title: Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).
abstract: Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs.
  
  
  METHODS
  In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.
authors.affiliation: Department of Psychiatry, University of Minnesota Twin Cities, F282/2A West, 2450 Riverside Ave, Minneapolis, MN, 55454, USA. jwozniak@umn.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Wozniak
authors.affiliation: Department of Psychiatry, University of Minnesota Twin Cities, F282/2A West, 2450 Riverside Ave, Minneapolis, MN, 55454, USA.
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Mueller
authors.affiliation: San Diego State University, San Diego, CA, 92182, USA.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Mattson
authors.affiliation: Emory University, Atlanta, GA, 30322, USA.
authors.forename: Claire D
authors.initials: CD
authors.lastname: Coles
authors.affiliation: Emory University, Atlanta, GA, 30322, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Kable
authors.affiliation: University of California, San Diego, La Jolla, CA, 92093, USA.
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Jones
authors.affiliation: Department of Psychiatry, University of Minnesota Twin Cities, F282/2A West, 2450 Riverside Ave, Minneapolis, MN, 55454, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Boys
authors.affiliation: Department of Psychiatry, University of Minnesota Twin Cities, F282/2A West, 2450 Riverside Ave, Minneapolis, MN, 55454, USA.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
authors.affiliation: San Diego State University, San Diego, CA, 92182, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Riley
authors.affiliation: Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Sowell
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D015999:Multivariate Analysis; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D009483:Neuropsychological Tests; D012146:Rest; D012189:Retrospective Studies
keywords: Brain; Fetal alcohol (FAS, FASD); Functional MRI (fMRI), resting-state, connectivity; Neuropsychology