Von Economo (Spindle) Cells Number and Size

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Human Uniqueness Compared to "Great Apes": 
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Von Economo neurons (also known as spindle cells) are more abundant and larger in humans than in great apes. The von Economo neurons (VENs) are large bipolar projection neurons located exclusively in layer V of the anterior cingulate cortex (ACC) and frontoinsular cortex (FI) that were originally described in humans by Constantin von Economo and were later observed in all great apes as well. VENs are more abundant and larger in humans than in great apes, and are also larger than neighboring pyramidal neurons and fusiform cells. VENs are absent in all other primates that have been examined, however, including gibbons, Old World monkeys, New World monkeys, and prosimians. Besides hominids, VENs have been recently observed with a similar regional distribution in the brains of many cetacean species, and in elephants. VENs are known to project outside of the cerebral cortex and are thought to be part of neural networks subserving some of the higher cognitive functions in which the ACC and FI are involved in, such as judgment, attention, intuition, and social awareness, as well as regulation of homeostasis. In humans, VENs have been shown to be dramatically affected by degenerative changes in patients with frontotemporal dementia, a disorder characterized by loss of affect and expressiveness, dissolution of judgment, and blunted emotionality. In this context, it is possible that VENs represent a possible obligatory neuronal adaptation in species with the largest brains and body sizes in their respective orders, permitting fast information processing and transfer along highly specific projections and that convergently evolved in relation to emerging social behaviors in select groups of mammals.









Timing of appearance of the difference in the Hominin Lineage as a defined date or a lineage separation event. The point in time associated with lineage separation events may change in the future as the scientific community agrees upon better time estimates. Lineage separation events are defined in 2017 as:

  • the Last Common Ancestor (LCA) of humans and old world monkeys was 25,000 - 30,000 thousand (25 - 30 million) years ago
  • the Last Common Ancestor (LCA) of humans and chimpanzees was 6,000 - 8,000 thousand (6 - 8 million) years ago
  • the emergence of the genus Homo was 2,000 thousand (2 million) years ago
  • the Last Common Ancestor (LCA) of humans and neanderthals was 500 thousand years ago
  • the common ancestor of modern humans was 100 - 300 thousand years ago

Possible Appearance: 
6,000 thousand years ago
Definite Appearance: 
100 thousand years ago
Background Information: 

 Von Economo neurons (also known as spindle cells) are more abundant and larger in humans than in great apes. The von Economo neurons (VENs) are large bipolar projection neurons located exclusively in layer V of the anterior cingulate cortex (ACC) and frontoinsular cortex (FI) that were originally described in humans by Constantin von Economo and were later observed in all great apes as well.

The Human Difference: 

 The human differ markedly from other hominids in terms of VEN numbers and individual volumes. In both FI and ACC, adult humans have strikingly higher numbers of VENs. They are less numerous in FI than in ACC, accounting for about 50-60% of the numbers observed in ACC. Hemispheric VEN numbers average 73,000 in the adult human FI and 160,000 in the ACC. There does not appear to be clear gender differences in these numbers. Relative to the total number of neurons in these regions, VENs represent a very small population accounting for about 1% of all neurons. Chimpanzees and gorillas have much lower numbers of VENs, usually a few thousands based on still limited current estimates. VENs are very rare in orangutans. Human VENs are also much larger than in great apes, and than neighboring pyramidal neurons. In human ACC, VEN volumes average 21,000 µm3 compared to mean values ranging from 5,500 to 8,800 µm3 in great apes. In contrast, ACC pyramidal neurons have volumes ranging on average from 1,900 µm3 in orangutans to 4,500 µm3 in humans. VENs local distribution tends to form little clusters in layer V, a characteristic most notable in chimpanzees and human.

Universality in Human Populations: 

 As far as we can infer from available postmortem brain materials these neurons are present in all modern human populations.

