Meta-analysis of grey matter changes and their behavioral characterization in patients with alcohol use disorder

Abstract

Alcohol Use Disorder (AUD) is associated with reductions in grey matter (GM) volume which can lead to changes in numerous brain functions. The results of previous studies on altered GM in AUD differ considerably in the regions identified. Three meta-analyses carried out between 2014 and 2017 yielded different results. The present study includes the considerable amount of newer research and delivers a state-of-the art meta-analysis in line with recently published guidelines. Additionally, we behaviorally characterized affected regions using fMRI metadata and identified related brain networks by determining their meta-analytic connectivity patterns. Twenty-seven studies with 1,045 AUD patients and 1,054 healthy controls were included in the analysis and analyzed by means of Anatomical Likelihood Estimation (ALE). GM alterations were identified in eight clusters covering different parts of the cingulate and medial frontal gyri, paracentral lobes, left post- and precentral gyri, left anterior and right posterior insulae and left superior frontal gyrus. The behavioral characterization associated these regions with specific cognitive, emotional, somatosensory and motor functions. Moreover, the clusters represent nodes within behaviorally relevant brain networks. Our results suggest that GM reduction in AUD could disrupt network communication responsible for the neurocognitive impairments associated with high chronic alcohol consumption.

Figure 1

Flow diagram on the different phases of the systematic literature search. ¹Differences in numbers of excluded articles and exclusion reasons result from studies excluded because of multiple exclusion criteria.

Figure 2

Foci-distribution of the experiments included in the ALE meta-analysis. Foci are depicted on a grey matter glass brain. Red Blobs: Foci; A: anterior; S: superior; P: posterior; L: left; R: right. This image was created with Mango v4.1. (http://ric.uthscsa.edu/mango/).

Figure 3

Results of the ALE meta-analysis. The highlighted clusters (C1–C8) represent significant convergence about grey matter differences in AUD patients compared to healthy controls. (a) Clusters are depicted on brain slices of an MNI standard brain. Color indicates ALE value. (b) Spatial position and expansion of the ALE-clusters depicted on a grey matter glass brain. Cluster-forming threshold p < 0.001, family wise error (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/).

Figure 4

Behavioral domain profile of the ALE derived cluster-network. Only domains with an effect size of Z > 3 are shown, as this is significant after correction for the size of the ROI/mask and the number of domains.

Figure 5

Paradigm Analysis of the ALE derived cluster-network. Only domains with an effect size of Z > 3.3 are shown, as this is significant after correction for the size of the ROI/mask and the number of domains.

Figure 6

Results from the meta-analytic connectivity modelling (MACM). Left: Seed regions (ALE cluster), right: MACM-maps. All clusters were significant at a cluster-forming threshold of p < 0.001 and FWE cluster level corrected at p < 0.05. Z values indicate axial slice position in Talairach space. This image was created with Mango v4.1. (http://ric.uthscsa.edu/mango/).