PMID- 28861338 OWN - NLM STAT- MEDLINE DCOM- 20180510 LR - 20231112 IS - 2213-1582 (Electronic) IS - 2213-1582 (Linking) VI - 16 DP - 2017 TI - Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD. PG - 369-382 LID - 10.1016/j.nicl.2017.03.008 [doi] AB - Insufficient suppression and connectivity of the default mode network (DMN) is a potential mediator of cognitive dysfunctions across various disorders, including attention deficit/hyperactivity disorder (ADHD). However, it remains unclear if alterations in sustained DMN suppression, variability and connectivity during prolonged cognitive engagement are implicated in adult ADHD pathophysiology, and to which degree methylphenidate (MPH) remediates any DMN abnormalities. This randomized, double-blinded, placebo-controlled, cross-over clinical trial of MPH (clinicaltrials.gov/ct2/show/NCT01831622) explored large-scale brain network dynamics in 20 adults with ADHD on and off MPH, compared to 27 healthy controls, while performing a reward based decision-making task. DMN task-related activation, variability, and connectivity were estimated and compared between groups and conditions using independent component analysis, dual regression, and Bayesian linear mixed models. The results show that the DMN exhibited more variable activation patterns in unmedicated patients compared to healthy controls. Group differences in functional connectivity both between and within functional networks were evident. Further, functional connectivity between and within attention and DMN networks was sensitive both to task performance and case-control status. MPH altered within-network connectivity of the DMN and visual networks, but not between-network connectivity or temporal variability. This study thus provides novel fMRI evidence of reduced sustained DMN suppression in adults with ADHD during value-based decision-making, a pattern that was not alleviated by MPH. We infer from multiple analytical approaches further support to the default mode interference hypothesis, in that higher DMN activation variability is evident in adult ADHD and associated with lower task performance. FAU - Mowinckel, Athanasia M AU - Mowinckel AM AD - Department of Psychology, University of Oslo, 0373 Oslo, Norway. FAU - Alnaes, Dag AU - Alnaes D AD - Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Norway. FAU - Pedersen, Mads L AU - Pedersen ML AD - Department of Psychology, University of Oslo, 0373 Oslo, Norway. AD - Intervention Center, Oslo University Hospital, Rikshospitalet, 0372 Oslo, Norway. FAU - Ziegler, Sigurd AU - Ziegler S AD - Department of Psychology, University of Oslo, 0373 Oslo, Norway. AD - Institute of Clinical Medicine, University of Oslo, P.O. box 1171, Blindern, 0318 Oslo, Norway. FAU - Fredriksen, Mats AU - Fredriksen M AD - Division of Mental Health and Addiction, Vestfold Hospital Trust, 3103 Tonsberg, Norway. FAU - Kaufmann, Tobias AU - Kaufmann T AD - Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Norway. FAU - Sonuga-Barke, Edmund AU - Sonuga-Barke E AD - Institute of Psychiatry, Psychology and Neuroscience Kings College London, United Kingdom. FAU - Endestad, Tor AU - Endestad T AD - Department of Psychology, University of Oslo, 0373 Oslo, Norway. FAU - Westlye, Lars T AU - Westlye LT AD - Department of Psychology, University of Oslo, 0373 Oslo, Norway. AD - Norwegian Centre for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Norway. FAU - Biele, Guido AU - Biele G AD - Department of Psychology, University of Oslo, 0373 Oslo, Norway. AD - Norwegian Institute of Public Health, Division of Mental Health, 0403 Oslo, Norway. LA - eng SI - ClinicalTrials.gov/NCT01831622 PT - Journal Article PT - Randomized Controlled Trial DEP - 20170330 PL - Netherlands TA - Neuroimage Clin JT - NeuroImage. Clinical JID - 101597070 RN - 0 (Central Nervous System Stimulants) RN - 207ZZ9QZ49 (Methylphenidate) SB - IM MH - Adult MH - Attention Deficit Disorder with Hyperactivity/*drug therapy/*physiopathology MH - Central Nervous System Stimulants/administration & dosage/*pharmacology MH - Connectome/*methods MH - Cross-Over Studies MH - Decision Making/drug effects/*physiology MH - Double-Blind Method MH - Female MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Methylphenidate/administration & dosage/*pharmacology MH - Nerve Net/diagnostic imaging/*drug effects/*physiopathology MH - Psychomotor Performance/drug effects/*physiology MH - *Reward PMC - PMC5568884 OTO - NOTNLM OT - Adult ADHD OT - DMN OT - Decision-making OT - Dopamine OT - Functional networks OT - Reward OT - fMRI EDAT- 2017/09/02 06:00 MHDA- 2018/05/11 06:00 PMCR- 2017/03/30 CRDT- 2017/09/02 06:00 PHST- 2016/08/31 00:00 [received] PHST- 2017/02/01 00:00 [revised] PHST- 2017/03/23 00:00 [accepted] PHST- 2017/09/02 06:00 [entrez] PHST- 2017/09/02 06:00 [pubmed] PHST- 2018/05/11 06:00 [medline] PHST- 2017/03/30 00:00 [pmc-release] AID - S2213-1582(17)30068-2 [pii] AID - 10.1016/j.nicl.2017.03.008 [doi] PST - epublish SO - Neuroimage Clin. 2017 Mar 30;16:369-382. doi: 10.1016/j.nicl.2017.03.008. eCollection 2017.