title: Quantifying patterns of brain activity: Distinguishing unaffected siblings from participants with ADHD and healthy individuals.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent and heritable psychiatric disorders. While previous studies have focussed on mapping focal or connectivity differences at the group level, the present study employed pattern recognition to quantify group separation between unaffected siblings, participants with ADHD, and healthy controls on the basis of spatially distributed brain activations. This was achieved using an fMRI-adapted version of the Stop-Signal Task in a sample of 103 unaffected siblings, 184 participants with ADHD, and 128 healthy controls. We used activation maps derived from three task regressors as features in our analyses employing a Gaussian process classifier. We showed that unaffected siblings could be distinguished from participants with ADHD (area under the receiver operating characteristic curve (AUC) = 0.65, p = 0.002, 95% Modified Wald CI: 0.59-0.71 AUC) and healthy controls (AUC = 0.59, p = 0.030, 95% Modified Wald CI: 0.52-0.66 AUC), although the latter did not survive correction for multiple comparisons. Further, participants with ADHD could be distinguished from healthy controls (AUC = 0.64, p = 0.001, 95% Modified Wald CI: 0.58-0.70 AUC). Altogether the present results characterise a pattern of frontolateral, superior temporal and inferior parietal expansion that is associated with risk for ADHD. Unaffected siblings show differences primarily in frontolateral regions. This provides evidence for a neural profile shared between participants with ADHD and their healthy siblings.
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wolfers
authors.affiliation: Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: van Rooij
authors.affiliation: Clinical Neuropsychology section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Oosterlaan
authors.affiliation: Clinical Neuropsychology section, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Heslenfeld
authors.affiliation: Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Catharina A
authors.initials: CA
authors.lastname: Hartman
authors.affiliation: Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Hoekstra
authors.affiliation: Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands; Centre for Functional MRI of the Brain (FMRIB), University of Oxford, Oxford, United Kingdom.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Beckmann
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, The Netherlands; Karakter Child and Adolescent Psychiatry University Centre, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Buitelaar
authors.affiliation: Donders Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands; Department of Neuroimaging, Institute of Psychiatry, King's College London, London, United Kingdom.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Marquand
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods*; D002648:Child; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D010363:Pattern Recognition, Automated; D012680:Sensitivity and Specificity; D035781:Siblings; D055815:Young Adult
keywords: Attention-deficit/hyperactivity disorder; Gaussian process classification; Pattern recognition; Response inhibition; Unaffected siblings; fMRI