Skip to main content
SpringerLink
Log in

Selective reduction of Von Economo neuron number in agenesis of the corpus callosum

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Von Economo neurons (VENs) are large spindle-shaped neurons localized to anterior cingulate cortex (ACC) and fronto-insular cortex (FI). VENs appear late in development in humans, are a recent phylogenetic specialization, and are selectively destroyed in frontotemporal dementia, a disease which profoundly disrupts social functioning and self-awareness. Agenesis of the corpus callosum (AgCC) is a congenital disorder that can have significant effects on social and emotional behaviors, including alexithymia, difficulty intuiting the emotional states of others, and deficits in self- and social-awareness that can impair humor, comprehension of non-literal or affective language, and social judgment. To test the hypothesis that VEN number is selectively reduced in AgCC, we used stereology to obtain unbiased estimates of total neuron number and VEN number in postmortem brain specimens of four normal adult controls, two adults with isolated callosal dysgenesis, and one adult whose corpus callosum and ACC were severely atrophied due to a non-fatal cerebral arterial infarction. The partial agenesis case had approximately half as many VENs as did the four normal controls, both in ACC and FI. In the complete agenesis case the VENs were almost entirely absent. The percentage of neurons in FI that are VENs was reduced in callosal agenesis, but was actually slightly above normal in the stroke patient. These results indicate that the VEN population is selectively reduced in AgCC, but that the VENs do not depend on having an intact corpus callosum. We conclude that in agenesis of the corpus callosum the reduction in the number of VENs is not the direct result of the failure of this structure to develop, but may instead be another consequence of the genetic disruption that caused the agenesis. The reduction of the VEN population could help to explain some of the social and emotional deficits that are seen in this disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Allman JM, Hakeem A, Watson KK (2002) Two phylogenetic specializations in the human brain. Neuroscientist 8:335–346

    Article  PubMed  Google Scholar 

  2. Allman JM, Watson KK, Tetreault NA, Hakeem AY (2005) Intuition and autism: a possible role for Von Economo neurons. Trends Cogn Sci 9:367–373. doi:10.1016/j.tics.2005.06.008

    Article  PubMed  Google Scholar 

  3. Bartels A, Zeki S (2000) The neural basis of romantic love. Neuroreport 11:3829–3834. doi:10.1097/00001756-200011270-00046

    Article  PubMed  CAS  Google Scholar 

  4. Berthoz S, Armony JL, Blair RJ, Dolan RJ (2002) An fMRI study of intentional and unintentional (embarrassing) violations of social norms. Brain 125:1696–1708. doi:10.1093/brain/awf190

    Article  PubMed  CAS  Google Scholar 

  5. Brown WS, Paul LK (2000) Cognitive and psychosocial deficits in agenesis of the corpus callosum with normal intelligence. Cognit Neuropsychiatry 5:135–157. doi:10.1080/135468000395781

    Article  Google Scholar 

  6. Brown WS, Paul LK, Symington M, Dietrich R (2005) Comprehension of humor in primary agenesis of the corpus callosum. Neuropsychologia 43:906–916. doi:10.1016/j.neuropsychologia.2004.09.008

    Article  PubMed  Google Scholar 

  7. Chiarello C (1980) A house divided? Cognitive functioning with callosal agenesis. Brain Lang 11:128–158. doi:10.1016/0093-934X(80)90116-9

    Article  PubMed  CAS  Google Scholar 

  8. David AS, Wacharasindhu A, Lishman WA (1993) Severe psychiatric disturbance and abnormalities of the corpus callosum: review and case series. J Neurol Neurosurg Psychiatry 56:85–93

    PubMed  CAS  Google Scholar 

  9. Dennis M (1981) Language in congenitally acallosal brain. Brain Lang 12:33–53. doi:10.1016/0093-934X(81)90004-3

    Article  PubMed  CAS  Google Scholar 

  10. Devinsky O, Laff R (2003) Callosal lesions and behavior: history and modern concepts. Epilepsy Behav 4:607–617. doi:10.1016/j.yebeh.2003.08.029

    Article  PubMed  Google Scholar 

  11. Duan X, Chang JH, Ge S et al (2007) Disrupted-in-schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 130:1146–1158. doi:10.1016/j.cell.2007.07.010

    Article  PubMed  CAS  Google Scholar 

  12. Ettlinger G (1977) Agenesis of the corpus callosum. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 30. Elsevier, Amsterdam, pp 285–297

    Google Scholar 

  13. Fischer M, Ryan SB, Dobyns WB (1992) Mechanisms of interhemispheric transfer and patterns of cognitive function in acallosal patients of normal intelligence. Arch Neurol 49:271–277

