Split-Brain Human Subjects

  • Mara Fabri
  • Nicoletta Foschi
  • Chiara Pierpaoli
  • Gabriele Polonara
Part of the Neuromethods book series (NM, volume 122)


This chapter reviews the neuropsychological and imaging studies, carried out by the author’s group and coworkers on split-brain patients in the past 19 years, to investigate the role of the human corpus callosum in the interhemispheric transfer and integration of information. These studies will provide evidence of how the research on split-brain patients may provide a significant contribution to the understanding of lateralized and diffuse brain functions. In particular, by comparing results from total and partial callosotomized patients and with control subjects, many findings have been obtained on the organization and functions of human brain. The studies will be described in a brief overview of other groups’ research on similar patients.

Key words

Corpus callosum Interhemispheric connections fMRI Neuropsychological testing 



Anterior parietal cortex


Blood oxygenation level dependent


Corpus callosum


Cingulated cortex


Central sulcus


Computerized tomography


Crossed uncrossed difference


Diffusion tensor imaging


Functional magnetic resonance imaging


Interhemispheric transfer


Glutamic acid decarboxylase


Left visual field




Magnetic resonance imaging


Posterior callosal body


Postcentral gyrus


Postcentral sulcus


Positron emission tomography


Parietal operculum


Poffenberger paradigm


Posterior parietal cortex


Receptive field


Right hemisphere hypothesis


Region of interest


Reaction time


Redundant target effect


Right visual field


Superior colliculus


Same-different recognition test


Primary somatic sensory area


Secondary somatic sensory area


Sylvian sulcus


Tactile finger localization test


Tactile naming test


Temporal parietal junction


Visual field


Valence hypothesis



The authors wish to thank Professors Tullio Manzoni and Ugo Salvolini for establishing the collaboration, and for providing helpful criticism and support during the research; Drs. Angelo Quattrini, Maria Del Pesce, and Aldo Paggi for encouraging callosotomized patients to participate in the studies; Dr. Giulia Mascioli for her great fMRI processing work and neuropsychological testing; Ms. Gabriella Venanzi for scheduling patient examinations; the technical staff of the Istituto di Radiologia for their invaluable assistance during the scan acquisition; the patients and their families, all the volunteers who participated in the research.


