title: Characterising resting-state functional connectivity in a large sample of adults with ADHD.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated small samples. We therefore investigated aberrant functional connectivity in a large sample of adult patients with childhood-onset ADHD, using a data-driven, whole-brain approach. Adults with a clinical ADHD diagnosis (N=99) and healthy, adult comparison subjects (N=113) underwent a 9-minute resting-state fMRI session in a 1.5T MRI scanner. After elaborate preprocessing including a thorough head-motion correction procedure, group independent component analysis (ICA) was applied from which we identified six networks of interest: cerebellum, executive control, left and right frontoparietal and two default-mode networks. Participant-level network maps were obtained using dual-regression and tested for differences between patients with ADHD and controls using permutation testing. Patients showed significantly stronger connectivity in the anterior cingulate gyrus of the executive control network. Trends were also observed for stronger connectivity in the cerebellum network in ADHD patients compared to controls. However, there was considerable overlap in connectivity values between patients and controls, leading to relatively low effect sizes despite the large sample size. These effect sizes were slightly larger when testing for correlations between hyperactivity/impulsivity symptoms and connectivity strength in the executive control and cerebellum networks. This study provides important insights for studies on the neurobiology of adult ADHD; it shows that resting-state functional connectivity differences between adult patients and controls exist, but have smaller effect sizes than existing literature suggested.
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands; Radboud University Medical Center, Department of Human Genetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: jeanettemostert@gmail.com.
authors.forename: Jeanette C
authors.initials: JC
authors.lastname: Mostert
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands; Radboud University Medical Center, Department of Human Genetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: e.shumskaya@donders.ru.nl.
authors.forename: Elena
authors.initials: E
authors.lastname: Shumskaya
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands. Electronic address: m.mennes@donders.ru.nl.
authors.forename: Maarten
authors.initials: M
authors.lastname: Mennes
authors.affiliation: Radboud University Medical Center, Department of Human Genetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: marten.onnink@radboudumc.nl.
authors.forename: A Marten H
authors.initials: AM
authors.lastname: Onnink
authors.affiliation: Radboud University Medical Center, Department of Human Genetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: martine.hoogman@radboudumc.nl.
authors.forename: Martine
authors.initials: M
authors.lastname: Hoogman
authors.affiliation: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: cees.kan@radboudumc.nl.
authors.forename: Cornelis C
authors.initials: CC
authors.lastname: Kan
authors.affiliation: Radboud University Medical Center, Department of Human Genetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: alejandro.ariasvasquez@radboudumc.nl.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Arias Vasquez
authors.affiliation: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: jan.buitelaar@radboudumc.nl.
authors.forename: Jan
authors.initials: J
authors.lastname: Buitelaar
authors.affiliation: Radboud University Medical Center, Department of Human Genetics, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Cognitive Neuroscience, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: barbara.franke@radboudumc.nl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands. Electronic address: d.norris@donders.ru.nl.
authors.forename: David G
authors.initials: DG
authors.lastname: Norris
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D001921:Brain / Q000000981:diagnostic imaging*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012146:Rest; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Adult ADHD; Cerebellum; Executive control network; Independent component analysis; Resting-state functional connectivity
references.citation: Neuroimage. 2009 Oct 15;48(1):63-72
references.pmid: 19573611
references.citation: J Psychiatr Res. 2010 Jul;44(10):629-39
references.pmid: 20060129
references.citation: J Cogn Neurosci. 2011 Dec;23(12):4022-37
references.pmid: 21671731
references.citation: Neuroimage. 2009 Jan 1;44(1):83-98
references.pmid: 18501637
references.citation: Neuroimage. 2002 Oct;17(2):825-41
references.pmid: 12377157
references.citation: JAMA Psychiatry. 2013 Aug;70(8):869-79
references.pmid: 23803651
references.citation: Neuroimage. 2015 May 15;112:278-87
