Daniel Manrique-Castano, Neuroscientist, Germany

16 April 2020

This article was originally published in Spanish at https://hablemosdeneurociencia.com/cerebro-desconocido-neuronas-von/

At the end of the 19th century, the Ukrainian anatomist Vladimir Betz described a group of cells that attracted his attention because of their shape: “These spindle cells of the cingulate gyrus are notably larger (two or three times) than the other neurons of the V plate” [4]. Similarly, the Spanish neuroanatomist Santiago Ramón y Cajal referred to them as “giant spindle cells” during his histological studies of the cerebral cortex [5].

However, it was the Austrian psychiatrist and neurologist Constantin von Economo who provided a detailed description of the morphology and location of this type of cell in the cerebral cortex of the adult human. In a 1925 paper entitled Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen (The Cytoarchitecture of the Crust of the Adult Human), this scientist described these cells as spindle elongated neurons (spindle-shaped) reaching 70-100 µm, which makes them four times larger than a pyramidal cell of the V-layer.


What makes Von Economo Neurons special?

In 1926 in Eine neue Art Spezialzellen des Lobus cinguli und Lobus insulae (a new type of special cells in the cingulate and insular lobes), Von Economo writes: “Years ago, I discovered a particular type of cell, the lamina V of the anterior rostral cingulate, which, as far as I could find in the literature, had not been previously described and which I mistakenly thought was a pathological formation. Since then, I have completed a detailed analysis of the architecture of the entire cerebral cortex in a large number of adult brains; this analysis shows that this particular type of cell is in fact specialized in the cingulate gyrus and is found only in another gyrus, the insular gyrus” [14]. In 2005, a group of researchers renamed these giant V-layer spindle cells as Von Economo Neurons (VENs), in recognition of the work of the Austrian neurologist [2].

Despite this early 20th century report, VENs were overlooked in most neuroscience studies until computer mapping of the brain made it possible to identify them as projection neurons located in the Vb layer of the anterior cingulate cortex [10] and the insula [9]. Since then, they have gained importance especially in the field of cognitive sciences and neuropsychiatry. The reason is that they have been found only in animals with superior cognitive and social behaviors. Since 2006, VENs have been found in whales, elephants, dolphins, manatees, and primates. In particular, in 2008, my colleague and friend Camilo Fajardo, in Colombia, discovered this type of cell in the dorsolateral cortex of the human prefrontal cortex [8]. Interestingly, it is estimated that this cell’s lineage originated 15 million years ago with Dryopitecus (a common hominid ancestor) [3].

VENs have been found to be more abundant in humans and other primates such as bonobos, chimpanzees, and gorillas, compared to non-primate species. In primates, these cells are found in clusters of three to six neurons, constituting about 5% of the total pyramidal cells in the V plate. In addition, the number and structure of VENs have been found to be species-specific [1]. These cells appear in prenatal development (week 35) and increase to their described number in adulthood at 4 years of age. Interestingly, it has been found that it takes 8 months (postnatal) for humans to reach the number of VENs of a chimp at birth. Similarly, it has been observed that in neonates the number of VENs is similar in both hemispheres, while later an asymmetry is observed favoring the right hemisphere [1].

“Von Economo neurons have been found only in animals with superior cognitive and social behaviors”

What are the characteristics of Von Economo neurons?

The fine architecture of VENs was recently described by Karli Watson as part of her dissertation for a PhD in neurobiology at the California Institute of Technology (CALTECH). In her paper, the biologist described VENs as having basal and apical dendrites with simple arborization and reduced dendritic spines. In addition, the length of the dendrites is less than the pyramidal cells of the same lamina. It is speculated that these characteristics make them integrate a reduced number of inputs and generate fast conduction with a long axon [5]. They are generally larger than the pyramidal cells of lamina V and the spindle cells of lamina VI, and are more numerous in the right hemisphere.

