Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder

Abstract

Background: Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD-relevant functional networks. The goal of this study is to compare resting-state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL). We hypothesized that group differences in cerebro-cerebellar FC would be present, particularly within the frontoparietal/executive control network (FPN).

Methods: Twenty-eight participants completed a resting-state functional magnetic resonance imaging (rsfMRI) study. CTL participants had no history of AUD, comorbid psychological conditions, or recent heavy drinking and/or drug use. AUD participants had a history of AUD, with sobriety for at least 30 days prior to data collection. Multivariate pattern analysis, an agnostic, whole-brain approach, was used to identify regions with significant differences in FC between groups. Seed-based analyses were then conducted to determine the directionality and extent of these FC differences. Associations between FC strength and executive function were assessed using correlations with Wisconsin Card Sorting Test (WCST) performance.

Results: There were significant group differences in FC in nodes of the FPN, ventral attention network, and default mode network. Post hoc analyses predominantly identified FC differences within the cerebro-cerebellar FPN, with AUD showing significantly less FC within the FPN. In AUD, FC strength between FPN clusters identified in the multivariate pattern analysis (MVPA) analysis (Left Crus II, Right Frontal Cortex) was positively associated with performance on the WCST.

Conclusions: Our results show less engagement of the FPN in individuals with AUD than in CTL. FC strength within this network was positively associated with performance on the WCST. These findings suggest that long-term heavy drinking alters cerebro-cerebellar FC, particularly within networks that are involved in executive function.

Keywords: alcohol abuse; default mode; fMRI; frontoparietal; resting state.

Figure 1.. MVPA Group Contrast Clusters (Control vs. Alcohol).

Regions with significantly different whole-brain FC patterns in the alcohol vs. control groups. Peak level p<.001, cluster level p<.05 (FDR-corrected). PCC = Posterior Cingulate Cortex; MTG = Middle Temporal Gyrus.

Figure 2.. MVPA Direct Group Contrast (Control vs. Alcohol Two Sample t-test) Post-Hoc Seed-to-Voxel Results.

Results for the left posterior cingulate cortex seed are depicted in panel 1); the results for the left middle temporal gyrus seed are shown in panel 2), and the L Crus II/VIIb seed results are shown in panel 3). Regions with significantly different whole-brain FC patterns with respect to the seed in the CTL vs. ALC groups (corresponding to Table 3) are shown in each panel. Peak level p<.001, cluster level p<.05 (FDR-corrected). Positive values (red) indicate CTL > ALC, negative values (blue) indicate ALC > CTL. PCC = Posterior Cingulate Cortex; MTG = Middle Temporal Gyrus.

Figure 3.. MVPA One Sample Contrasts (Control, Alcohol) Post-Hoc Seed-to-Voxel Results.

Regions with significant differences in whole-brain FC patterns from the L Crus II seed (Table 2, Cluster 3), shown separately for the CTL vs. ALC groups (corresponding to Appendices Tables 1 & 2). Results are shown in slices on the left and glass brains (3D-rendered activations on a transparent MNI template) on the right. Peak level p<.001, cluster level p<.05 (FDR-corrected). Positive values (red) indicate positive FC, negative values (blue) indicate negative FC. PC = Posterior Cingulate Cortex; MTG = Middle Temporal Gyrus.

Figure 4.. MVPA Cluster 3 in the context of functional networks.

Left Crus II / Lobule VIIb (red), MVPA analysis result cluster 3, is displayed in the context of the 7 cortical network parcellations. VN = Visual Network, SMN = Somatomotor Network, DAN = Dorsal Attention Network, VAN = Ventral Attention Network, LN = Limbic Network, FPN = Frontoparietal Network, DMN = Default Mode Network.