psychiatric treatment the laughing seizures (spontaneous, event-related, psychogenic) decreased and a considerable improvement in psychiatric and psychosocial problems was attained. Consequently, we recommend a close and timely integration of the psychiatric aspects in the treatment of children with hamartomas.