references.pmid: 25770990
references.citation: Psychol Med. 2005 Jun;35(6):817-27
references.pmid: 15997602
references.citation: Front Syst Neurosci. 2013 Feb 04;6:80
references.pmid: 23382713
references.citation: Neuroimage. 2002 Oct;17(2):967-76
references.pmid: 12377170
references.citation: Neuroimage. 2013 Nov 1;81:213-21
references.pmid: 23684862
references.citation: Neurosci Lett. 2006 May 29;400(1-2):39-43
references.pmid: 16510242
references.citation: Eur Neuropsychopharmacol. 2014 Mar;24(3):397-409
references.pmid: 24345721
references.citation: Am J Psychiatry. 1991 May;148(5):564-77
references.pmid: 2018156
references.citation: Nat Rev Neurosci. 2013 May;14(5):365-76
references.pmid: 23571845
references.citation: Cortex. 2012 Feb;48(2):194-215
references.pmid: 21575934
references.citation: Br J Psychiatry. 2009 Mar;194(3):204-11
references.pmid: 19252145
references.citation: Eur J Radiol. 2013 Sep;82(9):1552-7
references.pmid: 23684384
references.citation: Biol Psychiatry. 2005 Jun 1;57(11):1224-30
references.pmid: 15949992
references.citation: Prog Neurobiol. 2013 Sep;108:44-79
references.pmid: 23856628
references.citation: J Abnorm Child Psychol. 2009 May;37(4):551-64
references.pmid: 19016322
references.citation: Neuropsychopharmacology. 2010 Jan;35(1):278-300
references.pmid: 19759528
references.citation: Am J Psychiatry. 2010 Jan;167(1):86-94
references.pmid: 19884224
references.citation: Biol Psychiatry. 2012 Mar 1;71(5):434-42
references.pmid: 21974788
references.citation: Front Syst Neurosci. 2010 Apr 06;4:8
references.pmid: 20407579
references.citation: Neurosci Biobehav Rev. 2007;31(7):977-86
references.pmid: 17445893
references.citation: Neuroimage. 2012 Jan 2;59(1):431-8
references.pmid: 21810475
references.citation: Psychol Med. 2006 Feb;36(2):159-65
references.pmid: 16420712
references.citation: Neuroimage. 2015 May 15;112:267-77
references.pmid: 25770991
references.citation: J Child Psychol Psychiatry. 2011 Sep;52(9):954-63
references.pmid: 21434915
references.citation: Biol Psychiatry. 2010 Dec 15;68(12):1084-91
references.pmid: 20728873
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13848-53
references.pmid: 16945915
references.citation: JAMA Psychiatry. 2013 Dec;70(12):1329-37
references.pmid: 24132732
references.citation: PLoS One. 2012;7(9):e45671
references.pmid: 23049834
references.citation: Neuroimage. 2009 Feb 1;44(3):893-905
references.pmid: 18976716
references.citation: Hum Brain Mapp. 2014 Apr;35(4):1261-72
references.pmid: 23417778
references.citation: Med Image Anal. 2001 Jun;5(2):143-56
references.pmid: 11516708
references.citation: Neuropsychopharmacology. 2010 Feb;35(3):656-64
references.pmid: 19890261
references.citation: Biol Psychiatry. 2004 Apr 1;55(7):692-700
references.pmid: 15038997
references.citation: Neuropsychology. 2004 Jul;18(3):485-503
references.pmid: 15291727
references.citation: Neuropsychol Rev. 2014 Mar;24(1):3-15
references.pmid: 24496902
references.citation: Biol Psychiatry. 2011 Jun 15;69(12):1168-77
references.pmid: 21546000
references.citation: Drug Alcohol Depend. 2012 Oct 1;125(3):252-9
references.pmid: 22459914
references.citation: Front Syst Neurosci. 2010 Sep 20;4:null
references.pmid: 20941370
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5
references.pmid: 19620724
references.citation: J Neurosci. 2007 Feb 28;27(9):2349-56
references.pmid: 17329432
references.citation: Eur Neuropsychopharmacol. 2013 Jun;23(6):469-78
references.pmid: 22749356
references.citation: Biol Psychiatry. 2011 Jun 15;69(12):1160-7
references.pmid: 21489409
references.citation: Hum Brain Mapp. 2010 Jun;31(6):904-16
references.pmid: 20496381
references.citation: Trends Cogn Sci. 2012 Jan;16(1):17-26
references.pmid: 22169776
references.citation: Am J Psychiatry. 2010 Jul;167(7):748-51
references.pmid: 20595427
references.citation: Psychol Med. 2014 Jul;44(9):1989-2001
references.pmid: 24176104
references.citation: J Neurophysiol. 2011 Sep;106(3):1125-65
references.pmid: 21653723
references.citation: Neuropharmacology. 2009 Dec;57(7-8):640-52
references.pmid: 19715709
references.citation: J Neurosci Methods. 2008 Mar 30;169(1):249-54
references.pmid: 18190970
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
references.pmid: 11209064
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7209-14
references.pmid: 19357304
references.citation: Cortex. 2015 Dec;73:62-72
references.pmid: 26363140
references.citation: Biol Psychiatry. 2008 Feb 1;63(3):332-7
references.pmid: 17888409
references.citation: Dev Neurosci. 2009;31(1-2):36-49
references.pmid: 19372685
references.citation: Am J Psychiatry. 2012 Oct;169(10):1038-55
references.pmid: 22983386
references.citation: Neuroreport. 2006 Jul 17;17(10):1033-6
references.pmid: 16791098
references.citation: Philos Trans R Soc Lond B Biol Sci. 2005 May 29;360(1457):1001-13
references.pmid: 16087444