Original article

Brain Structure and Function

, Volume 214, Issue 5, pp 495-517

Open Access This content is freely available online to anyone, anywhere at any time.

The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

  • John M. AllmanAffiliated withDivision of Biology, 216-76, California Institute of Technology Email author 
  • , Nicole A. TetreaultAffiliated withDivision of Biology, 216-76, California Institute of Technology
  • , Atiya Y. HakeemAffiliated withDivision of Biology, 216-76, California Institute of Technology
  • , Kebreten F. ManayeAffiliated withDepartment of Physiology and Biophysics, College of Medicine, Howard University
  • , Katerina SemendeferiAffiliated withDepartment of Anthropology, University of California, San Diego
  • , Joseph M. ErwinAffiliated withBiomedical Sciences and Pathobiology, Virginia Polytechnic Institute
  • , Soyoung ParkAffiliated withDivision of Biology, 216-76, California Institute of Technology
  • , Virginie GoubertAffiliated withDivision of Biology, 216-76, California Institute of Technology
  • , Patrick R. HofAffiliated withDepartment of Neuroscience, Mount Sinai School of Medicine

Abstract

The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decision-making, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

Keywords

von Economo neurons Fork cells Anterior cingulate cortex Frontoinsular cortex Hominoid brain Disc1 Neuromedin B