  1. 1.
    Amaral DG (2000) The anatomical organization of the central nervous system. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of neural science, 4th edn. McGraw-Hill, New York, pp 317–336Google Scholar
  2. 2.
    Rogers LJ, Vallortigara G, Andrew RJ (2013) Evolution. In: Rogers LJ, Vallortigara G, Andrew RJ (eds) Divided brains: the biology and behavior of brain asymmetries (Chapter 3). Cambridge University Press, New York, pp 62–97CrossRefGoogle Scholar
  3. 3.
    Kaas JH, Jain N, Qi H-X (2002) The organization of somatosensory system in primates. In: Nelson R (ed) The somatosensory system: deciphering the brain’s own body image. CRC, Boca Raton, FL, pp 1–25Google Scholar
  4. 4.
    Gazzaniga MS (2000) Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition? Brain 123:1293–1326CrossRefPubMedGoogle Scholar
  5. 5.
    Funnell MG, Corballis PM, Gazzaniga MS (2000) Cortical and subcortical interhemispheric interactions following partial and complete callosotomy. Arch Neurol 57:185–189CrossRefPubMedGoogle Scholar
  6. 6.
    Fabri M, Del Pesce M, Paggi A, Polonara G, Bartolini M, Salvolini U, Manzoni T (2005) Contribution of posterior corpus callosum to the interhemispheric transfer of tactile information. Cogn Brain Res 24:73–80CrossRefGoogle Scholar
  7. 7.
    Fabri M, Polonara G, Mascioli G, Salvolini U, Manzoni T (2011) Topographical organization of human corpus callosum: an fMRI mapping study. Brain Res 1370:99–111CrossRefPubMedGoogle Scholar
  8. 8.
    Sperry RW (1974) Lateral specialization in the surgically separated hemispheres. In: Schmitt F, Worden F (eds) Neurosciences third study program. MIT Press, Cambridge, MA, pp 1–12Google Scholar
  9. 9.
    Zaidel E, Iacoboni M, Berman SM, Zaidel DW, Bogen JE (2011) Callosal syndromes. In: Heilman KM, Valenstein E (eds) Clinical neuropsychology. Oxford University Press, Oxford, pp 349–416Google Scholar
  10. 10.
    Fabri M, Pierpaoli C, Barbaresi P, Polonara G (2014) Functional topography of the corpus callosum investigated by DTI and fMRI. World J Radiol 6:895–906CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gazzaniga MS (2005) Forty-five years of split-brain research and still going strong. Nat Rev Neurosci 6:653–659CrossRefPubMedGoogle Scholar
  12. 12.
    Fabri M, Polonara G, Quattrini A, Salvolini U, Del Pesce M, Manzoni T (1999) Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients. Eur J Neurosci 11:3983–3994CrossRefPubMedGoogle Scholar
  13. 13.
    Fabri M, Polonara G, Del Pesce M, Quattrini A, Salvolini U, Manzoni T (2001) Posterior corpus callosum and interhemispheric transfer of somatosensory information: an fMRI and neuropsychological study of a partially callosotomized patient. J Cogn Neurosci 13:1071–1079CrossRefPubMedGoogle Scholar
  14. 14.
    Westerhausen R, Hugdahl K (2008) The corpus callosum in dichotic listening studies of hemispheric asymmetry: a review of clinical and experimental evidence. Neurosci Biobehav Rev 32:1044–1054CrossRefPubMedGoogle Scholar
  15. 15.
    Marzi CA (1999) The Poffenberger paradigm: a first, simple, behavioural tool to study interhemispheric transmission in humans. Brain Res Bull 50:421–422CrossRefPubMedGoogle Scholar
  16. 16.
    Zaidel E, Iacoboni M (2003) Introduction: Poffenberger’s simple reaction time paradigm for measuring interhemispheric transfer time. In: Zaidel E, Iacoboni M (eds) The parallel brain. The cognitive neuroscience of the corpus callosum. MIT Press, Cambridge, MA, pp 1–7Google Scholar
  17. 17.
    Marzi CA, Bisiacchi P, Nicoletti R (1991) Is interhemispheric transfer of visuomotor information asymmetric? Evidence from a meta-analysis. Neuropsychologia 29:1163–1177CrossRefPubMedGoogle Scholar
  18. 18.
    Lassonde MC, Sauerwein HC, Lepore F (2003) Agenesis of the corpus callosum. In: Zaidel E, Iacoboni M (eds) The parallel brain. The cognitive neuroscience of the corpus callosum. The MIT Press, Cambridge, MA, pp 357–369Google Scholar
  19. 19.
    Omura K, Tsukamoto T, Kotani Y, Ohgami Y, Minami M, Inoue Y (2004) Different mechanisms involved in interhemispheric transfer of visuomotor information. NeuroReport 15:2707–2711CrossRefPubMedGoogle Scholar
  20. 20.
    Tettamanti M, Paulesu E, Scifo P, Maravita A, Fazio F, Perani D, Marzi CA (2002) Interhemispheric transmission of visuomotor information in humans: fMRI evidence. J Neurophysiol 88:1051–1058PubMedGoogle Scholar
