The insular cortex, or “Island of Reil”, is hidden deep within the lateral sulcus of the brain. Subdivisions within the insula have been identified on the basis of cytoarchitectonics, sulcal landmarks, and connectivity. Depending on the parcellation technique employed, the insula can be divided into anywhere between 2 and 13 distinct subdivisions. The insula subserves a wide variety of functions in humans ranging from sensory and affective processing to high-level cognition. Here we provide a concise summary of known structural and functional features of the human insular cortex with a focus on lesion case studies and recent neuroimaging evidence for considerable functional heterogeneity of this brain region.

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.

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.

The main objective of this structural magnetic resonance imaging (MRI) study was to investigate, using diffusion tensor imaging, whether a neurofeedback training (NFT) protocol designed to improve sustained attention might induce structural changes in white matter (WM) pathways, purportedly implicated in this cognitive ability. Another goal was to examine whether gray matter (GM) volume (GMV) might be altered following NFT in frontal and parietal cortical areas connected by these WM fiber pathways. Healthy university students were randomly assigned to an experimental group (EXP), a sham group, or a control group. Participants in the EXP group were trained to enhance the amplitude of their β1 waves at F4 and P4. Measures of attentional performance and MRI data were acquired one week before (Time 1) and one week after (Time 2) NFT. Higher scores on visual and auditory sustained attention were noted in the EXP group at Time 2 (relative to Time 1). As for structural MRI data, increased fractional anisotropy was measured in WM pathways implicated in sustained attention, and GMV increases were detected in cerebral structures involved in this type of attention. After 50 years of research in the field of neurofeedback, our study constitutes the first empirical demonstration that NFT can lead to microstructural changes in white and gray matter.

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BackgroundIn temporal lobe epilepsy (TLE), advanced neuroimaging techniques reveal anomalies extending beyond the temporal lobe such as thinning of fronto-central cortices. Operculo-insular epilepsy (OIE) is an under-recognized and poorly characterized condition with the potential of mimicking TLE. In this work, we investigated insular and extra-insular cortical thickness (CT) changes in OIE.MethodsAll participants (14 patients with refractory OIE, 9 age- and sex-matched patients with refractory TLE and 26 healthy controls) underwent a T1-weighted acquisition on a 3 T MRI. Anatomical images were processed with Advanced Normalization Tools. Between-group analysis of CT was performed using a two-sided t-test (threshold of p < 0.05 after correction for multiple comparisons; cut-off threshold of 250 voxels) between (i) patients with OIE vs TLE, and (ii) patients with OIE vs healthy controls.ResultsSignificant widespread thinning was observed in OIE patients as compared with healthy controls mainly in the ipsilateral insula, peri-rolandic region, orbito-frontal area, mesiotemporal structures and lateral temporal neocortex. Contralateral cortical shrinkage followed a similar albeit milder and less diffuse pattern.The CT of OIE patients was equal or reduced relative to the TLE group for every cortical region analyzed. Thinning was observed diffusely in OIE patients, predominantly inboth insulae and the ipsilateral occipito-temporal area.ConclusionOur results reveal structural anomalies extending beyond the operculo-insular area in OIE.

Operculo-insular epilepsy (OIE) is an under-recognized condition that can mimic temporal and extratemporal epilepsies. Previous studies have revealed structural connectivity changes in the epileptic network of focal epilepsy. However, most reports use the debated streamline-count to quantify ‘connectivity strength’ and rely on standard tracking algorithms. We propose a sophisticated cutting-edge method that is robust to crossing fibers, optimizes cortical coverage, and assigns an accurate microstructure-reflecting quantitative conectivity marker, namely the COMMIT (Convex Optimization Modeling for Microstructure Informed Tractography)-weight. Using our pipeline, we report the connectivity alterations in OIE. COMMIT-weighted matrices were created in all participants (nine patients with OIE, eight patients with temporal lobe epilepsy (TLE), and 22 healthy controls (HC)). In the OIE group, widespread increases in ‘connectivity strength’ were observed bilaterally. In OIE patients, ‘hyperconnections’ were observed between the insula and the pregenual cingulate gyrus (OIE group vs. HC group) and between insular subregions (OIE vs. TLE). Graph theoretic analyses revealed higher connectivity within insular subregions of OIE patients (OIE vs. TLE). We reveal, for the first time, the structural connectivity distribution in OIE. The observed pattern of connectivity in OIE likely reflects a diffuse epileptic network incorporating insular-connected regions and may represent a structural signature and diagnostic biomarker.

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