A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder

Abstract

Introduction: Besides the commonly described gray matter (GM) deficits, there is growing evidence of significant white matter (WM) alterations in patients with alcohol use disorder (AUD). WM changes can be assessed using volumetric and diffusive magnetic resonance imaging methods, such as voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). The aim of the present meta-analysis is to investigate the spatial convergence of the reported findings on WM alterations in AUD.

Methods: Systematic literature search on PubMed and further databases revealed 18 studies eligible for inclusion, entailing a total of 462 AUD patients and 416 healthy controls (up to January 18, 2021). All studies that had used either VBM or DTI whole-brain analyzing methods and reported results as peak-coordinates in standard reference space were considered for inclusion. We excluded studies using approaches non-concordant with recent guidelines for neuroimaging meta-analyses and studies investigating patient groups with Korsakoff syndrome or other comorbid substance use disorders (except tobacco).

Results: Anatomical likelihood estimation (ALE) revealed four significant clusters of convergent macro- and microstructural WM alterations in AUD patients that were assigned to the genu and body of the corpus callosum, anterior and posterior cingulum, fornix, and the right posterior limb of the internal capsule.

Discussion: The changes in WM could to some extent explain the deteriorations in motor, cognitive, affective, and perceptual functions seen in AUD. Future studies are needed to clarify how WM alterations vary over the course of the disorder and to what extent they are reversible with prolonged abstinence.

Fig. 1

Stages of systematic literature search and selection: Flow diagram according to the PRISMA Guideline from Page et al. (2021) [34].

Fig. 2. Results of the ALE meta-analysis.

The highlighted clusters (C1–C4) represent significant convergence of white matter alterations in AUD patients compared to healthy controls. a Clusters are depicted on brain slices of an MNI standard brain. The color indicates the ALE value. b Spatial location and expansion of the ALE clusters depicted on a white matter glass brain. Cluster-forming threshold p < 0.001, FWE cluster level corrected at p < 0.05. x, y, and z values refer to coordinates in MNI space, for detailed MNI peak voxel coordinates of the ALE clusters see Table 2. This image was created with Mango (v4.1., http://ric.uthscsa.edu/mango/) and MRIcroGL (v1.2.20210317, https://www.mccauslandcenter.sc.edu/mricrogl/).