  21. 21.
    Weber B, Treyer V, Oberholzer N, Jaermann T, Boesiger P, Brugger P, Regard M, Buck A, Savazzi S, Marzi CA (2005) Attention and interhemispheric transfer: a behavioural and fMRI study. J Cogn Neurosci 17:113–123CrossRefPubMedGoogle Scholar
  22. 22.
    Papo I, Quattrini A, Ortenzi A, Paggi A, Rychlicki F, Provinciali L, Del Pesce M, Cesarano C, Fioravanti P (1997) Predictive factors of callosotomy in drug-resistant epileptic patients with a long follow-up. J Neurosurg Sci 41:31–36PubMedGoogle Scholar
  23. 23.
    Quattrini A, Papo I, Paggi A, Ortensi A, Rychlicki F, Fronzoni M, Recchioni MA, Marchioro R, Pauri GL, Bonaparte A, Mancini S (1989) Anterior callosotomy in drug-resistant epilepsy. Adv Epileptol 17:4245Google Scholar
  24. 24.
    Quattrini A, Papo I, Cesarano R, Fioravanti P, Paggi A, Ortensi A, Foschi N, Rychlicky F, Del Pesce M, Pistoli E, Marinelli M (1997) EEG patterns after callosotomy. J Neurosurg Sci 41:85–92PubMedGoogle Scholar
  25. 25.
    Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113CrossRefPubMedGoogle Scholar
  26. 26.
    Làdavas E, Cimatti D, Del Pesce M, Tuozzi G (1993) Emotional evaluation with and without conscious stimulus identification: evidence from a split-brain patient. Cognit Emot 7:95–114CrossRefGoogle Scholar
  27. 27.
    De Guise E, Del Pesce M, Foschi N, Quattrini A, Papo I, Lassonde M (1999) Callosal and cortical contribution to procedural learning. Brain 122:1049–1062CrossRefPubMedGoogle Scholar
  28. 28.
    Arguin M, Lassonde M, Quattrini A, Del Pesce M, Foschi N, Papo I (2000) Divided visuo-spatial attention systems with total and anterior callosotomy. Neuropsychologia 38:283–291CrossRefPubMedGoogle Scholar
  29. 29.
    Aglioti SM, Tassinari G, Fabri M, Del Pesce M, Quattrini A, Manzoni T, Berlucchi G (2001) Taste laterality in the split brain. Eur J Neurosci 13:195–200CrossRefPubMedGoogle Scholar
  30. 30.
    Fabri M, Polonara G, Quattrini A, Salvolini U (2002) Mechanical noxious stimuli cause bilateral activation of parietal operculum in callosotomized subjects. Cereb Cortex 1:446–451CrossRefGoogle Scholar
  31. 31.
    Corballis MC, Corballis PM, Fabri M (2004) Redundancy gain in simple reaction time following partial and complete callosotomy. Neuropsychologia 42:71–81CrossRefPubMedGoogle Scholar
  32. 32.
    Hausmann M, Corballis MC, Fabri M (2003) Line bisection in the split brain. Neuropsychology 17:602–609CrossRefPubMedGoogle Scholar
  33. 33.
    Savazzi S, Marzi CA (2004) The superior colliculus subserves interhemispheric neural summation in both normals and patients with a total section or agenesis of the corpus callosum. Neuropsychologia 42:1608–1618CrossRefPubMedGoogle Scholar
  34. 34.
    Corballis MC, Barnett KJ, Fabri M, Paggi A, Corballis PM (2004) Hemispheric integration and differences in perception of a line-motion illusion in the divided brain. Neuropsychologia 42:1852–1857CrossRefPubMedGoogle Scholar
  35. 35.
    Corballis MC, Corballis PM, Fabri M, Paggi A, Manzoni T (2005) Now you see it, now you don’t: variable hemineglect in a commissurotomized man. Brain Res Cogn Brain Res 25:521–530CrossRefPubMedGoogle Scholar
  36. 36.
    Hausmann M, Corballis MC, Fabri M, Paggi A, Lewald J (2005) Sound lateralization in subjects with callosotomy, callosal agenesis, or hemispherectomy. Brain Res Cogn Brain Res 25:537–546CrossRefPubMedGoogle Scholar
  37. 37.
    Fabri M, Polonara G, Mascioli G, Paggi A, Salvolini U, Manzoni T (2006) Contribution of the corpus callosum to bilateral representation of the trunk midline in the human brain: a fMRI study of callosotomized patients. Eur J Neurosci 23:3139–3148CrossRefPubMedGoogle Scholar
  38. 38.
    Savazzi S, Fabri M, Rubboli G, Paggi A, Tassinari CA, Marzi CA (2007) Interhemispheric transfer following callosotomy in humans: role of the superior colliculus. Neuropsychologia 45:2417–2427CrossRefPubMedGoogle Scholar
  39. 39.
    Ouimet C, Jolicoeur P, Miller J, Ptito A, Paggi A, Foschi N, Ortenzi A, Lassonde M (2009) Sensory and motor involvement in the enhanced redundant target effect: a study comparing anterior- and totally split-brain individuals. Neuropsychologia 47:684–692CrossRefPubMedGoogle Scholar
  40. 40.
