Altered structural brain connectivity involving the dorsal and ventral language pathways in 16p11.2 deletion syndrome

  • Banu Ahtam
  • Naira Link
  • Erikson Hoff
  • P. Ellen Grant
  • Kiho Im
Original Research


Copy number variants at the chromosomal locus 16p11.2 contribute to neurodevelopmental disorders such as autism spectrum disorders, epilepsy, schizophrenia, and language and articulation disorders. Here, we provide detailed findings on the disrupted structural brain connectivity in 16p11.2 deletion syndrome (patients: N = 21, age range: 8–16 years; typically developing (TD) controls: 18, 9–16 years) using structural and diffusion MRI. We performed global short-, middle-, long-range, and interhemispheric connectivity analysis in the whole brain using gyral topology-based cortical parcellation. Using region of interest analysis, we studied bilateral dorsal (3 segments of arcuate fasciculus (AF)) and ventral (inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF)) language pathways. Our results showed significantly increased axial (AD) and radial (RD) diffusivities in bilateral anterior AF, decreased volume for left long AF, increased mean diffusivity (MD) and RD for right long AF, and increased AD for bilateral UF in the 16p11.2 deletion group in the absence of significant abnormalities in the whole-brain gyral and interhemispheric connectivity. The selective involvement of the language networks may aid in understanding effects of altered white matter connectivity on neurodevelopmental outcomes in 16p11.2 deletion.


16p11.2 deletion Brain networks Diffusion tensor imaging Language pathways Autism 



This work is submitted on behalf of the Simons Variation in Individuals Project (Simons VIP) investigators. We are grateful to all off the families at the participating Simons Variation in Individuals Project (Simons VIP) sites, as well as the investigators in the Simons VIP Consortium (Simons VIP Consortium, 2012). We are thankful to be given access to the phenotypic data on SFARI Base. We would also like to acknowledge Marie Drottar and Ashley Curran for their assistance.


This study was funded by R01HD079484, R01EB014947, R01HD076258, R01HD065762, and R21HD083956.

Compliance with ethical standards

Conflict of interest

Authors Banu Ahtam, Naira Link, Erikson Hoff, P. Ellen Grant, and Kiho Im declare that they have no conflict of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

11682_2018_9859_MOESM1_ESM.docx (179 kb)
Supplementary Table 1 (DOCX 179 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Fetal-Neonatal Neuroimaging & Developmental Science Center, Boston Children’s HospitalHarvard Medical SchoolBostonUSA
  2. 2.Division of Newborn Medicine, Department of Medicine, Boston Children’s HospitalHarvard Medical SchoolBostonUSA
  3. 3.Division of Neuroradiology, Department of Radiology, Boston Children’s HospitalHarvard Medical SchoolBostonUSA

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