Increased network centrality of the anterior insula in early abstinence from alcohol

Abnormal resting-state functional connectivity, as measured by functional magnetic resonance imaging (MRI), has been reported in alcohol use disorders (AUD), but findings are so far inconsistent. Here, we exploited recent developments in graph-theoretical analyses, enabling improved resolution and fine-grained representation of brain networks, to investigate functional connectivity in 35 recently detoxified alcohol dependent patients versus 34 healthy controls. Specifically, we focused on the modular organization, that is, the presence of tightly connected substructures within a network, and on the identification of brain regions responsible for network integration using an unbiased approach based on a large-scale network composed of more than 600 a priori defined nodes. We found significant reductions in global connectivity and region-specific disruption in the network topology in patients compared with controls. Specifically, the basal brain and the insular-supramarginal cortices, which form tightly coupled modules in healthy subjects, were fragmented in patients. Further, patients showed a strong increase in the centrality of the anterior insula, which exhibited stronger connectivity to distal cortical regions and weaker connectivity to the posterior insula. Anterior insula centrality, a measure of the integrative role of a region, was significantly associated with increased risk of relapse. Exploratory analysis suggests partial recovery of modular structure and insular connectivity in patients after 2 weeks. These findings support the hypothesis that, at least during the early stages of abstinence, the anterior insula may drive exaggerated integration of interoceptive states in AUD patients with possible consequences for decision making and emotional states and that functional connectivity is dynamically changing during treatment.This work was supported by the European Union's Horizon 2020 research and innovation programme (668863-SyBil-AA), the ERA-Net NEURON programme (FKZ 01EW1112-TRANSALC) and Deutsche Forschungsgemeinschaft (center grants SFB636 and TRR 265 subproject B0867). SC acknowledges the Spanish State Research Agency through the Severo Ochoa Programme for Centres of Excellence in R&D (SEV-2017-0723) and the Ministerio de Economía y Competitividad (MINECO) and FEDER funds under grants BFU2015-64380-C2-1-R and BFU2015-64380-C2-2-R.Open Access Funding provided by Istituto Italiano di Tecnologia within the CRUI-CARE Agreement.Peer reviewe