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On the role of the corpus callosum in interhemispheric functional connectivity in humans

  1. Eric C. Leuthardta,d,e,f,g,h
  1. aDepartment of Neurological Surgery, Washington University in St. Louis, St. Louis, MO 63110;
  2. bMallinckrodt Institute Radiology, Washington University in St. Louis, St. Louis, MO 63110;
  3. cNeurology, Washington University in St. Louis, St. Louis, MO 63110;
  4. dBiomedical Engineering, Washington University in St. Louis, St. Louis, MO 63110;
  5. eNeuroscience, Washington University in St. Louis, St. Louis, MO 63110;
  6. fMechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63110;
  7. gCenter for Innovation in Neuroscience and Technology, Washington University in St. Louis, St. Louis, MO 63110;
  8. hBrain Laser Center, Washington University in St. Louis, St. Louis, MO 63110
  1. Edited by Michel Thiebaut de Schotten, Institut du Cerveau et de la Moelle épinière, Paris, France, and accepted by Editorial Board Member Marlene Behrmann November 7, 2017 (received for review May 10, 2017)


The relation between structural and functional connectivity has profound implications for our understanding of cerebral physiology and cognitive neuroscience. Yet, this relation remains incompletely understood. Cases in which the corpus callosum is sectioned for medical reasons provide a unique opportunity to study this question. We report functional connectivity assessed before and after surgical section of the corpus callosum, including multiyear follow-up in a limited subsample. Our results demonstrate a causal role for the corpus callosum in maintaining functional connectivity between the hemispheres. Additionally, comparison of results obtained in complete vs. partial callosotomy demonstrate that polysynaptic connections also play a role in maintaining interhemispheric functional connectivity.


Resting state functional connectivity is defined in terms of temporal correlations between physiologic signals, most commonly studied using functional magnetic resonance imaging. Major features of functional connectivity correspond to structural (axonal) connectivity. However, this relation is not one-to-one. Interhemispheric functional connectivity in relation to the corpus callosum presents a case in point. Specifically, several reports have documented nearly intact interhemispheric functional connectivity in individuals in whom the corpus callosum (the major commissure between the hemispheres) never develops. To investigate this question, we assessed functional connectivity before and after surgical section of the corpus callosum in 22 patients with medically refractory epilepsy. Section of the corpus callosum markedly reduced interhemispheric functional connectivity. This effect was more profound in multimodal associative areas in the frontal and parietal lobe than primary regions of sensorimotor and visual function. Moreover, no evidence of recovery was observed in a limited sample in which multiyear, longitudinal follow-up was obtained. Comparison of partial vs. complete callosotomy revealed several effects implying the existence of polysynaptic functional connectivity between remote brain regions. Thus, our results demonstrate that callosal as well as extracallosal anatomical connections play a role in the maintenance of interhemispheric functional connectivity.


  • ?1To whom correspondence should be addressed. Email: rolandj{at}wustl.edu.
  • Author contributions: J.L.R., J.S.S., D.D.L., M.E.R., M.D.S., and E.C.L. designed research; J.L.R., A.Z.S., A.M., D.D.L., and M.D.S. performed research; J.L.R., A.Z.S., C.D.H., D.D.L., and M.D.S. contributed new reagents/analytic tools; J.L.R., A.Z.S., C.D.H., A.M., and E.C.L. analyzed data; and J.L.R., A.Z.S., and E.C.L. wrote the paper.

  • Conflict of interest statement: E.C.L. discloses financial relationships with the following companies: Intellectual Ventures, Monteris Medical, Acera Medical, Pear Therapeutics, General Sensing, Immunovalent, Face to Face Biometrics, Neurolutions, and Osteovantage.

  • This article is a PNAS Direct Submission. M.T.d.S. is a guest editor invited by the Editorial Board.

  • This article contains supporting information online at www.danielhellerman.com/lookup/suppl/doi:10.1073/pnas.1707050114/-/DCSupplemental.

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