Individual classification of ADHD patients by integrating multiscale neuroimaging markers and advanced pattern recognition techniques

Accurate classification or prediction of the brain state across individual subject, i.e., healthy, or with brain disorders, is generally a more difficult task than merely finding group differences. The former must be approached with highly informative and sensitive biomarkers as well as effective pattern classification/feature selection approaches. In this paper, we propose a systematic methodology to discriminate attention deficit hyperactivity disorder (ADHD) patients from healthy controls on the individual level. Multiple neuroimaging markers that are proved to be sensitive features are identified, which include multiscale characteristics extracted from blood oxygenation level dependent (BOLD) signals, such as regional homogeneity (ReHo) and amplitude of low-frequency fluctuations. Functional connectivity derived from Pearson, partial, and spatial correlation is also utilized to reflect the abnormal patterns of functional integration, or, dysconnectivity syndromes in the brain. These neuroimaging markers are calculated on either voxel or regional level. Advanced feature selection approach is then designed, including a brain-wise association study (BWAS). Using identified features and proper feature integration, a support vector machine (SVM) classifier can achieve a cross-validated classification accuracy of 76.15% across individuals from a large dataset consisting of 141 healthy controls and 98 ADHD patients, with the sensitivity being 63.27% and the specificity being 85.11%. Our results show that the most discriminative features for classification are primarily associated with the frontal and cerebellar regions. The proposed methodology is expected to improve clinical diagnosis and evaluation of treatment for ADHD patient, and to have wider applications in diagnosis of general neuropsychiatric disorders

Working Effectively with People with Attention Deficit/ Hyperactivity Disorder

This brochure on People with Attention Deficit/Hyperactivity Disorder and the Americans with Disabilities Act (ADA) is one of a series on human resources practices and workplace accommodations for persons with disabilities edited by Susanne M. Bruyère, Ph.D., CRC, SPHR, Director, Program on Employment and Disability, School of Industrial and Labor Relations – Extension Division, Cornell University. Cornell University was funded in the early 1990’s by the U.S. Department of Education National Institute on Disability and Rehabilitation Research as a National Materials Development Project on the employment provisions (Title I) of the ADA (Grant #H133D10155). These updates, and the development of new brochures, have been funded by Cornell’s Program on Employment and Disability, the Pacific Disability and Business Technical Assistance Center, and other supporters

Neurobiology of dyslexia : A reinterpretation of the data

Theories of developmental dyslexia differ on how to best interpret the great variety of symptoms (linguistic, sensory, motor) observed in dyslexic individuals. One approach views dyslexia as a specific phonological deficit, which sometimes co-occurs with a more general sensorimotor syndrome. The present review of the neurobiology of dyslexia shows that neurobiological data are indeed consistent with this view, explaining both how a specific phonological deficit might arise, and why a sensorimotor syndrome should be significantly associated with it. This new conceptualisation of the aetiology of dyslexia may generalise to other neuro-developmental disorders, and may further explain heterogeneity within each disorder and co-morbidity between disorders

Duplications in ADHD patients harbour neurobehavioural genes that are co-expressed with genes associated with hyperactivity in the mouse

Attention deficit/hyperactivity disorder (ADHD) is a childhood onset disorder, prevalent in 5.3% of children and 1–4% of adults. ADHD is highly heritable, with a burden of large (>500 Kb) copy number variants (CNVs) identified among individuals with ADHD. However, how such CNVs exert their effects is poorly understood. We examined the genes affected by 71 large, rare, and predominantly inherited CNVs identified among 902 individuals with ADHD. We applied both mouse‐knockout functional enrichment analyses, exploiting behavioral phenotypes arising from the determined disruption of 1:1 mouse orthologues, and human brain‐specific spatio‐temporal expression data to uncover molecular pathways common among genes contributing to enriched phenotypes. Twenty‐two percent of genes duplicated in individuals with ADHD that had mouse phenotypic information were associated with abnormal learning/memory/conditioning (“l/m/c”) phenotypes. Although not observed in a second ADHD‐cohort, we identified a similar enrichment among genes duplicated by eight de novo CNVs present in eight individuals with Hyperactivity and/or Short attention span (“Hyperactivity/SAS”, the ontologically‐derived phenotypic components of ADHD). In the brain, genes duplicated in patients with ADHD and Hyperactivity/SAS and whose orthologues’ disruption yields l/m/c phenotypes in mouse (“candidate‐genes”), were co‐expressed with one another and with genes whose orthologues’ mouse models exhibit hyperactivity. Moreover, genes associated with hyperactivity in the mouse were significantly more co‐expressed with ADHD candidate‐genes than with similarly identified genes from individuals with intellectual disability. Our findings support an etiology for ADHD distinct from intellectual disability, and mechanistically related to genes associated with hyperactivity phenotypes in other mammalian species

The cerebellum and motor dysfunction in neuropsychiatric disorders

The cerebellum is densely interconnected with sensory-motor areas of the cerebral cortex, and in man, the great expansion of the association areas of cerebral cortex is also paralleled by an expansion of the lateral cerebellar hemispheres. It is therefore likely that these circuits contribute to non-motor cognitive functions, but this is still a controversial issue. One approach is to examine evidence from neuropsychiatric disorders of cerebellar involvement. In this review, we narrow this search to test whether there is evidence of motor dysfunction associated with neuropsychiatric disorders consistent with disruption of cerebellar motor function. While we do find such evidence, especially in autism, schizophrenia and dyslexia, we caution that the restricted set of motor symptoms does not suggest global cerebellar dysfunction. Moreover, these symptoms may also reflect involvement of other, extra-cerebellar circuits and detailed examination of specific sub groups of individuals within each disorder may help to relate such motor symptoms to cerebellar morphology

Dopaminergic Haplotype as a Predictor of Spatial Inattention in Children With Attention-Deficit/Hyperactivity Disorder

A distinct pattern of selective attention deficits in attention-deficit/hyperactivity disorder (ADHD) has been difficult to identify. Heterogeneity may reflect differences in underlying genetics.To document an objective deficit of selective attention in a large sample of children with and without ADHD using spatial orienting paradigms. By stratifying samples according to the gene dosage of a risk haplotype of the dopamine transporter gene (DAT1), we could determine whether genetic factors predict spatial inattention in ADHD.A case-control design was used.Children with ADHD were recruited from clinics or support groups in Ireland. Typically developing children were recruited from schools in and around Dublin, Ireland.One hundred fifteen children were recruited (ADHD = 50, control = 65). Groups were matched for age but differed in estimated intelligence.Two versions of a visual spatial orienting task in which attention was directed by valid, neutral, or invalid cues to target locations. Sudden-onset peripheral cues (exogenous) and centrally presented predictive cues (endogenous) were used.To isolate an attention deficit in ADHD, groups were first compared using analysis of variance on the spatial orienting tasks. Multiple regression was used to assess the main effect of DAT1 haplotype status (heterozygous vs homozygous) and the interaction of diagnosis and genotype on those variables that discriminated children with and without ADHD.Children with ADHD displayed deficits in reorienting attention from invalidly cued spatial locations, particularly for targets in the left visual field. DAT1 haplotype status predicted spatial reorienting deficits for left visual field targets (P = .007) but there was also a significant interaction of diagnosis and genotype (P = .02), which revealed the greatest impairment in children with ADHD homozygous for the DAT1 haplotype.Heterogeneity in selective attention in ADHD can be explained by a replicated genetic risk factor for ADHD, the 10/3 DAT1 haplotype