Von Economo neurons: A Review of the Anatomy and Functions

Abstract

Von Economo neurons (VENs) are large bipolar neurons found in the
anterior cingulate, frontoinsular and dorso-lateral prefrontal cortices of great
apes and the humans. VENs are defined by their thin, elongated cell body
and long dendrites projecting from the apical and basal ends. These neurons
are mostly present in particularly high densities in cetaceans, elephants, and
hominoid primates mainly, humans and apes. VENs have been shown to
contribute in the specializations of neural circuits in species that share both
large brain size and complex social cognition due to their location. This could
possibly be due to the adaptation to rapidly relay of socially-relevant information
over long distances across the brain. The VENs have been shown to be recently
evolved cell type which may be involved in the fast intuitive assessment of
complex social situations. As such, they could be part of the circuitry supporting
human social networks. The VENs emerge mainly after birth and increase in
number until four years of age. The presence of VENs in the frontoinsular cortex
has been linked to a possible role in the integration of bodily feelings, emotional
regulation and goal-directed behaviors. Some studies have shown decreased
number of VENs in neuropsychiatric diseases in which social cognition is
markedly affected. Some researchers have shown that selective destruction
of VENs in the early stages of frontotemporal dementia implies that they are
involved in empathy, social awareness, and self-control which is consistent with
evidence from functional imaging.
Keywords: Von Economo Neurons; Humans; Apes; Frontoinsular cortex;
Prefrontal Cortex; Frontotemporal dementia

Full text

Citation: Ibegbu AO, Umana UE, Hamman WO and Adamu AS. Von Economo neurons: A Review of the
Anatomy and Functions. Austin J Anat. 2014;1(5): 1026.
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ISSN : 2381-8921 | www.austinpublishinggroup.com
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Open Access
Abstract
Von Economo neurons (VENs) are large bipolar neurons found in the
anterior cingulate, frontoinsular and dorso-lateral prefrontal cortices of great
apes and the humans. VENs are dened by their thin, elongated cell body
and long dendrites projecting from the apical and basal ends. These neurons
are mostly present in particularly high densities in cetaceans, elephants, and
hominoid primates mainly, humans and apes. VENs have been shown to
contribute in the specializations of neural circuits in species that share both
large brain size and complex social cognition due to their location. This could
possibly be due to the adaptation to rapidly relay of socially-relevant information
over long distances across the brain. The VENs have been shown to be recently
evolved cell type which may be involved in the fast intuitive assessment of
complex social situations. As such, they could be part of the circuitry supporting
human social networks. The VENs emerge mainly after birth and increase in
number until four years of age. The presence of VENs in the frontoinsular cortex
has been linked to a possible role in the integration of bodily feelings, emotional
regulation and goal-directed behaviors. Some studies have shown decreased
number of VENs in neuropsychiatric diseases in which social cognition is
markedly affected. Some researchers have shown that selective destruction
of VENs in the early stages of frontotemporal dementia implies that they are
involved in empathy, social awareness, and self-control which is consistent with
evidence from functional imaging.
Keywords: Von Economo Neurons; Humans; Apes; Frontoinsular cortex;
