Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder

Laura C Rice; Mackenzie T Langan; Dominic T Cheng; Yi-Shin Sheu; Jutta Peterburs; Jun Hua; Qin Qin; Jessica J Rilee; Monica L Faulkner; Joanna R Mathena; Cynthia A Munro; Gary S Wand; Mary E McCaul; John E Desmond

doi:10.1111/acer.15219

Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder

Alcohol Clin Exp Res (Hoboken). 2024 Jan;48(1):33-47. doi: 10.1111/acer.15219. Epub 2023 Nov 14.

Authors

Laura C Rice¹, Mackenzie T Langan¹, Dominic T Cheng¹, Yi-Shin Sheu¹, Jutta Peterburs^{1

2}, