Von Economo Neurons in the Human Medial Frontopolar Cortex

Abstract

The von Economo neurons (VEN) are characterized by a large soma, spindle-like soma, with little dendritic arborization at both, the basal and apical poles. In humans, VENs have been described in the entorhinal cortex, the hippocampal formation, the anterior cingulate cortex, the rostral portion of the insula and the dorsomedial Brodmann’s area 9 (BA9). These cortical regions have been associated with cognitive functions such as social interactions, intuition and emotional processing. Previous studies that searched for the presence of these cells in the lateral frontal poles yielded negative results. The presence of VENs in other cortical areas on the medial surface of the human prefrontal cortex which share both a common functional network and similar laminar organization, led us to examine its presence in the medial portion of the frontal pole. In the present study, we used tissue samples from five postmortem subjects taken from the polar portion of BA10, on the medial surface of both hemispheres. We found VENs in the human medial BA10, although they are very scarce and dispersed. We also observed crests and walls of the gyrus to quantitatively assess: (A) interhemispheric asymmetries, (B) the VENs/pyramidal ratio, (C) the area of the soma of VENs and (D) the difference in soma area between VENs and pyramidal and fusiform cells. We found that VENs are at least seven times more abundant on the right hemisphere and at least 2.5 times more abundant in the crest than in the walls of the gyrus. The soma size of VENs in the medial frontopolar cortex is larger than that of pyramidal and fusiform cells of layer VI, and their size is larger in the walls than in the crests. Our finding might be a contribution to the understanding of the role of these neurons in the functional networks in which all the areas in which they have been found are linked. However, the particularities of VENs in the frontal pole, as their size and quantity, may also lead us to interpret the findings in the light of other positions such as van Essen’s theory of tension-based brain morphogenesis.

Von Economo neurons are part of a larger neuronal population that are selectively vulnerable in C9orf72 frontotemporal dementia

“…This indicates that the loss and sparing of these neuronal types in dementia occurs concurrently, and supports the hypothesis that VENs and GABRQ‐expressing neurons are related and together form a larger cortical population . Additionally, the sparse expression of GABRQ in pyramidal neurons in layer 5 in the frontal and temporal cortex is in line with the recent uncovering of sparse VENs seen in the frontal cortex . It is possible that the GABRQ‐expressing neuronal population also includes a small number of neurons outside the ACC and FI.…”

Dendritic and Spine Heterogeneity of von Economo Neurons in the Human Cingulate Cortex

“…VENs would be a subpopulation of pyramidal neurons or "modified pyramidal neurons" (MPN) (Nimchinsky et al, 1995;González-Acosta et al, 2018). Braak (1979) considered layer Vb "slender pyramids or spindles" as MPN in the class of primitively organized Betz-cells in the anterogenual region of the human telencephalon.…”

Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons

“…VENs have been described in several large-brained mammals, such as humans, great apes, macaques, cetaceans, cows, and elephants, but not in rodents 4,5,6,7,8,9,10,1,11 . In humans, they are restricted to the anterior cingulate (ACC), frontoinsular (FI), and medial frontopolar regions of cerebral cortex 12 , while in most other species they are also found in the frontal and occipital poles 13 and may not be restricted to layer 5. Fork cells, another distinctive morphological-defined neuron type, are often found in the same brain regions as VENs and are similarly characterized by a single large basal dendrite, but differ from VENs by having a divided apical dendrite 1,14 .…”