Prefrontal Cortex; Frontotemporal dementia
social cognition, possibly representing an adaptation to rapidly relay
socially-relevant information over long distances across the brain [13].
Recent evidence indicates that unique patterns of protein expression
may also characterize VENs, particularly involving molecules that are
known to regulate gut and immune function [13,14].
VENs are a recently evolved cell type which may be involved in
the fast intuitive assessment of complex situations. As such, they could
be part of the circuitry supporting human social networks [11,14].
It has been shown that VENs relay an output of fronto-insular and
anterior cingulate cortex to the parts of frontal and temporal cortex
associated with theory-of-mind, where fast intuitions are melded
with slower, deliberative judgments [8,15]. VENs emerge mainly
aer birth and increase in number until the age of four years of age
and that in autism spectrum disorders VENs fail to develop normally
[16,17]. is failure might be partially responsible for the associated
social disabilities that result from faulty intuition in autistic people.
e presence of VENs in the frontoinsular cortex has been linked to a
possible role in the integration of bodily feelings, emotional regulation,
and goal-directed behaviors [7,12]. ey have also been implicated
in fast intuitive evaluation of complex social situations. Studies have
reported a decreased number of VENs in neuropsychiatric diseases in
which the dimension of social cognition is markedly aected [7,16].
The Structure and Anatomy of Economo
Neurons
VENs are large, bipolar neurons with one large apical axon and
Introduction
Von Economo neurons (VENs) are bipolar neurons found in the
anterior cingulate, frontoinsular, and dorso-lateral prefrontal cortices
of great apes which include humans, gorillas, chimpanzees, bonobos
and orangutans [1,2]. ese neurons, also called Spindle neurons
are characterized by a large spindle-shaped cell body or soma with a
tapering single apical axon in one direction. Whereas other types of
neurons tend to have many dendrites, the polar shaped morphology
of spindle neurons is unique [3,4]. ese group of neurons were
previously thought to be unique to the great apes but have more
recently been found in cetaceans such as the humpback, n, killer and
sperm whales [5,6,7]. Because of their morphology and anatomical
location, it has been speculated that VENs may play important role
in intuitive choice in social situations and that their dysfunction may
be a factor in autism and Alzheimer’s disease [8,9]. VENs were rst
described by Constantin Von Economo in 1925, and their exclusivity
to the great apes was discovered in 1999 by Allman and colleagues
[1,10].
VENs are dened by their thin, elongated cell body and long
dendrites projecting from the apical and basal ends [11]. ese
distinctive neurons are mostly present in anterior cingulate and
fronto-insular cortex, with particularly high densities in cetaceans,
elephants and hominoid primates mainly humans and apes [8,12].
is distribution suggests that VENs contribute to specializations of
neural circuits in species that share both large brain size and complex
Review Article
Von Economo neurons: A Review of the Anatomy and
Functions
Ibegbu AO*, Umana UE, Hamman WO and
Adamu AS
Department of Human Anatomy, Ahmadu Bello
University Zaria, Kaduna State Nigeria
*Corresponding author: Dr. A.O. Ibegbu, Department
of Human Anatomy, Faculty of Medicine, Ahmadu
Bello University Zaria, Kaduna State Nigeria, 8100, Tel:
+2348032188042; Email: aoibegbu@yahoo.com
Received: October 28, 2014; Accepted: November 05,
2014; Published: November 10, 2014