    PubMed  CAS  Google Scholar 

  14. Gilliam F, Wyllie E, Kotagal P, Geckler C, Rusyniak G (1996) Parental assessment of functional outcome after corpus callosotomy. Epilepsia 37:753–757. doi:10.1111/j.1528-1157.1996.tb00647.x

    Article  PubMed  CAS  Google Scholar 

  15. Gott PS, Saul RE (1978) Agenesis of the corpus callosum: limits of functional compensation. Neurology 28:1272–1279

    PubMed  CAS  Google Scholar 

  16. Gundersen HJ, Jensen EB, Kieû K, Nielsen J (1999) The efficiency of systematic sampling in stereology—reconsidered. J Microsc 193:199–211. doi:10.1046/j.1365-2818.1999.00457.x

    Article  PubMed  CAS  Google Scholar 

  17. Hakeem AY, Sherwood CC, Bonar CJ, Hof PR, Allman JM (2008) Von Economo neurons in the elephant brain. Anat Rec (in press)

  18. Hof PR, Van der Gucht E (2007) Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anat Rec 290:1–31. doi:10.1002/ar.20407

    Article  Google Scholar 

  19. Hoppe KB, Bogen JE (1977) Alexithymia in 12 commissurotomized patients. Psychother Psychosom 28:148–155

    Article  PubMed  CAS  Google Scholar 

  20. Jeeves MA (1994) Callosal agenesis—a natural split brain: overview. In: Lassonde M, Jeeves MA (eds) Callosal agenesis—a natural split brain?. Plenum Press, New York, pp 285–299

    Google Scholar 

  21. Jeeves MA, Temple CM (1987) A further study of language function in callosal agenesis. Brain Lang 32:325–335. doi:10.1016/0093-934X(87)90131-3

    Article  PubMed  CAS  Google Scholar 

  22. Jeret JS, Serur D, Wisniewski KE, Lubin RA (1987) Clinicopathological findings associated with agenesis of the corpus callosum. Brain Dev 9:255–264

    PubMed  CAS  Google Scholar 

  23. Karama S, Lecours AR, Leroux J, Bourgouin P, Beaudoin G, Joubert S et al (2002) Areas of brain activation in males and females during viewing of erotic film excerpts. Hum Brain Mapp 16:1–13. doi:10.1002/hbm.10014

    Article  PubMed  Google Scholar 

  24. Lassonde M, Sauerwein C (1997) Neuropsychological outcome of corpus callosotomy in children and adolescents. J Neurosurg Sci 41:67–73. doi:10.1097/00006123-199707000-00014

    Article  PubMed  CAS  Google Scholar 

  25. Loeser JD, Alvord EC (1968) Agenesis of the corpus callosum. Brain 91:553–570. doi:10.1093/brain/91.3.553

    Article  PubMed  CAS  Google Scholar 

  26. Lough S, Kipps CM, Treise C, Watson P, Blair JR, Hodges JR (2006) Social reasoning, emotion and empathy in frontotemporal dementia. Neuropsychologia 44:950–958. doi:10.1016/j.neuropsychologia.2005.08.009

    Article  PubMed  Google Scholar 

  27. Meyer BU, Roricht S, Niehaus L (1998) Morphology of acallosal brains as assessed by MRI in six patients leading a normal daily life. J Neurol 245:106–110. doi:10.1007/s004150050187

    Article  PubMed  CAS  Google Scholar 

  28. Miller BL, Seeley WW, Mychack P, Rosen HJ, Mena I, Boone K (2001) Neuroanatomy of the self: evidence from patients with frontotemporal dementia. Neurology 57:817–821

    PubMed  CAS  Google Scholar 

  29. Nimchinsky EA, Gilissen E, Allman JM, Perl DP, Erwin JM, Hof PR (1999) A neuronal morphologic type unique to humans and great apes. Proc Natl Acad Sci USA 96:5268–5273. doi:10.1073/pnas.96.9.5268

    Article  PubMed  CAS  Google Scholar 

  30. Nimchinsky EA, Vogt BA, Morrison JH, Hof PR (1995) Spindle neurons of the human anterior cingulate cortex. J Comp Neurol 355:27–37. doi:10.1002/cne.903550106

    Article  PubMed  CAS  Google Scholar 

  31. O’Brien G (1994) The behavioral and developmental consequences of corpus callosum agenesis and Aicardi Syndrome. In: Lassonde M, Jeeves MA (eds) Callosal agenesis: a natural split brain?. Plenum, New York, pp 235–246

    Google Scholar 

  32. Paul LK, Brown WS, Adolphs R, Tyszka JM, Richards LJ, Mukherjee P et al (2007) Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nat Rev Neurosci 8:287–299. doi:10.1038/nrn2107

