title: Abnormal auditory and language pathways in children with 16p11.2 deletion.
abstract: Copy number variations at chromosome 16p11.2 contribute to neurodevelopmental disorders, including autism spectrum disorder (ASD). This study seeks to improve our understanding of the biological basis of behavioral phenotypes common in ASD, in particular the prominent and prevalent disruption of spoken language seen in children with the 16p11.2 BP4-BP5 deletion. We examined the auditory and language white matter pathways with diffusion MRI in a cohort of 36 pediatric deletion carriers and 45 age-matched controls. Diffusion MR tractography of the auditory radiations and the arcuate fasciculus was performed to generate tract specific measures of white matter microstructure. In both tracts, deletion carriers exhibited significantly higher diffusivity than that of controls. Cross-sectional diffusion parameters in these tracts changed with age with no group difference in the rate of maturation. Within deletion carriers, the left-hemisphere arcuate fasciculus mean and radial diffusivities were significantly negatively correlated with clinical language ability, but not non-verbal cognitive ability. Diffusion metrics in the right-hemisphere arcuate fasciculus were not predictive of language ability. These results provide insight into the link between the 16p11.2 deletion, abnormal auditory and language pathway structures, and the specific behavioral deficits that may contribute to neurodevelopmental disorders such as ASD.
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA ; Department of Radiology, Perelman School of Medicine University of Pennsylvania, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Berman
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Darina
authors.initials: D
authors.lastname: Chudnovskaya
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Blaskey
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Kuschner
authors.affiliation: Department of Radiology, University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA.
authors.forename: Pratik
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: Department of Psychology, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Buckner
authors.affiliation: Department of Radiology, University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA.
authors.forename: Srikantan
authors.initials: S
authors.lastname: Nagarajan
authors.affiliation: Department of Pediatric, Columbia University Medical Center, New York, NY 10032, USA ; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Chung
authors.affiliation: Simons Foundation, New York, NY 10010, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Spiro
authors.affiliation: Department of Neurology, University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA.
authors.forename: Elliott H
authors.initials: EH
authors.lastname: Sherr
authors.affiliation: Department of Radiology, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA ; Department of Radiology, Perelman School of Medicine University of Pennsylvania, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.
authors.forename: Timothy P L
authors.initials: TP
authors.lastname: Roberts
mesh_terms: D000293:Adolescent; D001306:Auditory Pathways / Q000473:pathology*; D001321:Autistic Disorder / Q000473:pathology*; D001921:Brain / Q000473:pathology; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000473:pathology*; D002885:Chromosomes, Human, Pair 16; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D006801:Humans; D008607:Intellectual Disability / Q000473:pathology*; D007802:Language; D008297:Male; D066127:White Matter / Q000473:pathology
keywords: 16p11.2 deletion; AD, axial diffusivity; ASD, autism spectrum disorder; Arcuate fasciculus; Auditory system; Autism; CELF, clinical evaluation of language fundamentals; CNV, copy number variation; DTI, diffusion tensor imaging; Diffusion MR; FA, fractional anisotropy; GFA, generalized fractional anisotropy; HARDI, high angular resolution diffusion imaging; Language; MD, mean diffusivity; RD, radial diffusivity