Brain Structure and Function

, Volume 224, Issue 5, pp 1897–1909 | Cite as

Diffusion weighted imaging evidence of extra-callosal pathways for interhemispheric communication after complete commissurotomy

  • Jason S. NomiEmail author
  • Emily Marshall
  • Eran Zaidel
  • Bharat Biswal
  • F. Xavier Castellanos
  • Anthony Steven Dick
  • Lucina Q. UddinEmail author
  • Eric Mooshagian
Original Article


The integrity of white matter architecture in the human brain is related to cognitive processing abilities. The corpus callosum is the largest white matter bundle interconnecting the two cerebral hemispheres. “Split-brain” patients in whom all cortical commissures have been severed to alleviate intractable epilepsy demonstrate remarkably intact cognitive abilities despite the lack of this important interhemispheric pathway. While it has often been speculated that there are compensatory alterations in the remaining interhemispheric fibers in split-brain patients several years post-commissurotomy, this has never been directly shown. Here we examined extra-callosal pathways for interhemispheric communication in the brain of a patient who underwent complete cerebral commissurotomy using diffusion weighted imaging tractography. We found that compared with a healthy age-matched comparison group, the split-brain patient exhibited increased fractional anisotropy (FA) of the dorsal and ventral pontine decussations of the cortico-cerebellar interhemispheric pathways. Few differences were observed between the patient and the comparison group with respect to FA of other long-range intrahemispheric fibers. These results point to specific cerebellar anatomical substrates that may account for the spared interhemispheric coordination and intact cognitive abilities that have been extensively documented in this unique patient.


Corpus callosum Structural connectivity Interhemispheric transfer Epilepsy Hemispheric specialization Laterality 



The authors thank Anouk Scheres and Scott Squire for assistance with data collection.


This work was supported by a University of Miami Gabelli Senior Scholar Award, an award from the Canadian Institute for Advanced Research, and National Institute of Mental Health [R01MH107549] to LQU. We also acknowledge the Nathan Kline Institute Enhanced Rockland Sample for the availability of age-matched comparison participants, collected with support from R01MH094639.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical 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. This article does not contain any studies with animals performed by any of the authors.