    Article  PubMed  CAS  Google Scholar 

  33. Paul LK, Schieffer B, Brown WS (2004) Social processing deficits in agenesis of the corpus callosum: narratives from the thematic appreciation test. Arch Clin Neuropsychol 19:215–225. doi:10.1016/S0887-6177(03)00024-6

    Article  PubMed  Google Scholar 

  34. Paul LK, Van Lancker-Sidtis D, Schieffer B, Dietrich R, Brown WS (2003) Communicative deficits in agenesis of the corpus callosum: nonliteral language and affective prosody. Brain Lang 85:313–324. doi:10.1016/S0093-934X(03)00062-2

    Article  PubMed  Google Scholar 

  35. Rakic P (1984) Emergence of neuronal and glial cell lineages in primate brain. In: Black IB (ed) Cellular and molecular biology of neural development. Plenum Press, New York

    Google Scholar 

  36. Rankin KP, Gorno-Tempini ML, Allison SC, Stanley CM, Glenn S, Weiner MW et al (2006) Structural anatomy of empathy in neurodegenerative disease. Brain 129:2945–2956. doi:10.1093/brain/awl254

    Article  PubMed  Google Scholar 

  37. Rose JE, Woolsey CN (1948) Structure and relations of limbic cortex and anterior thalamic nuclei in rabbit and cat. J Comp Neurol 89:279–347. doi:10.1002/cne.900890307

    Article  PubMed  CAS  Google Scholar 

  38. Rose JE, Woolsey CN (1958) Cortical connections and functional organization of thalamic auditory system of cat. In: Harlow HF, Woolsey CN (eds) Biological and biochemical bases of behavior. University of Wisconsin Press, Madison, pp 127–150

    Google Scholar 

  39. Samuelsen GB, Larsen KB, Bogdanovic N, Laursen H, Graem N, Larsen JF et al (2003) The changing number of cells in the human fetal forebrain and its subdivisions: a stereological analysis. Cereb Cortex 13:115–122. doi:10.1093/cercor/13.2.115

    Article  PubMed  Google Scholar 

  40. Sanders RJ (1989) Sentence comprehension following agenesis of the corpus callosum. Brain Lang 37:59–72. doi:10.1016/0093-934X(89)90101-6

    Article  PubMed  CAS  Google Scholar 

  41. Sauerwein HC, Nolin P, Lassonde M (1994) Cognitive functioning in callosal agenesis. In: Lassonde M, Jeeves MA (eds) Callosal agenesis: a natural split brain?. Plenum, New York, pp 221–233

    Google Scholar 

  42. Saul RE, Sperry RW (1968) Absence of commissurotomy symptoms with agenesis of the corpus callosum. Neurology 18:307

    PubMed  CAS  Google Scholar 

  43. Schmitz C, Hof PR (2005) Design-based stereology in neuroscience. Neuroscience 130:813–831. doi:10.1016/j.neuroscience.2004.08.050

    Article  PubMed  CAS  Google Scholar 

  44. Seeley WW, Carlin DA, Allman JM, Macedo MN, Bush C, Miller BL et al (2006) Early frontotemporal dementia targets neurons unique to apes and humans. Ann Neurol 60:660–667. doi:10.1002/ana.21055

    Article  PubMed  Google Scholar 

  45. Seeley WW, Allman JM, Carlin DA et al (2007) Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution. Alzheimer Dis Assoc Disord 21:S50–S57

    PubMed  Google Scholar 

  46. Shin LM, Dougherty DD, Orr SP, Pitman RK, Lasko M, Macklin ML et al (2000) Activation of anterior paralimbic structures during guilt-related script-driven imagery. Biol Psychiatry 48:43–50. doi:10.1016/S0006-3223(00)00251-1

    Article  PubMed  CAS  Google Scholar 

  47. Singer T, Seymour B, O’Doherty J, Kaube H, Dolan RJ, Frith CD (2004) Empathy for pain involves the affective but not sensory components of pain. Science 303:1157–1162. doi:10.1126/science.1093535

    Article  PubMed  CAS  Google Scholar 

  48. Singer T, Seymour B, O’Doherty JP, Stephan KE, Dolan RJ, Frith CD (2006) Empathic neural responses are modulated by the perceived fairness of others. Nature 439:466–469. doi:10.1038/nature04271

    Article  PubMed  CAS  Google Scholar 

  49. Snowden JS, Gibbons ZC, Blackshaw A, Doubleday E, Thompson J, Craufurd D et al (2003) Social cognition in frontotemporal dementia and Huntington’s disease. Neuropsychologia 41:688–701. doi:10.1016/S0028-3932(02)00221-X

