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      Pattern classification of response inhibition in ADHD: Toward the development of neurobiological markers for ADHD

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          Abstract

          The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) is based on subjective measures despite evidence for multisystemic structural and functional deficits. ADHD patients have consistent neurofunctional deficits in motor response inhibition. The aim of this study was to apply pattern classification to task-based functional magnetic resonance imaging (fMRI) of inhibition, to accurately predict the diagnostic status of ADHD. Thirty adolescent ADHD and thirty age-matched healthy boys underwent fMRI while performing a Stop task. fMRI data were analyzed with Gaussian process classifiers (GPC), a machine learning approach, to predict individual ADHD diagnosis based on task-based activation patterns. Traditional univariate case-control analyses were also performed to replicate previous findings in a relatively large dataset. The pattern of brain activation correctly classified up to 90% of patients and 63% of controls, achieving an overall classification accuracy of 77%. The regions of the discriminative network most predictive of controls included later developing lateral prefrontal, striatal, and temporo-parietal areas that mediate inhibition, while regions most predictive of ADHD were in earlier developing ventromedial fronto-limbic regions, which furthermore correlated with symptom severity. Univariate analysis showed reduced activation in ADHD in bilateral ventrolateral prefrontal, striatal, and temporo-parietal regions that overlapped with areas predictive of controls, suggesting the latter are dysfunctional areas in ADHD. We show that significant individual classification of ADHD patients of 77% can be achieved using whole brain pattern analysis of task-based fMRI inhibition data, suggesting that multivariate pattern recognition analyses of inhibition networks can provide objective diagnostic neuroimaging biomarkers of ADHD. Hum Brain Mapp 35:3083–3094, 2014. © 2013 Wiley Periodicals, Inc.

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          Gaussian processes formachine learning

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            Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation.

            There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test chi(1)(2) = 5,609, P < 1.0 x 10(-20)). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.
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              Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review.

              Standard univariate analysis of neuroimaging data has revealed a host of neuroanatomical and functional differences between healthy individuals and patients suffering a wide range of neurological and psychiatric disorders. Significant only at group level however these findings have had limited clinical translation, and recent attention has turned toward alternative forms of analysis, including Support-Vector-Machine (SVM). A type of machine learning, SVM allows categorisation of an individual's previously unseen data into a predefined group using a classification algorithm, developed on a training data set. In recent years, SVM has been successfully applied in the context of disease diagnosis, transition prediction and treatment prognosis, using both structural and functional neuroimaging data. Here we provide a brief overview of the method and review those studies that applied it to the investigation of Alzheimer's disease, schizophrenia, major depression, bipolar disorder, presymptomatic Huntington's disease, Parkinson's disease and autistic spectrum disorder. We conclude by discussing the main theoretical and practical challenges associated with the implementation of this method into the clinic and possible future directions. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Hum Brain Mapp
                Hum Brain Mapp
                hbm
                Human Brain Mapping
                BlackWell Publishing Ltd (Oxford, UK )
                1065-9471
                1097-0193
                July 2014
                11 October 2013
                : 35
                : 7
                : 3083-3094
                Affiliations
                [1 ]Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London De Crespigny Park, London, SE5 8AF, United Kingdom
                [2 ]Department of Neuroimaging, Institute of Psychiatry, King's College London De Crespigny Park, London, SE5 8AF, United Kingdom
                Author notes
                *Correspondence to: Katya Rubia, Department of Child & Adolescent Psychiatry, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK. E-mail: katya.rubia@ 123456kcl.ac.uk

                Contract grant sponsors: NIHR Biomedical Research Centre (BRC) for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London and Lilly Pharmaceuticals, Kids Company, NIHR BRC, King's College London Centre of Excellence in Medical Engineering; Contract grant sponsor: Well-come Trust and EPSRC; Contract grant number: Nr WT088641/Z/09/Z.

                Article
                10.1002/hbm.22386
                4190683
                24123508
                8db1c5f4-653a-4aec-b805-34304d23e685
                Copyright © 2013 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 23 May 2013
                : 19 July 2013
                : 22 July 2013
                Categories
                Research Articles

                Neurology
                adhd,biomarker,diagnosis,functional magnetic resonance imaging,gaussian process classifier,inhibition

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