    Ouimet C, Jolicoeur P, Lassonde M, Ptito A, Paggi A, Foschi N, Ortenzi A, Miller J (2010) Bimanual crossed-uncrossed difference and asynchrony of normal, anterior- and totally-split-brain individuals. Neuropsychologia 48:3802–3814CrossRefPubMedGoogle Scholar
  41. 41.
    Pizzini FB, Polonara G, Mascioli G, Beltramello A, Foroni R, Paggi A, Salvolini U, Tassinari G, Fabri M (2010) Diffusion tensor tracking of callosal fibers several years after callosotomy. Brain Res 1312:10–71CrossRefPubMedGoogle Scholar
  42. 42.
    Corballis MC, Birse K, Paggi A, Manzoni T, Pierpaoli C, Fabri M (2010) Mirror-image discrimination and reversal in the disconnected hemispheres. Neuropsychologia 48:1664–1669CrossRefPubMedGoogle Scholar
  43. 43.
    Miller MB, Sinnott-Armstrong W, Young L, King D, Paggi A, Fabri M, Polonara G, Gazzaniga MS (2010) Abnormal moral reasoning in complete and partial callosotomy patients. Neuropsychologia 48:2215–2220CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Fabri M, Polonara G (2013) Functional topography of human corpus callosum: an fMRI mapping study. Neural Plast 2013:251308. doi: 10.1155/2013/251308, 15p
  45. 45.
    Polonara G, Mascioli G, Foschi N, Salvolini U, Pierpaoli C, Manzoni T, Fabri M, Barbaresi P (2014) Further evidence for the topography and connectivity of the corpus callosum: an FMRI study of patients with partial callosal resection. J Neuroimaging 25:465–473CrossRefPubMedGoogle Scholar
  46. 46.
    Prete G, D'Ascenzo S, Laeng B, Fabri M, Foschi N, Tommasi L (2015) Conscious and unconscious processing of facial expressions: evidence from two split-brain patients. J Neuropsychol 9:45–63CrossRefPubMedGoogle Scholar
  47. 47.
    Prete G, Marzoli D, Brancucci A, Fabri M, Foschi N, Tommasi L (2014) The processing of chimeric and dichotic emotional stimuli by connected and disconnected cerebral hemispheres. Behav Brain Res 271:354–364CrossRefPubMedGoogle Scholar
  48. 48.
    Prete G, Fabri M, Foschi N, Brancucci A, Tommasi L (2015) The “consonance effect” and the hemispheres: a study on a split-brain patient. Laterality 20:257–269CrossRefPubMedGoogle Scholar
  49. 49.
    Prete G, Laeng B, Fabri M, Foschi N, Tommasi L (2015) Right hemisphere or valence hypothesis, or both? The processing of hybrid faces in the intact and callosotomized brain. Neuropsychologia 68:94–106CrossRefPubMedGoogle Scholar
  50. 50.
    Manzoni T, Barbaresi P, Conti F, Fabri M (1989) The callosal connections of the primary somatosensory cortex and the neural bases of midline fusion. Exp Brain Res 76:251–266CrossRefPubMedGoogle Scholar
  51. 51.
    Manzoni T (1997) The callosal connections of the hierarchically organized somatosensory areas of primates. J Neurosurg Sci 41:1–22CrossRefPubMedGoogle Scholar
  52. 52.
    Polonara G, Fabri M, Manzoni T, Salvolini U (1999) Localization of the first (SI) and second (SII) somatic sensory areas in human cerebral cortex with fMRI. Am J NeuroRadiol 20:199–205PubMedGoogle Scholar
  53. 53.
    Garcha HS, Ettlinger G (1980) Tactile discrimination learning in the monkey: the effects of unilateral or bilateral removals of the second somatosensory cortex (area SII). Cortex 16:397–412CrossRefPubMedGoogle Scholar
  54. 54.
    Hari R, Forss N (1999) Magnetoencephalography in the study of human somatosensory cortical processing. Philos Trans R Soc Lond B 354:1145–1154CrossRefGoogle Scholar
  55. 55.
    Fabri M, Polonara G, Salvolini U, Manzoni T (2005) Bilateral cortical representation of the trunk midline in human first somatic sensory area. Hum Brain Map 25:287–296CrossRefGoogle Scholar
  56. 56.
    Frot M, Mauguière F (1999) Operculo-insular responses to nociceptive skin stimulation in humans. A review of the literature. Neurophysiol Clin 29:401–410CrossRefPubMedGoogle Scholar
  57. 57.
    Ploner M, Schmitz F, Freund HJ, Schnitzler A (2000) Differential organization of touch and pain in human primary somatosensory cortex. J Neurophysiol 83:1770–1776PubMedGoogle Scholar
  58. 58.
    Disbrow EA, Hinkley LBN, Roberts TPL (2003) Ipsilateral representation of oral structures in human anterior parietal somatosensory cortex and integration of inputs across the midline. J Comp Neurol 467:487–495CrossRefPubMedGoogle Scholar
  59. 59.
