title: Inter-hemispheric functional connectivity disruption in children with prenatal alcohol exposure.
abstract: BACKGROUND
  MRI studies, including recent diffusion tensor imaging (DTI) studies, have shown corpus callosum abnormalities in children prenatally exposed to alcohol, especially in the posterior regions. These abnormalities appear across the range of fetal alcohol spectrum disorders (FASD). Several studies have demonstrated cognitive correlates of callosal abnormalities in FASD including deficits in visual-motor skill, verbal learning, and executive functioning. The goal of this study was to determine whether inter-hemispheric structural connectivity abnormalities in FASD are associated with disrupted inter-hemispheric functional connectivity and disrupted cognition.
  
  
  METHODS
  Twenty-one children with FASD and 23 matched controls underwent a 6-minute resting-state functional MRI scan as well as anatomical imaging and DTI. Using a semi-automated method, we parsed the corpus callosum and delineated 7 inter-hemispheric white matter tracts with DTI tractography. Cortical regions of interest (ROIs) at the distal ends of these tracts were identified. Right-left correlations in resting fMRI signal were computed for these sets of ROIs, and group comparisons were made. Correlations with facial dysmorphology, cognition, and DTI measures were computed.
  
  
  RESULTS
  A significant group difference in inter-hemispheric functional connectivity was seen in a posterior set of ROIs, the para-central region. Children with FASD had functional connectivity that was 12% lower than in controls in this region. Subgroup analyses were not possible owing to small sample size, but the data suggest that there were effects across the FASD spectrum. No significant association with facial dysmorphology was found. Para-central functional connectivity was significantly correlated with DTI mean diffusivity, a measure of microstructural integrity, in posterior callosal tracts in controls but not in FASD. Significant correlations were seen between these structural and functional measures, and Wechsler perceptual reasoning ability.
  
  
  CONCLUSIONS
  Inter-hemispheric functional connectivity disturbances were observed in children with FASD relative to controls. The disruption was measured in medial parietal regions (para-central) that are connected by posterior callosal fiber projections. We have previously shown microstructural abnormalities in these same posterior callosal regions, and the current study suggests a possible relationship between the two. These measures have clinical relevance as they are associated with cognitive functioning.
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, 55454, USA. jwozniak@umn.edu
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Wozniak
authors.forename: Bryon A
authors.initials: BA
authors.lastname: Mueller
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Muetzel
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bell
authors.forename: Heather L
authors.initials: HL
authors.lastname: Hoecker
authors.forename: Miranda L
authors.initials: ML
authors.lastname: Nelson
authors.forename: Pi-Nian
authors.initials: PN
authors.lastname: Chang
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D002648:Child; D003337:Corpus Callosum / Q000503:physiopathology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis / Q000503:physiopathology*