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

Abstract

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.

Altered Global Signal Topography in Alcohol Use Disorders

“…In line with previous findings, AUD patients exhibited impairments in the insula and precuneus regions (Fukushima et al, 2020 ; Bordier et al, 2021 ). Recent fMRI studies have demonstrated that AUD can enhance activation in the insula, inferior frontal gyrus, and precuneus (Noori et al, 2016 ; Quaglieri et al, 2020 ).…”

“…Furthermore, our study indicated that in AUD patients, functional alterations in the precuneus might affect the episodic memory-related circuits. A study has shown that insula as part of the salience network mediates external stimuli-induced attention and arousal responses (Bordier et al, 2021 ). The insula, as the central hub of the salience network, regulates attention shifting between the exogenous and endogenous states.…”

From ensembles to meta-ensembles: Specific reward encoding by correlated network activity

“…These studies will benefit from adopting a network perspective by applying systems level approaches and largely unbiased analyses strategies, as recently demonstrated in a large translational AUD research project ( Sommer et al, 2022 ) and the brain-wide investigation of cFos expression in 123 regions from chronically alcohol-drinking mice using light sheet microscopy that elegantly demonstrated decreased modularity of brain networks ( Kimbrough et al, 2020 ). These results are in line with our findings ( Wandres et al, 2021 ) and supported by recent fMRI results from animals ( Degiorgis et al, 2022 ; Pérez-Ramírez et al, 2022 ) and humans ( Bordier et al, 2022 ; Camchong et al, 2022 ), Targeting network modules, rather than individual brain regions non-invasively, holds therapeutic potential as demonstrated by a clinical trial in AUD patients using transcranial magnetic stimulation of the mPFC ( Harel et al, 2022 ).…”

Aberrant functional brain network organization is associated with relapse during 1‐year follow‐up in alcohol‐dependent patients

“…Similar alterations in global network organization have been shown for patients with AD independent of relapse status, 17–19 although results were not consistent across studies 20 . The present study extends previous work by highlighting deviations in network topology particularly in future relapsers.…”