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a single basal dendrite. ey are found exclusively in layer Vb of
the anterior cingulate cortex (ACC) and fronto-insular cortex (FI)
as shown in Figures 1 and 2, and have been identied in human
dorso-lateral prefrontal cortex (DLPFC), Brodmann area [3,18]. Its
large apical axon and high-volume, elongated soma is similar to that
of the cortical pyramidal neuron, but the VEN lacks the pyramidal
neuron’s numerous basal dendrites, instead receiving inputs from
a comparatively small subset of cortex; the average VEN is about
5 times larger than the average layer 5 pyramidal cells as shown in
Figures 3 and 5 [5,8]. eir structural similarity to pyramidal neurons
suggests that VENs may play a similar functional role, and because
the speed at which neurons conduct information typically co-varies
with the diameter of their axon, the large VENs may do so very
quickly compared to other neurons as in Figure 3 [2,7]. VENs are
relatively rare, comprising 1-2% of the total neurons in layer 5 of
the ACC [4,19]. In FI, VENs are 30% more numerous in the right
hemisphere than the le a hempispherization that occurs in the rst
four years of postnatal development in humans [2,11].
Ontogeny and Phylogeny
Von Economo neurons (VENs) develop late both ontogenetically
and phylogenetically. Ontogenetically, VENs rst appear in the
35th week of gestation; at birth only about 15% of the post-natal
numbers are present, and at four years old, the adult numbers are
present [2,8]. Analyses of over 30 mammalian species have failed
to nd VENs except in primates and cetaceans. Among primates
including gibbons, VENs have only been found in the great apes,
humans, gorillas, chimpanzees, bonobos, and orangutans [11,20].
Among the great apes, humans have the most VENs, both in terms of
absolute number and relative percentage compared to total number
of neurons [10]. In decreasing order of total number, VENs are
found in humans, bonobos, chimpanzees, gorillas, and orangutans.
Unlike in the other species exhibiting them, VENs in humans and
bonobos are distributed in clusters of 3-6 neurons. In analyses of total
number of VENs present in FI of both hemispheres, the average adult
human was found to have 193,000 cells, a four year old human child
had 184,000, the average human newborn had 28,200, a gorilla had
16,710, a bonobo had 2,159, and a chimpanzee had 1,808 [19,20].
at their relative abundance and clustering in species co-varies with
a specie’s phylogenetic proximity to humans has led to speculation
that VENs are important to evolution and cognition [4,5]. at
they occur in hominids and pongids but no other primates suggests
that VENs evolved relatively recently approximately 15-20 million
years ago, prior to the evolutionary divergence of orangutans and
hominids [12,21]. eir discovery in some whales suggests a second,
independent evolution of VENs, though they may not have the same
function in both apes and cetaceans [21,22].
e observation that spindle neurons only occur in a highly
signicant group of animals has led to speculation that they are of
great importance in human evolution and/or brain function as in
Figures 2 and 4. eir restriction among the primates to great apes
leads to the hypothesis that they developed no earlier than 15-20
Figure 1: Regions of the brain containing Von Economo neurons (VENs).
(a) A lateral view of the brain, with fronto-insular cortex (FI) shown in red.
(b) A medial view of the brain, with anterior cingulate cortex (ACC) shown
in red [10].
Figure 2: Location of the frontoinsular cortex (FI) and anterior cingulate
cortex (ACC) on coronal brain sections [19,20].
Figure 3: Photomicrographs of soma and proximal dendrites of (a) a
pyramidal and (b) the VENs stained with the Golgi method [5].
Figure 4: Primate cladogram detailing the species examined for VENs.
Species in red have VENs in the FI. Pongids have VENs in the ACC only [1].

