The insula is a complex structure involved in a wide range of functions. Tracing studies on nonhuman primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state-of-the-art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing an HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro-caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions.

See Jackson (doi:) for a scientific commentary on this article.The neural substrate of Gilles de la Tourette syndrome is unknown. Worbe et al. use probabilistic tractography to demonstrate widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways—likely arising from abnormal brain development—in patients with this syndrome.

Hidden beneath the Sylvian fissure and sometimes considered as the fifth lobe of the brain, the insula plays a multi-modal role from its strategic location. Previous structural studies have reported cortico-cortical connections with the frontal, temporal, parietal and occipital lobes, but only a few have looked at its connections with subcortical structures. The insular cortex plays a role in a wide range of functions including processing of visceral and somatosensory inputs, olfaction, audition, language, motivation, craving, addiction and emotions such as pain, empathy and disgust. These functions implicate numerous subcortical structures, as suggested by various functional studies. Based on these premises, we explored the structural connectivity of insular ROIs with the thalamus, amygdala, hippocampus, putamen, globus pallidus, caudate nucleus and nucleus accumbens. More precisely, we were interested in unraveling the specific areas of the insula connected to these subcortical structures. By using state-of-the-art HARDI tractography algorithm, we explored here the subcortical connectivity of the insula.

In early AD, augmented CSF sTREM2 levels correspond with cerebral MRI features typical of brain swelling, supporting a role for TREM2 in the regulation of the neuroinflammatory response to early neurodegeneration.