Mechanisms Responsible for the Difference: 

 The ACC and FI can be envisioned as limbic motor and sensory cortical fields, respectively. Their role in cortical control of autonomic functions, such as heart rate, blood pressure, and digestive functions, is well conserved. ACC in macaques is interconnected with the amygdala and has been shown to have layer V projections to the hypothalamus and the periaqueductal gray as well. As such, VENs in ACC (and in FI as well, although the connectivity of FI cannot be inferred directly from macaque monkey studies) might represent a population of specialized neurons integrating inputs with emotional overtones and project to highly specific motor centers controlling vocalization, facial expression, or regulation of visceral, olfactory, and gustatory functions, as well as complex alimentary behaviors. VENs may also be involved in higher-level processes in prefrontal cortex networks that are responsible for more than certain aspects of sensory input or motor output, such as attention, moral judgment, self-recognition, empathy, communication, and social awareness. In this context, the unique correlation, among the resident neurons of layers V and VI, of the cellular volume of VENs with encephalization in human and great apes lends further support to the possible association of spindle cells with higher cortical functioning. It is also worth noting that the emergence of VENs coincides with the evolution of the planum temporale, a region that is important for language comprehension. Considering the language comprehension abilities of great apes, it is possible that several cortical structures involved in the production of specific vocalizations and in communicative and social skills sustained simultaneous, considerable, adaptive modifications during brain evolution in hominids.

Implications for Understanding Modern Humans: 

 VENs in hominids can be envisioned as a window disclosing the progressive shaping of a complex neuronal system during the evolution of a crown group of primates. Because of the species in which these neurons occur are not tractable to cell-specific, invasive experimental paradigms, their precise function and connectivity has remained elusive. Insight can be however gained from the study of neurologic and psychiatric conditions affecting the human brain selectively. Whereas VENs are not affected in Alzheimer’s disease until late, very severe stages of dementia, they were found to be extremely vulnerable early on during the progression of frontotemporal dementia, showing accumulation of degenerative changes resulting in a ca. 75% loss. Interestingly, patients with frontotemporal dementia show dissolution of their social skills, communication capabilities, emotionality, empathy, and judgment, as cardinal symptoms of disease progression, relating well the selective vulnerability of VENs to particular aspects of cognitive function, generally associated to the integrity of prefrontal networks. Patients with agenesis of the corpus callosum, a congenital disorder resulting in a partial or total absence of the corpus callosum and characterized by significant deficits in social and emotional behaviors, exhibit reduced numbers of VENs by as much as 50% in ACC and FI, suggesting that VEN loss may be related to the specific genetic abnormality that caused callosal agenesis. Most patients with schizophrenia show alterations in VEN morphology and laminar distribution, indicating possible abnormalities in their development, although definite data on VEN numbers remain to be generated. Finally, some patients with autism appear to have disrupted distribution of VENs, with atypical localization to other cortical regions, as well as reduction in their local densities, probably varying in function of impairment severity and precise diagnostic categorization within autism spectrum disorders. Data from these neurodevelopmental disorders are to date highly variable among the few available (and limited) studies and much work is needed to clarify the fate of VENs in such cases. Altogether, these clinicopathologic data favor a role of VENs in higher cognitive process and complex behaviors involving a sense of self and relation to others, social communication, expression and control of emotions, and regulation of homeostasis. Further analyses, particularly using proteomics and transcriptomics approaches, are clearly necessary to understand better the factors that render VENs susceptible to degeneration or developmental abnormalities in humans.

Occurrence in Other Animals: 

 VENs were rediscovered in hominids following their original description by Von Economo, and at the time were thought to occur only in human and great apes to the exclusion of all other primates and mammals. More recently, they have been observed in considerable numbers in the ACC, anterior insula (including FI) of many cetaceans, as well as in elephants. In addition to these regions, VENs occur in substantial numbers in the frontopolar cortex of the humpback whale (interestingly rare VENs can be found in the human dorsolateral frontal cortex, suggesting possible regional homologies between the two Orders). It appears that mysticetes have much more VENs than smaller odontocetes (about 24,000 in the ACC compared to 1,800). The number of VENs relative to the total number of neurons in these cortical regions is indeed lower than in hominids, accounting for only 0.06 at most of the total number of neurons. Interestingly, the African elephant has about 19,000 VENs in FI, which is comparable than the value obtained in the humpback whale anterior insula/FI (28,000). In cetaceans, VENs are also larger than pyramidal neurons and attain volumes comparable to those observed in great apes (~4,000-7,000 µm3). It is worth noting that VENs occur in a comparable regional distribution in species that are all known for their large brain size, large body size, and generally high encephalization quotient, and that display highly developed social behaviors, self-recognition, and communication skills. In addition to supporting homology of cortical regions and function among unrelated lineages of mammals, VENs present a remarkable case of convergent evolution in the context of the progressive differentiation of distinct neuronal systems that appeared first in the ancestor of modern cetaceans (~35 MYA), then in the ancestor of hominids (~16 MYA), and again in recent elephantids (~8 MYA).


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