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million years ago, prior to the divergence of orangutans from the
African great apes. e discovery of spindle neurons in diverse
whale species [6], has led to the suggestion that they are a possible
obligatory neuronal adaptation in very large brains, permitting fast
information processing and transfer along highly specic projections
and that evolved in relation to emerging social behaviors [22]. eir
presence in the brains of these species supports the theory, pointing
towards the existence of these specialized neurons only in highly
intelligent mammals, and may be an example of convergent evolution
[6,23]. ough currently unknown where VENs ultimately project
to, ACC and FI connect to numerous anatomical areas: prefrontal,
orbito-frontal, insular and anterior temporal cortices, amygdala,
hypothalamus, and various thalamic nuclei. Allman and others have
speculated that VENs project information processed in FI and ACC
to other parts of the brain, including Brodmann’s area 10, in fronto-
polar cortex [24,25].
All of the primates had more spindle cells in the fronto-insula
of the right hemisphere than in the le. In contrast to the higher
number of spindle cells found in the ACC of the gracile bonobos
and chimpanzees, the number of fronto-insular spindle cells was far
higher in the cortex of robust gorillas but no data for Orangutans
was given [1,2]. An adult human had 82,855 such cells, a gorilla had
16,710, a bonobo had 2,159, and a chimpanzee had a mere 1,808 –
despite the fact that chimpanzees and bonobos are great apes most
closely related to humans [19,20].
Function and Behaviour
e FI and ACC, where VENs are located, are thought to be
implicated in social reasoning, empathy, emotion, and monitoring
of visceral autonomic activity, among other functions. ACC projects
to the fronto-polar cortex, which has been implicated in cognitive
dissonance and uncertainty [16]. Because their morphology suggests
them as fast-projection neurons, and because of the functions of
the areas they are thought to receive information from and project
information to, it is speculated that VENs have an important role to
play in intuition, which allows one to overcome uncertainty, make
quick decisions and resolve cognitive dissonance [2]. Allman and
Colleagues had reported that spindle neurons help channel neural
signals from deep within the cortex to relatively distant parts of
the brain [1]. ey found that signals from the ACC are received in
Brodmann’s area 10, in the frontal polar cortex, where regulation of
cognitive dissonance, disambiguation between alternatives is thought
to occur. According to Allman and Others [1,2], this neural relay
appears to convey motivation to act, and concerns the recognition
of error. Self-control and avoidance of error, is thus facilitated by
the executive gate-keeping function of the ACC, as it regulates the
interference patterns of neural signals between these two brain
regions.
In humans, intense emotion activates the anterior cingulate
cortex, as it relays neural signals transmitted from the amygdala, a
primary processing center for emotions to the frontal cortex, perhaps
by functioning as a sort of lens to focus the complex texture of neural
signal interference patterns. e ACC is also active during demanding
tasks requiring judgment and discrimination, and when errors are
detected by an individual. During dicult task or when experiencing
intense love, anger or lust, activation of the ACC is increased. In brain
imaging studies, the ACC has specically been found to be active
when mothers hear infants cry, underscoring its role in aording a
heightened degree of social sensitivity.
e ACC is a relatively ancient cortical region and is involved
with many autonomic functions, including motor and digestive
functions, while also playing a role in the regulation of blood pressure
and heart rate. Signicant olfactory and gustatory capabilities of
the ACC and fronto-insular cortex appear to have been usurped,
during evolution, to serve enhanced roles related to higher cognition,
ranging from planning and self awareness to role playing and
deception. e diminished olfactory function of humans, compared
to other primates, may be related to the fact that spindle cells located
at crucial neural network hubs have only two dendrites rather than
many, resulting in reduced neurological integration [5,19,21].
Abnormal spindle neuron development may be linked to several
psychotic disorders, typically those characterized by distortions
of reality, disturbances of thought, disturbances of language, and
withdrawal from social contact. Abnormal VEN development has
been implicated in autism [2], and selective degeneration of VENs
has been observed in Alzheimer’s and dementia [12]. Altered spindle
neurons have been implicated in both schizophrenia and autism, but
research into these correlations are at a very early stage. An initial
study suggested that Alzheimer’s disease specically targeted Von
Economo neurons however this study was performed with end-stage
Alzheimer brains in which cell destruction was widespread. Later,
it was found that Alzheimer’s disease doesn’t aect the VENS, but
behavioral variant fronto-temporal lobe degeneration specically
targets these cell populations in the anterior cingulate cortex and the
anterior insula early in the disease [12,18,25].
Conclusion
e von Economo neurons (VENs) are large bipolar neurons
located in the frontoinsular cortex (FI) and limbic anterior (LA) area
in great apes and humans but not in other primates. Stereological
counts of VENs in FI and LA show them to be more numerous in
humans than in apes. In humans, small numbers of VENs appear the
36th week postconception, with numbers increasing during the rst
8 months aer birth. ere are signicantly more VENs in the right
hemisphere in postnatal brains; this may be related to asymmetries
in the autonomic nervous system. VENs are also present in elephants
and whales and may be a specialization related to very large brain
size. e large size and simple dendritic structure of these projection
Figure 5: Von Economo neuron compared to Pyramidal neuron [5].

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neurons suggest that they rapidly send basic information from FI and
LA to other parts of the brain, while slower neighboring pyramids
send more detailed information. Selective destruction of VENs in
early stages of frontotemporal dementia (FTD) implies that they
are involved in empathy, social awareness, and self-control in which
VENs fail to develop normally in autism broad spectrum disorders
which may be responsible for the associated social disabilities
resulting from faulty intuition.
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Citation: Ibegbu AO, Umana UE, Hamman WO and Adamu AS. Von Economo neurons: A Review of the
Anatomy and Functions. Austin J Anat. 2014;1(5): 1026.
Austin J Anat - Volume 1 Issue 5 - 2014
ISSN : 2381-8921 | www.austinpublishinggroup.com
Ibegbu et al. © All rights are reserved