  1. Adamaszek M, D’Agata F, Ferrucci R, Habas C, Keulen S, Kirkby KC, Leggio M, Marien P, Molinari M, Moulton E, Orsi L, Van Overwalle F, Papadelis C, Priori A, Sacchetti B, Schutter DJ, Styliadis C, Verhoeven J (2017) Consensus paper: cerebellum and emotion. Cerebellum 16(2):552–576. CrossRefGoogle Scholar
  2. Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed 15(7–8):435–455. CrossRefGoogle Scholar
  3. Bellebaum C, Daum I (2007) Cerebellar involvement in executive control. Cerebellum 6(3):184–192. CrossRefGoogle Scholar
  4. Bogen JE, Fisher ED, Vogel PJ (1965) Cerebral commissurotomy. A second case report. JAMA 194(12):1328–1329CrossRefGoogle Scholar
  5. Bogen JE, Schultz DH, Vogel PJ (1988) Completeness of callosotomy shown by magnetic resonance imaging in the long term. Arch Neurol 45(11):1203–1205CrossRefGoogle Scholar
  6. Campbell AL Jr, Bogen JE, Smith A (1981) Disorganization and reorganization of cognitive and sensorimotor functions in cerebral commissurotomy. Compensatory roles of the forebrain commissures and cerebral hemispheres in man. Brain 104(3):493–511CrossRefGoogle Scholar
  7. Cheng H, Wang Y, Sheng J, Sporns O, Kronenberger WG, Mathews VP, Hummer TA, Saykin AJ (2012) Optimization of seed density in DTI tractography for structural networks. J Neurosci Methods 203(1):264–272. CrossRefGoogle Scholar
  8. Clarke JM, Zaidel E (1989) Simple reaction times to lateralized light flashes. Varieties of interhemispheric communication routes. Brain 112(Pt 4):849–870CrossRefGoogle Scholar
  9. Clarke JM, Zaidel E (1994) Anatomical-behavioral relationships: corpus callosum morphometry and hemispheric specialization. Behav Brain Res 64(1–2):185–202CrossRefGoogle Scholar
  10. Eviatar Z, Zaidel E (1994) Letter matching within and between the disconnected hemispheres. Brain Cogn 25(1):128–137CrossRefGoogle Scholar
  11. Geschwind N (1965) Disconnexion syndromes in animals and man. I. Brain 88(2):237–294CrossRefGoogle Scholar
  12. Honey CJ, Sporns O, Cammoun L, Gigandet X, Thiran JP, Meuli R, Hagmann P (2009) Predicting human resting-state functional connectivity from structural connectivity. Proc Natl Acad Sci USA 106(6):2035–2040CrossRefGoogle Scholar
  13. Huebner EA, Strittmatter SM (2009) Axon regeneration in the peripheral and central nervous systems. Results Probl Cell Differ 48:339–351. Google Scholar
  14. Jenkinson M, Pechaud M, Smith S (2005) BET2: MR-based estimation of brain, skull and scalp surfaces. In: 11th annual meeting of the organization for human brain mapping, TorontoGoogle Scholar
  15. Jeurissen B, Leemans A, Tournier JD, Jones DK, Sijbers J (2013) Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging. Hum Brain Mapp 34(11):2747–2766. CrossRefGoogle Scholar
  16. Johnston JM, Vaishnavi SN, Smyth MD, Zhang D, He BJ, Zempel JM, Shimony JS, Snyder AZ, Raichle ME (2008) Loss of resting interhemispheric functional connectivity after complete section of the corpus callosum. J Neurosci 28(25):6453–6458. CrossRefGoogle Scholar
  17. Jones DK, Christiansen KF, Chapman RJ, Aggleton JP (2013) Distinct subdivisions of the cingulum bundle revealed by diffusion MRI fibre tracking: implications for neuropsychological investigations. Neuropsychologia 51(1):67–78. CrossRefGoogle Scholar
  18. Keser Z, Hasan KM, Mwangi BI, Kamali A, Ucisik-Keser FE, Riascos RF, Yozbatiran N, Francisco GE, Narayana PA (2015) Diffusion tensor imaging of the human cerebellar pathways and their interplay with cerebral macrostructure. Front Neuroanat 9:41. CrossRefGoogle Scholar
  19. Leitner Y, Travis KE, Ben-Shachar M, Yeom KW, Feldman HM (2015) Tract profiles of the cerebellar white matter pathways in children and adolescents. Cerebellum 14(6):613–623. CrossRefGoogle Scholar
  20. Nooner KB, Colcombe SJ, Tobe RH, Mennes M, Benedict MM, Moreno AL, Panek LJ, Brown S, Zavitz ST, Li Q, Sikka S, Gutman D, Bangaru S, Schlachter RT, Kamiel SM, Anwar AR, Hinz CM, Kaplan MS, Rachlin AB, Adelsberg S, Cheung B, Khanuja R, Yan C, Craddock CC, Calhoun V, Courtney W, King M, Wood D, Cox CL, Kelly AM, Di Martino A, Petkova E, Reiss PT, Duan N, Thomsen D, Biswal B, Coffey B, Hoptman MJ, Javitt DC, Pomara N, Sidtis JJ, Koplewicz HS, Castellanos FX, Leventhal BL, Milham MP (2012) The NKI-rockland sample: a model for accelerating the pace of discovery science in psychiatry. Front Neurosci 6:152. CrossRefGoogle Scholar
