The von Economo neurons in frontoinsular and anterior cingulate cortex in great apes and humans

Abstract

The von Economo neurons (VENs) are large bipolar neurons located in frontoinsular (FI) and anterior cingulate cortex in great apes and humans, but not other primates. We performed stereological counts of the VENs in FI and LA (limbic anterior, a component of anterior cingulate cortex) in great apes and in humans. The VENs are more numerous in humans than in apes, although one gorilla approached the lower end of the human range. We also examined the ontological development of the VENs in FI and LA in humans. The VENs first appear in small numbers in the 36th week post-conception, are rare at birth, and increase in number during the first 8 months after birth. There are significantly more VENs in the right hemisphere than in the left in FI and LA in postnatal brains of apes and humans. This asymmetry in VEN numbers may be related to asymmetries in the autonomic nervous system. The activity of the inferior anterior insula, which contains FI, is related to physiological changes in the body, decisionmaking, error recognition, and awareness. The VENs appear to be projection neurons, although their targets are unknown. We made a preliminary study of the connections of FI cortex based on diffusion tensor imaging in the brain of a gorilla. The VEN-containing regions connect to the frontal pole as well as to other parts of frontal and insular cortex, the septum, and the amygdala. It is likely that the VENs in FI are projecting to some or all of these structures and relaying information related to autonomic control, decision-making, or awareness. The VENs selectively express the bombesin peptides neuromedin B (NMB) and gastrin releasing peptide (GRP) which are also expressed in another population of closely related neurons, the fork cells. NMB and GRP signal satiety. The genes for NMB and GRP are expressed selectively in small populations of neurons in the insular cortex in mice. These populations may be related to the VEN and fork cells and may be involved in the regulation of appetite. The loss of these cells may be related to the loss of satiety signaling in patients with frontotemporal dementia who have damage to FI. The VENs and fork cells may be morphological specializations of an ancient population of neurons involved in the control of appetite present in the insular cortex in all mammals. We found that the protein encoded by the gene DISC1 (disrupted in schizophrenia) is preferentially expressed by the VENs. DISC1 has undergone rapid evolutionary change in the line leading to humans, and since it suppresses dendritic branching it may be involved in the distinctive VEN morphology.

The Williams syndrome chromosome 7q11.23 hemideletion confers hypersocial, anxious personality coupled with altered insula structure and function

“…Given the role of the uncinate fasciculus in relaying synaptic information between the frontoamygdalar system and the AI (26)(27)(28), this compromised amygdala-OFC white-matter connectivity via the AI, along with our findings of negative functional rCBF coupling of right vAI with OFC and dorsal insular subregions, provides direct anatomical and functional support for previous findings of disrupted functional fronto-amygdala connectivity in WS during processing of emotions (17,28). These results are consistent with neuroanatomical evidence suggesting marked rightward asymmetry of this system in normal subjects (35,42). Thus, the enlarged vAI on the right side and the preservation of normal FA in the right uncinate fasciculus in WS may be related to the prevalence of von Economo neurons in the right AI (35) and a preponderance of uncinate fasciculus volume and fiber numbers on the right side in normal subjects (42).…”

“…Of relevance to the altered fronto-amygdalar responses and connectivity during affect processing in WS (12,17,28,30), the insula is anatomically interconnected with subregions of the amygdala, OFC, and ACC (32)(33)(34). Moreover, the AI is cytoarchitectonically characterized by marked abundance of von Economo neurons (35), which are also selectively present elsewhere in the so-called "salience network" (36), including the OFC and ACC, of humans and nonhuman primates (37); these neurons may play an important role in regulating executive control relevant for emotional awareness (4,35,37,38). These findings, together with reports of structural perturbations of the AI (39), suggest that the human insula, especially the AI, is a neural target through which the genetically determined atypical empathy, nonsocial anxiety, and hypersocial WS personality (12)(13)(14)(15)29) may be mediated.…”

The evolution of brains from early mammals to humans

“…Thus, there is a posterior granular region followed by more anterior dysgranular and agranular regions [79]. A most rostral region of the insula is distinguished in humans and apes by the presence of an unusual type of neuron, the von Economo or spindle shaped neurons, which are more common in the right than the left insula [80]. The human insula is amazing in absolute size.…”

Efficacy of memantine on neuropsychiatric symptoms associated with the severity of behavioral variant frontotemporal dementia: A six-month, open-label, self-controlled clinical trial

“…Neuropathological and imaging studies of early FTLD suggest that the disease begins in the anterior cingulate cortex (ACC) and frontoinsula (FI) before spreading throughout a circumscribed network of brain regions (35,36). ACC and FI are the exclusive location of the von Economo neuron (VEN) that is specifically and selectively attacked in the early stages of bvFTD; these are implicated in several neuropsychiatric illnesses, in particular in disturbances of empathy, social awareness and self-control (37,38). In addition, the VEN somatodendritic compartment appears to primarily express dopamine (D3), serotonin (5HT-1b, 2b) and vasopressin (1a) receptors, but does not respond to glutamic acid (39).…”