title: Disrupted functional connectivity of cerebellar default network areas in attention-deficit/hyperactivity disorder.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD.
authors.affiliation: Deparment of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Aaron
authors.initials: A
authors.lastname: Kucyi
authors.affiliation: Deparment of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hove
authors.affiliation: Deparment of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Biederman
authors.affiliation: Department of Radiology, Athinoula a. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, Massachusetts.|Department of Psychology, Harvard University, Center for Brain Science, Cambridge, Massachusetts.
authors.forename: Koene R A
authors.initials: KR
authors.lastname: Van Dijk
authors.affiliation: Deparment of Psychiatry, Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry, Massachusetts General Hospital, Charlestown, Massachusetts.
authors.forename: Eve M
authors.initials: EM
authors.lastname: Valera
mesh_terms: D001288:Attention; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology*; D001931:Brain Mapping; D002531:Cerebellum / Q000503:physiopathology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D012146:Rest; D055815:Young Adult
keywords: attention-deficit/hyperactivity disorder; cerebellum; default mode network; functional connectivity; inattention; resting state