  21. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 9:97–113CrossRefGoogle Scholar
  22. O’Reilly JX, Croxson PL, Jbabdi S, Sallet J, Noonan MP, Mars RB, Browning PG, Wilson CR, Mitchell AS, Miller KL, Rushworth MF, Baxter MG (2013) Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys. Proc Natl Acad Sci USA 110(34):13982–13987. CrossRefGoogle Scholar
  23. Palesi F, De Rinaldis A, Castellazzi G, Calamante F, Muhlert N, Chard D, Tournier JD, Magenes G, D’Angelo E, Gandini Wheeler-Kingshott CAM (2017) Contralateral cortico-ponto-cerebellar pathways reconstruction in humans in vivo: implications for reciprocal cerebro-cerebellar structural connectivity in motor and non-motor areas. Sci Rep 7(1):12841. CrossRefGoogle Scholar
  24. Propper RE, O’Donnell LJ, Whalen S, Tie Y, Norton IH, Suarez RO, Zollei L, Radmanesh A, Golby AJ (2010) A combined fMRI and DTI examination of functional language lateralization and arcuate fasciculus structure: effects of degree versus direction of hand preference. Brain Cogn 73(2):85–92. CrossRefGoogle Scholar
  25. Rodrigo S, Oppenheim C, Chassoux F, Golestani N, Cointepas Y, Poupon C, Semah F, Mangin JF, Le Bihan D, Meder JF (2007) Uncinate fasciculus fiber tracking in mesial temporal lobe epilepsy. Initial findings. Eur Radiol 17(7):1663–1668. CrossRefGoogle Scholar
  26. Roland JL, Snyder AZ, Hacker CD, Mitra A, Shimony JS, Limbrick DD, Raichle ME, Smyth MD, Leuthardt EC (2017) On the role of the corpus callosum in interhemispheric functional connectivity in humans. Proc Natl Acad Sci USA 114(50):13278–13283. CrossRefGoogle Scholar
  27. Ruddy KL, Leemans A, Carson RG (2017) Transcallosal connectivity of the human cortical motor network. Brain Struct Funct 222(3):1243–1252. CrossRefGoogle Scholar
  28. Scholz J, Klein MC, Behrens TE, Johansen-Berg H (2009) Training induces changes in white-matter architecture. Nat Neurosci 12(11):1370–1371. CrossRefGoogle Scholar
  29. Shadmehr R (2017) Distinct neural circuits for control of movement vs. holding still. J Neurophysiol 117(4):1431–1460. CrossRefGoogle Scholar
  30. Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17(3):143–155. CrossRefGoogle Scholar
  31. Sokolov AA, Miall RC, Ivry RB (2017) The cerebellum: adaptive prediction for movement and cognition. Trends Cogn Sci 21(5):313–332. CrossRefGoogle Scholar
  32. Uddin LQ (2013) Complex relationships between structural and functional brain connectivity. Trends Cogn Sci 17(12):600–602. CrossRefGoogle Scholar
  33. Uddin LQ, Mooshagian E, Zaidel E, Scheres A, Margulies DS, Kelly AM, Shehzad Z, Adelstein JS, Castellanos FX, Biswal BB, Milham MP (2008) Residual functional connectivity in the split-brain revealed with resting-state functional MRI. NeuroReport 19(7):703–709. CrossRefGoogle Scholar
  34. Uddin LQ, Supekar KS, Ryali S, Menon V (2011) Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development. J Neurosci 31(50):18578–18589. CrossRefGoogle Scholar
  35. Vias C, Dick AS (2017) Cerebellar contributions to language in typical and atypical development: a review. Dev Neuropsychol 42(6):404–421. CrossRefGoogle Scholar
  36. Wedeen VJ, Wang RP, Schmahmann JD, Benner T, Tseng WY, Dai G, Pandya DN, Hagmann P, D’Arceuil H, de Crespigny AJ (2008) Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers. NeuroImage 41(4):1267–1277. CrossRefGoogle Scholar
  37. Yeh FC, Verstynen TD, Wang Y, Fernandez-Miranda JC, Tseng WY (2013) Deterministic diffusion fiber tracking improved by quantitative anisotropy. PLoS One 8(11):e80713. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of MiamiCoral GablesUSA
  2. 2.Department of PsychologyUniversity of CaliforniaLos AngelesUSA
  3. 3.Brain Research InstituteUniversity of CaliforniaLos AngelesUSA
  4. 4.Department of Biomedical EngineeringNew Jersey Institute of TechnologyNewarkUSA
  5. 5.Department of Child and Adolescent PsychiatryHassenfeld Children’s Hospital at NYU LangoneNew YorkUSA
  6. 6.Nathan Kline Institute for Psychiatric ResearchOrangeburgUSA
  7. 7.Department of PsychologyFlorida International UniversityMiamiUSA
  8. 8.Neuroscience ProgramUniversity of Miami Miller School of MedicineMiamiUSA
  9. 9.Department of NeuroscienceWashington University School of MedicineSaint LouisUSA

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