Elemental localization of the von Economo neuron in the macaque monkey insula

We recently demonstrated that the von Economo neuron (VEN) and its companion, the fork neuron (FN), occur in the anterior insular cortex (AIC) in the macaque monkey (Evrard et al., 2012 Neuron74:482-9). In a separate study of the overall organization of the insula, we also showed that the insula is divided into several distinct small and sharply-delimited cytoarchitectonic areas (Evrard et al., 2014 J Comp Neurol 522:64-97). Here, we use high- and low-magnification microscopy in both cynomolgus and rhesus macaque monkeys to investigate the exact localization of the VEN and FN with regards to the architectonic borders of the AIC. Using independent examinations of the VEN/FN distributions and AIC architecture, we showed that both cells specifically occur in one architectonic area, the “lateral agranular area of the insula” (or Ial). The sharpness of the delimitation of the VEN allowed to predict the localization of the Ial borders when plotting the VEN at high microscope magnification and, likewise, to predict the localization of the VEN when searching for the borders of Ial at low stereoscope magnification. This type of specific areal localization corresponds to what Brodmann called an "elemental" localization, which he described at the time for the Betz cell of the motor cortex and the Meynert cell of the visual system. In light of recent developments in the study of cortical development and areal specificity, this elemental localization could offer us a unique anatomical leverage for the examination of the development, connections and functions of the VEN and FN in macaques. In addition to the anterior group of VEN and FN, we showed for the first time that a second, distinct cluster of VEN occurs further posteriorly in the insula, in particular within the borders of a small architectonic module of the mound dysgranular area of the insula” (or Idm). This new cluster, if confirmed in humans, would offer a second point of homologous anchorage between humans and macaque monkeys