Daniel von Rhein1,2, Marianne Oldehinkel1,2, Christian F Beckmann1,2,3, Jaap Oosterlaan4, Dirk Heslenfeld4, Catharina A Hartman5, Pieter J Hoekstra5, Barbara Franke6,7, Roshan Cools2,7, Jan K Buitelaar1,2,8, Maarten Mennes2. 1. Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, The Netherlands. 2. Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands. 3. Centre for Functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK. 4. Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, The Netherlands. 5. Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 6. Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands. 7. Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands. 8. Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.
Abstract
BACKGROUND: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whether ADHD-related alterations are limited to local, intrastriatal functional connections. METHODS: We included a cohort of adolescents with ADHD (N = 181) and healthy controls (N = 140) and assessed functional connectivity of nucleus accumbens, caudate nucleus, anterior putamen, and posterior putamen. To assess global cortico-striatal functional architecture we computed whole-brain functional connectivity by including all regions of interest in one multivariate analysis. We assessed local striatal functional connectivity using partial correlations between the time series of the striatal regions. RESULTS: Diagnostic status did not influence global cortico-striatal functional architecture. However, compared to controls, participants with ADHD exhibited significantly increased local functional connectivity between anterior and posterior putamen (p = .0003; ADHD: z = .30, controls: z = .24). Results were not affected by medication use or comorbid oppositional defiant disorder and conduct disorder. CONCLUSIONS: Our results do not support hypotheses that ADHD is associated with alterations in cortico-striatal networks, but suggest changes in local striatal functional connectivity. We interpret our findings as aberrant development of local functional connectivity of the putamen, potentially leading to decreased functional segregation between anterior and posterior putamen in ADHD.
BACKGROUND: Task-based and resting-state functional Magnetic Resonance Imaging (fMRI) studies report attention-deficit/hyperactivity disorder (ADHD)-related alterations in brain regions implicated in cortico-striatal networks. We assessed whether ADHD is associated with changes in the brain's global cortico-striatal functional architecture, or whether ADHD-related alterations are limited to local, intrastriatal functional connections. METHODS: We included a cohort of adolescents with ADHD (N = 181) and healthy controls (N = 140) and assessed functional connectivity of nucleus accumbens, caudate nucleus, anterior putamen, and posterior putamen. To assess global cortico-striatal functional architecture we computed whole-brain functional connectivity by including all regions of interest in one multivariate analysis. We assessed local striatal functional connectivity using partial correlations between the time series of the striatal regions. RESULTS: Diagnostic status did not influence global cortico-striatal functional architecture. However, compared to controls, participants with ADHD exhibited significantly increased local functional connectivity between anterior and posterior putamen (p = .0003; ADHD: z = .30, controls: z = .24). Results were not affected by medication use or comorbid oppositional defiant disorder and conduct disorder. CONCLUSIONS: Our results do not support hypotheses that ADHD is associated with alterations in cortico-striatal networks, but suggest changes in local striatal functional connectivity. We interpret our findings as aberrant development of local functional connectivity of the putamen, potentially leading to decreased functional segregation between anterior and posterior putamen in ADHD.
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