    Polonara G, Mascioli G, Salvolini U, Fabri M, Manzoni T (2009) Cortical representation of cutaneous receptors in primary somatic sensory cortex of man: a functional imaging study. In: Columbus F (ed) Somatosensory cortex: roles, interventions and traumas. Nova Science Publishers Inc, New York, pp 51–77Google Scholar
  60. 60.
    Lent R, Schmidt SL (1993) The ontogenesis of the forebrain commissures and the determination of brain asymmetries. Prog Neurobiol 40:249–276CrossRefPubMedGoogle Scholar
  61. 61.
    Mihrshahi R (2006) The corpus callosum as an evolutionary innovation. J Exp Zool 306B:8–17CrossRefGoogle Scholar
  62. 62.
    Kaas JH (2004) Evolution of somatosensory and motor cortex in primates. Anat Rec A 281:1148–1156CrossRefGoogle Scholar
  63. 63.
    Fabri M, Manzoni T (2004) GAD immunoreactivity in callosal projecting neurons of cat and rat somatic sensory areas. Neuroscience 123:557–566CrossRefPubMedGoogle Scholar
  64. 64.
    Mascioli G, Berlucchi G, Pierpaoli C, Salvolini U, Barbaresi P, Fabri M, Polonara G (2015) Functional MRI cortical activations from unilateral tactile-taste stimulations of the tongue. Physiol Behav 151:221–229CrossRefPubMedGoogle Scholar
  65. 65.
    Aglioti S, Tassinari G, Corballis M, Berlucchi G (2000) Incomplete gustatory lateralization as shown by analysis of taste discrimination after callosotomy. J Cogn Neurosci 1:238–245CrossRefGoogle Scholar
  66. 66.
    Polonara G, Mascioli G, Paggi A, Tassinari G, Berlucchi G, Salvolini U, Manzoni T, Fabri M (2006) The cortical representation of taste in the human brain: an fMRI study on callosotomized patients. In: 12th annual meeting of human brain mapping organization, Firenze, June 11–15Google Scholar
  67. 67.
    Geffen G, Nilsson J, Quinn K (1985) The effect of lesions of the corpus callosum on finger localization. Neuropsychologia 23:497–514CrossRefPubMedGoogle Scholar
  68. 68.
    Witelson S (1989) Hand and sex differences in the isthmus and genu of the human corpus callosum: a postmortem morphological study. Brain 112:799–835CrossRefPubMedGoogle Scholar
  69. 69.
    Hofer S, Frahm J (2006) Topography of the human corpus callosum revisited. Comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. NeuroImage 32:989–994CrossRefPubMedGoogle Scholar
  70. 70.
    Chao Y-P, Cho K-H, Yeh C-H, Chou K-H, Chen J-H, Lin C-P (2009) Probabilistic topography of human corpus callosum using cytoarchitectural parcellation and high angular resolution diffusion imaging tractography. Hum Brain Mapp 30:3172–3187CrossRefPubMedGoogle Scholar
  71. 71.
    Gosselin N, Samson S, Adolphs R, Noulhiane M, Roy M, Hasboun D, Baulac M, Peretz I (2006) Emotional responses to unpleasant music correlates with damage to the parahippocampal cortex. Brain 129:2585–2592CrossRefPubMedGoogle Scholar
  72. 72.
    Iacoboni M, Zaidel E (2003) Interhemispheric visuo-motor integration in humans: the effect of redundant targets. Eur J Neurosci 17:1981–1986CrossRefPubMedGoogle Scholar
  73. 73.
    Savazzi S, Marzi CA (2002) Speeding up reaction time with invisible stimuli. Curr Biol 12:403–407CrossRefPubMedGoogle Scholar
  74. 74.
    Squire LR (1986) Mechanisms of memory. Science 232:1612–1919CrossRefPubMedGoogle Scholar
  75. 75.
    Squire LR (1992) Declarative and nondeclarative memory: multiple brain systems supporting learning and memory. J Cogn Neurosci 4:232–243CrossRefPubMedGoogle Scholar
  76. 76.
    Pierpaoli C, Ferrante L, Berlucchi G, Ortenzi A, Manzoni T, Fabri M (2011) Imitation strategies in callosotomized patients. IBRO Firenze, July 14–18Google Scholar
  77. 77.
    Fabri M, Polonara G (2008) Role of the corpus callosum in the interhemispheric tranfer of somatosensory information: an fMRI study. In: LN Bakker (ed) Brain Mapping Research Developments. Nova Science Publishers, Inc. NY, pp 77–100Google Scholar

Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Mara Fabri
    • 1
  • Nicoletta Foschi
    • 2
  • Chiara Pierpaoli
    • 1
  • Gabriele Polonara
    • 3
  1. 1.Dipartimento di Medicina sperimentale e clinica, Sezione di Neuroscienze e Biologia cellulareUniversità Politecnica delle MarcheAnconaItaly
  2. 2.Centro Epilessia, Clinica di NeurologiaAzienda Ospedaliera-Universitaria Umberto IAnconaItaly
  3. 3.Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Sezione di Scienze RadiologicheUniversità Politecnica delle MarcheAnconaItaly

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