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Abstract

We examined the dynamic functional connectivity of the von Economo neuron (VEN) area of the anterior insula cortex (AIC) using two-shot echo-planar functional magnetic resonance imaging with direct electrical stimulation (DES-fMRI), seed-based connectivity analysis (SBCA), and local field potential recordings (NET-fMRI) in the anesthetized macaque monkey. The electrical stimulation (n=3) of the left or right VEN area activated several distinct subcortical limbic nuclei (e.g. amygdala, midline thalamic nucleus [MTN]) and high-order cortical areas (e.g. superior temporal sulcus, extrastriate visual areas). Both the left and the right stimulation produced a rather lateralized activation pattern, with the activation elicited from one side roughly mirroring the activation obtained from the other side. Nevertheless, stimulation of the left VEN area elicited a consistently more intense and broader bilateral activation. The correlation patterns obtained with a SBCA of the same data set, using the left and right VEN area as seeds, confirmed the activation patterns elicited by the electrical stimulation. Conversely, SBCA using spontaneous data sets, collected in the same animals without electrical stimulation, revealed not only a correlation between both VEN areas but also a broader bilateral correlation pattern that remained identical regardless of the seeded side. Whereas many limbic and cortical activations produced by the electrical stimulations were matched by a correlation with the spontaneous activity of the VEN areas, the MTN was neither correlated nor anticorrelated with the spontaneous activity. Finally, in the NET-fMRI with the same spontaneous functional scans, the occurrence of oscillatory events (e.g. alpha, theta, gamma) in the left or right VEN area triggered varying patterns of activity that differed from the electrical stimulation patterns while being nonetheless markedly asymmetric. Events from the left or right VEN area often correlated with respectively massive activation or deactivation patterns. The present study reveals that small individual regions of the brain can simultaneously display a broad diversity of functional connectivity patterns. The asymmetric activity patterns associated with the left and right VEN areas corroborate prior evidence for a left-right functional asymmetry in the AIC (Craig, 2005, Trends Cogn Sci). The spatially restricted or broad activation of limbic and high-order regions from the right and left VEN areas, respectively, might underlie the asymmetric role of the AIC in monitoring internal bodily states during cognitive processes, including subjective perceptual awareness.