Brain Camp Review – Von Economo Neurons

Spindle Cell
While at UCLA we had the pleasure of a lecture by Dr. John Allman of Caltech. Dr. Allman is a worldwide leader in the investigation of Von Economo neurons (VEN) or ‘spindle’ cells. While he was originally slated to give an introductory neuroanatomy lecture, he ended up spending much of the time discussing this very unique cell type.

Von Economo neurons are large bipolar cells that are found in cortical layer V of the anterior cingulate and fronto-insular regions. The cells have also been found in the gray matter of the ventral claustrum, near the amygdala. Originally discovered by Von Economo and Koskinas (1925) the cells are much larger [5x] than comparable layer V pyramidal cells. The size of these cells seems to indicate that they stand ready to send signals very quickly across long distances.

Von Economo cells are not ubiquitous across animal brains. Only humans, great apes, certain whales, and elephants have been shown to possess VENs. The relative number of cells varies by species, with humans having by far the greatest amount – over twice the number of our nearest evolutionary neighbor. One argument is that some aspect of VEN function is giving rise to the cognitive abilities that make us uniquely human.

Of interest developmentally is that not all Von Economo neurons are in place when we are born. Only 15% of the cells seem to be in place at birth. It takes several additional years for the number of cells to rise to adult-like levels. It is unknown if existing cell types are morphing into Von Economo neurons or if new neurons are migrating into place during this time. In either case, VEN development in somewhat protracted compared to other cell types.

In terms of pathology VENs seem to be particularly vulnerable to certain types of disease. In a paper by Seeley et al. (2006) they found that early fromtotemporal dementia resulted in a 74% loss of Von Economo neurons throughout the cingulate and insula. VENs that remained were dysmorphic and plagued with tau protein accumulation. Other neuron types were unaffected and a control group of Alzheimers patients did not show the same pattern of VEN loss.

What remains unknown is where the Von Economo neurons project to and what function(s) they support. Everybody likes to do some hand-waving in this regard. Some argue that VENs are projecting to frontopolar cortex, while others believe that VENs in the cingulate and insula are reciprocally connected. This anatomical uncertainty hasn’t stopped scientists from hypothesizing that these cells may (or may not) be linked to high-speed intuitive decision making and possibly higher-order social cognition. From my perspective there is still little support for this case and extrapolating region-level fMRI results to the function of a single cell type is going too far.

In summary I find Von Economo neurons very fascinating. Part of what draws me to cognitive neuroscience is the philosophical investigation into what processes make humans so unique compared to other animals. I do believe that the VENs are one part of this greater puzzle. I also want to believe that VENs play a role in intuitive thought and higher-order processes. However, I fear it will be some time before scientists are able to adequately demonstrate that link.

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References and further reading:

The Allman Lab website

Allman JM, Hakeem AY, and Watson KK. (2002) “Two Phylogenetic Specializations in the Human Brain.” The Neuroscientist, 8(4): 35-346.

Allman JM, Watson KK, Tetreault NA, and Hakeen AY. (2005). “Intuition and autism: a possible role for Von Economo neurons.” Trends in Cognitive Sciences. 9(8): 367-373.

Seeley WW, Carlin DA, Allman JM, Macedo MN, Bush C, Miller BL, Dearmond SJ. (2006). “Early frontotemporal dementia targets neurons unique to apes and humans.” Annals of Neurology. 60(6): 660-667.

Von Economo C, and Koskinas. (1925). “Die Cytoarchtectonik der Hirnrinde des erwachsenen Menschen.”

September 7, 2007 • Posted in: CogNeuro, Emotion

5 Responses to “Brain Camp Review – Von Economo Neurons”

  1. Larry Leach - April 2nd, 2008

    This is interesting but how extensively have mammalian species been investigated to rule out their existence? Have they compared social vs. non-social species?

  2. Joe Erwin - July 10th, 2008

    Larry, your point is a good one. First, these neurons were thought to exist exclusively in humans. When Patrick Hof and Esther Nimchinsky found them in the in all the great apes, they reported having checked about 30 primate and 30 nonprimate mammal species without finding them (see Nimchinsky et al. PNAS, 1999). But eventually Hof and colleagues checked cetaceans, and found VENs in toothed but not baleen whales. Hof’s group and Allman’s group checked elephants, Asian and African, respectively, and found VENs in them. Much remains to be done, no doubt. All this is a lesson of some sort in scientific epistemology….

  3. karen dahn - October 28th, 2009

    I am interested in how VENS affect autism. How are they different than mirror neurons? Do autistic people have fewer VENS or are they somehow different or flawed? What about inflammation? Any ways of helping the autistic person function better? Any meds or therapies? I would appreciate any insights.

    Right now there is a lot of uncertainty regarding whether Von Economo neurons play a role in Autism. Allman et al. (2005) argued that there was a link between VENS and the social dysfunction observed in Autism. The article was mostly speculation, arguing that there may be a link for two reasons. First, VENS mature late in development relative to other cell types, roughly in step with traits of Autism that emerge during the first few years of life. Second, children with Autism are known to have structural and functional deficits in the anterior cingulate and fronto-insular cortex. These are the two regions of the brain where the greatest number of VENS are found. While these associations are intriguing, the Allman paper did not have much in the way of data to back up their hypotheses.

    Kennedy et al. (2007) conducted an experiment to explicitly examine the number of VENS in the fronto-insular cortex of individuals with Autism. Their results speak against the VENS hypothesis of Autism, as an equivalent number of neurons were found between Autistics and normal controls. This does not mean that the neurons were functioning in an equivalent manner, but does show that the cells are present and accounted for in fronto-insular cortex.

    Unfortunately a great deal more research is necessary before any medications or therapies can potentially be generated. We don’t even have a good grasp of how VENS function normally, let alone how to characterize their dysfunction in clinical disorders. There is an army of scientists working on the problem, but it is time-consuming, painstaking work. This is frustrating for us as researchers and doubly frustrating for the loved ones of Autistic individuals. Still, work is progressing – one day we may yet beat Autism. ~ Craig [Prefrontal]

  4. Robin P Clarke - January 22nd, 2010

    Craig, In your reply to Karen Dahn I wonder if you underrate the case for von Economo too much. Especially this sentence seems over the top:
    “The article was mostly speculation, arguing that there may be a link for two reasons.”

    Allman et al 2005 gave four citations in respect of the direct links to autism alone. They tied together a whole lot more dots into a coherent conception.

    The question of whether there are reduced VENS in autistic FI is not crucial to the confirmation of their thesis. They could be there but dysfunctioning, and they presented evidence suggestive of that.

    I don’t have enough close expertise to say with confidence that the case is a decisive yes, but it looks to me something that can’t reasonably be rated as mostly speculation. My own sensing (my von Economoes I guess) is that they are most probably on to something here. Lots of sound ideas in history have been held back with the S-word for too long.

  5. autism - March 2nd, 2011

    Craig, The paper by Kennedy et al. (2007) may have concluded that quantitatively the number of VENS is the same between individuals with autism and without, but other processes could still account for an impairment of function of the spindle cells or the way they establish connections with other neurons.

    I agree that this is very interesting research and I hope that someday will find out why individuals with autism have impairments in their higher-order social, emotional and behavioral functioning. Like others have mentioned, inflammatory processes (even those caused by gluten sensitivity in the gut) could very well influence the development of these Von Economo neurons.

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