title: White matter microstructure and atypical visual orienting in 7-month-olds at risk for autism.
abstract: OBJECTIVE The authors sought to determine whether specific patterns of oculomotor functioning and visual orienting characterize 7-month-old infants who later meet criteria for an autism spectrum disorder (ASD) and to identify the neural correlates of these behaviors. METHOD Data were collected from 97 infants, of whom 16 were high-familial-risk infants later classified as having an ASD, 40 were high-familial-risk infants who did not later meet ASD criteria (high-risk negative), and 41 were low-risk infants. All infants underwent an eye-tracking task at a mean age of 7 months and a clinical assessment at a mean age of 25 months. Diffusion-weighted imaging data were acquired for 84 of the infants at 7 months. Primary outcome measures included average saccadic reaction time in a visually guided saccade procedure and radial diffusivity (an index of white matter organization) in fiber tracts that included corticospinal pathways and the splenium and genu of the corpus callosum. RESULTS Visual orienting latencies were longer in 7-month-old infants who expressed ASD symptoms at 25 months compared with both high-risk negative infants and low-risk infants. Visual orienting latencies were uniquely associated with the microstructural organization of the splenium of the corpus callosum in low-risk infants, but this association was not apparent in infants later classified as having an ASD. CONCLUSIONS Flexibly and efficiently orienting to salient information in the environment is critical for subsequent cognitive and social-cognitive development. Atypical visual orienting may represent an early prodromal feature of an ASD, and abnormal functional specialization of posterior cortical circuits directly informs a novel model of ASD pathogenesis.
authors.affiliation: Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill, USA. jelison@caltech.edu
authors.forename: Jed T
authors.initials: JT
authors.lastname: Elison
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Paterson
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Wolff
authors.forename: J Steven
authors.initials: JS
authors.lastname: Reznick
authors.forename: Noah J
authors.initials: NJ
authors.lastname: Sasson
authors.forename: Hongbin
authors.initials: H
authors.lastname: Gu
authors.forename: Kelly N
authors.initials: KN
authors.lastname: Botteron
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Dager
authors.forename: Annette M
authors.initials: AM
authors.lastname: Estes
authors.forename: Alan C
authors.initials: AC
authors.lastname: Evans
authors.forename: Guido
authors.initials: G
authors.lastname: Gerig
authors.forename: Heather C
authors.initials: HC
authors.lastname: Hazlett
authors.forename: Robert T
authors.initials: RT
authors.lastname: Schultz
authors.forename: Martin
authors.initials: M
authors.lastname: Styner
authors.forename: Lonnie
authors.initials: L
authors.lastname: Zwaigenbaum
authors.forename: Joseph
authors.initials: J
authors.lastname: Piven
mesh_terms: D001288:Attention / Q000502:physiology*; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D003337:Corpus Callosum / Q000473:pathology / Q000503:physiopathology; D038524:Diffusion Magnetic Resonance Imaging; D056348:Emotional Intelligence / Q000235:genetics / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007223:Infant; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D009949:Orientation / Q000502:physiology*; D011712:Pyramidal Tracts / Q000473:pathology / Q000503:physiopathology; D011930:Reaction Time / Q000235:genetics / Q000502:physiology; D012016:Reference Values; D012154:Reticular Formation / Q000473:pathology / Q000503:physiopathology; D012438:Saccades / Q000235:genetics / Q000502:physiology*; D013477:Superior Colliculi / Q000473:pathology / Q000503:physiopathology; D014795:Visual Pathways / Q000473:pathology / Q000503:physiopathology