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 to check access.
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.
Allman JM, Hakeem A, Watson KK (2002) Two phylogenetic specializations in the human brain. Neuroscientist 8:335–346PubMedCrossRefGoogle Scholar
Hakeem AY, Sherwood CC, Bonar CJ, Hof PR, Allman JM (2008) Von Economo neurons in the elephant brain. Anat Rec (in press)Google Scholar
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.20407CrossRefGoogle Scholar
Jeret JS, Serur D, Wisniewski KE, Lubin RA (1987) Clinicopathological findings associated with agenesis of the corpus callosum. Brain Dev 9:255–264PubMedGoogle Scholar
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.10014PubMedCrossRefGoogle Scholar
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 235–246Google Scholar
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/nrn2107PubMedCrossRefGoogle Scholar
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 127–150Google Scholar
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/13.2.115PubMedCrossRefGoogle Scholar
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 221–233Google Scholar
Saul RE, Sperry RW (1968) Absence of commissurotomy symptoms with agenesis of the corpus callosum. Neurology 18:307PubMedGoogle Scholar
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–S57PubMedGoogle Scholar
Watson KK, Matthews BJ, Allman JM (2006) Brain activation during sight gags and language-dependent humor. Cereb Cortex (in press)Google Scholar
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.1092310411PubMedCrossRefGoogle Scholar
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 161–174Google Scholar