title: Reduced Functional Connectivity of Default Mode and Set-Maintenance Networks in Ornithine Transcarbamylase Deficiency.
abstract: OBJECTIVE
  Ornithine transcarbamylase deficiency (OTCD) is an X-chromosome linked urea cycle disorder (UCD) that causes hyperammonemic episodes leading to white matter injury and impairments in executive functioning, working memory, and motor planning. This study aims to investigate differences in functional connectivity of two resting-state networks--default mode and set-maintenance--between OTCD patients and healthy controls.
  
  
  METHODS
  Sixteen patients with partial OTCD and twenty-two control participants underwent a resting-state scan using 3T fMRI. Combining independent component analysis (ICA) and region-of-interest (ROI) analyses, we identified the nodes that comprised each network in each group, and assessed internodal connectivity.
  
  
  RESULTS
  Group comparisons revealed reduced functional connectivity in the default mode network (DMN) of OTCD patients, particularly between the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) node and bilateral inferior parietal lobule (IPL), as well as between the ACC/mPFC node and the posterior cingulate cortex (PCC) node. Patients also showed reduced connectivity in the set-maintenance network, especially between right anterior insula/frontal operculum (aI/fO) node and bilateral superior frontal gyrus (SFG), as well as between the right aI/fO and ACC and between the ACC and right SFG.
  
  
  CONCLUSIONS
  Internodal functional connectivity in the DMN and set-maintenance network is reduced in patients with partial OTCD compared to controls, most likely due to hyperammonemia-related white matter damage. Because several of the affected areas are involved in executive functioning, it is postulated that this reduced connectivity is an underlying cause of the deficits OTCD patients display in this cognitive domain.
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington, DC, United States of America; Department of Neurology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Ileana
authors.initials: I
authors.lastname: Pacheco-Colón
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington, DC, United States of America; Department of Neurology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Washington
authors.affiliation: Department of Neurogenetics, Children's National Health System, Washington, DC, United States of America; George Washington University of the Health Sciences, Washington, DC, United States of America.
authors.forename: Courtney
authors.initials: C
authors.lastname: Sprouse
authors.affiliation: Department of Neurogenetics, Children's National Health System, Washington, DC, United States of America.
authors.forename: Guy
authors.initials: G
authors.lastname: Helman
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington, DC, United States of America; Department of Neurogenetics, Children's National Health System, Washington, DC, United States of America; George Washington University of the Health Sciences, Washington, DC, United States of America; Medical Genetics Branch, NHGRI, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Gropman
authors.affiliation: Center for Functional and Molecular Imaging, Georgetown University, Washington, DC, United States of America; Department of Neurology, Georgetown University Medical Center, Washington, DC, United States of America.
authors.forename: John W
authors.initials: JW
authors.lastname: VanMeter
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D056344:Executive Function; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term; D008875:Middle Aged; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology; D055815:Young Adult