Intra- and inter-hemispheric structural connectome in agenesis of the corpus callosum

Minghui Shi, Lorena G A Freitas, Megan M Spencer-Smith, Valeria Kebets, Vicki Anderson, Alissandra McIlroy, Amanda G Wood, Richard J Leventer, Dimitri Van De Ville, Vanessa Siffredi

Research output: Contribution to journalArticlepeer-review


Agenesis of the corpus callosum (AgCC) is a congenital brain malformation characterized by the complete or partial failure to develop the corpus callosum. Despite missing the largest white matter bundle connecting the left and right hemispheres of the brain, studies have shown preserved inter-hemispheric communication in individuals with AgCC. It is likely that plasticity provides mechanisms for the brain to adjust in the context of AgCC, as the malformation disrupts programmed developmental brain processes very early on. A proposed candidate for neuroplastic response in individuals with AgCC is strengthening of intra-hemispheric structural connections. In the present study, we explore this hypothesis using a graph-based approach of the structural connectome, which enables intra- and inter-hemispheric analyses at multiple resolutions and quantification of structural characteristics through graph metrics. Structural graph metrics of 19 children with AgCC (13 with complete, 6 with partial AgCC) were compared to those of 29 typically developing controls (TDC). Associations between structural graph metrics and a wide range of neurobehavioral outcomes were examined using a multivariate data-driven approach (Partial Least Squares Correlation, PLSC). Our results provide new evidence suggesting structural strengthening of intra-hemispheric pathways as a neuroplastic response in the acallosal brain, and highlight regional variability in structural connectivity in children with AgCC compared to TDC. There was little evidence that structural graph properties in children with AgCC were associated with neurobehavioral outcomes. To our knowledge, this is the first report leveraging graph theory tools to explicitly characterize whole-brain intra- and inter-hemispheric structural connectivity in AgCC, opening avenues for future research on neuroplastic responses in AgCC.

Original languageEnglish
Article number102709
JournalNeuroImage: Clinical
Early online date5 Jun 2021
Publication statusPublished - 2021

Bibliographical note

© 2021 The Authors. This is an open access article under the CC BY-NC-ND license

Funding: The Boninchi Foundation from the University of Geneva; the Victorian Government’s Operational Infrastructure Support Program; the Murdoch Children’s Research Institute. European Research Council Consolidator Fellowship (682734 to A.W.); a Melbourne Children’s Clinician Scientist Fellowship (to R.L.); the Australian National Health and Medical Research Council Senior Practitioner Fellowship (to V.A.).


  • Agenesis of the corpus callosum
  • Brain plasticity
  • Graph metrics
  • Structural connectome


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