    Article  PubMed  CAS  Google Scholar 

  50. Sokal RR, Rohlf FJ (1995) Biometry: the priciples and practice of statistics in biological research. W.H. Freeman, New York

    Google Scholar 

  51. Sturm VE, Rosen HJ, Allison S, Miller BL, Levenson RW (2006) Self-conscious emotion deficits in frontotemporal lobar degeneration. Brain 129:2508–2516. doi:10.1093/brain/awl145

    Article  PubMed  Google Scholar 

  52. Taylor M, David AS (1998) Agenesis of the corpus callosum: a United Kingdom series of 56 cases. J Neurol Neurosurg Psychiatry 64:131–134

    PubMed  CAS  Google Scholar 

  53. Temple CM, Ilsley J (1993) Phonemic discrimination in callosal agenesis. Cortex 29:341–348

    PubMed  CAS  Google Scholar 

  54. Temple CM, Jeeves MA, Vilarroya O (1989) Ten pen men: rhyming skills in two children with callosal agenesis. Brain Lang 37:548–564. doi:10.1016/0093-934X(89)90111-9

    Article  PubMed  CAS  Google Scholar 

  55. Temple CM, Jeeves MA, Vilarroya OO (1990) Reading in callosal agenesis. Brain Lang 39:235–253. doi:10.1016/0093-934X(90)90013-7

    Article  PubMed  CAS  Google Scholar 

  56. TenHouten WD, Hoppe KD, Bogen JE, Walter DO (1986) Alexithymia: an experimental study of cerebral commissurotomy patients and normal control subjects. Am J Psychiatry 143:312–316

    PubMed  CAS  Google Scholar 

  57. Tomasch J (1954) Size, distribution, and number of fibers in the human corpus callosum. Anat Rec 119:119–135. doi:10.1002/ar.1091190109

    Article  PubMed  CAS  Google Scholar 

  58. Von Economo C, Koskinas G (1925) Die Cytoarchitectonik der Hirnrinde des erwachsenen Menschen. Springer

  59. Watson KK, Jones TK, Allman JM (2006) Dendritic architecture of the von Economo neurons. Neuroscience 141:1107–1112. doi:10.1016/j.neuroscience.2006.04.084

    Article  PubMed  CAS  Google Scholar 

  60. Watson KK, Matthews BJ, Allman JM (2006) Brain activation during sight gags and language-dependent humor. Cereb Cortex (in press)

  61. West MJ, Slomianka L, Gundersen HJG (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497. doi:10.1002/ar.1092310411

    Article  PubMed  CAS  Google Scholar 

  62. Zaidel DW (1995) A view of the world from a split-brain perspective. In: Critchley EMR (ed) The neurological boundaries of reality. Jason Aronson, Northvale, pp 161–174

    Google Scholar 

Download references

Acknowledgments

We thank Archibald Fobbs, Curator of the Yakovlev Brain Collection, National Museum of Health and Medicine for his generous assistance in providing access to the acallosal and control specimens, and to Dr. D. Wolfe of the Mount Sinai School of Medicine for generously providing access to the cerebral infarction specimen. We also wish to thank Ralph Adolphs, Warren Brown and J. Michael Tyszka for their valuable discussions of this project. This research was generously funded by grants from the James S. McDonnell Foundation, the Gordon and Betty Moore Foundation, the David and Lucile Packard Foundation, and the Gustavus and Louise Pfeiffer Foundation.

Author information

Authors and Affiliations

  1. Division of Biology, California Institute of Technology, MC 216-76, Pasadena, CA, 91125, USA

    Jason A. Kaufman, Atiya Y. Hakeem & John M. Allman

  2. Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, USA

    Lynn K. Paul

  3. Graduate School of Psychology, Fuller Theological Seminary, Pasadena, USA

    Lynn K. Paul

  4. Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC, USA

    Kebreten F. Manaye

  5. Department of Molecular Biology, Princeton University, Princeton, NJ, USA

    Andrea E. Granstedt

  6. Department of Neuroscience, Mount Sinai School of Medicine, New York, USA

    Patrick R. Hof

Authors
  1. Jason A. Kaufman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lynn K. Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kebreten F. Manaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrea E. Granstedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Patrick R. Hof
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Atiya Y. Hakeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. John M. Allman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John M. Allman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaufman, J.A., Paul, L.K., Manaye, K.F. et al. Selective reduction of Von Economo neuron number in agenesis of the corpus callosum. Acta Neuropathol 116, 479–489 (2008). https://doi.org/10.1007/s00401-008-0434-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-008-0434-7

Keywords

Search

Navigation