Unlike other spindle cells, VENs are not inhibitory; expression of MAP2 (Microtubule-associated protein 2) and staining with DiI evidence that they are projection cells [6]. In addition, immunohistochemical processes have revealed that they express vasopressin, dopamine and serotonin receptors, although no specific neurotransmitter synthesized by these cells has been described [2].

Von Economo Neuron stained in the macaque brain 

Henry Evrard / Max Planck Institute for Biological Cybernetics

Von Economo Neurons and the human mind 

Some scientists consider Von Economo neurons to be important links in understanding the evolution of the human brain and mind. It has been suggested that these neurons are involved in the most advanced human features or higher cognitive processes and that they may play a major role in the neural correlates of consciousness [7]. In recent years, the possibility that VENs are related to various psychiatric disorders has been explored. Although most studies relate these cells to cingulate and island-crust dependent pathologies, a clear role for VENs has not been described. Nevertheless, it is suggested that they have a broad correlation with the autism spectrum and are particularly susceptible to Alzheimer’s disease, where 60% of the total VEN population is lost [5].

However, a greater number of VENs have been found in suicidal people diagnosed with psychotic disorders than in people with the same disorder who died from other causes. This has allowed some researchers to theorize about the role of VENs in higher cognitive processes such as self-assessment [5]. Using post-mortem brains of young people diagnosed with autism, a study showed that patients had a higher rate of VENs/pyramidal neurons than control subjects. This led scientists to hypothesize that autism may be related to the abnormal production of NDVs during development [12].

Von Economo Neurons (VENs) represent a special challenge in neuroscience research. Because they are only present in primates and other higher mammals such as dolphins, whales, and elephants, their research is limited by ethical and economic standards, unlike other cell types that can be studied in rodents. The fact that they are present in the later evolutionary stages of species with superior cognitive processes and a high rate of social behavior makes VENs especially attractive in the field of cognitive sciences. Perhaps in the not too distant future, it will be discovered that a single cell type has the power to make us human.


[1] Allman, J.M., Tetreault, N.A., Hakeem, A.Y., Manaye, K.F., Semendeferi, K., Erwin, J.M., et al. (2010). The von Economo neurons in frontoinsular and anterior cingulate cortex of great apes and humans. Brain Structure and Function, 214(5e6), 495e517.

[2] Allman, J.M., Watson, K.K., Tetreault, N.A., Hakeem, A.Y. (2005). Intuition and autism: a possible role for Von Economo neurons. Trends in Cognitive Science, 9(8).

[3] Brüne, M., Schöbel, A., Karau, R., Faustmann, P. M., Dermietzel, R., Juckel, G., & Petrasch-Parwez, E. (2011). Neuroanatomical correlates of suicide in psychosis: the possible role of von Economo neurons. PloS One, 6(6), e20936.

[4] Butti, C., Santos, M., Uppal, N., & Hof, P. R. (2013). Von Economo neurons: clinical and evolutionary perspectives. Cortex, 49(1), 312–26.

[5] Craig, A. A. (2009). How do you feel — now? The anterior insular and human awareness. Nature Reviews Neuroscience, 10(1),59—70.

[6] Fajardo, C., Escobar, M. I., Buriticá, E., Arteaga, G., Umbarila, J., Casanova, M. F., & Pimienta, H. (2008). Von Economo neurons are present in the dorsolateral (dysgranular) prefrontal cortex of humans. Neuroscience Letters, 435(3), 215–8.

[7] Pauc, R., & Young, A. (2009). The history of von Economo neurons (VENs) and their possible role in neurodevelopmental/neuropsychiatric disorders: A literature review. Clinical Chiropractic, 12(3), 101–108.

[8] Santos, M., Uppal, N., Butti, C., Wicinski, B., Schmeidler, J., Giannakopoulos, P., … Hof, P. R. (2011). Von Economo neurons in autism: a stereologic study of the frontoinsular cortex in children. Brain Research, 1380, 206–17.

[9] Watson, Karli Kiiko(2006)The von Economo neurons : from cells to behavior. Disertación doctoral, California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05252006-224259

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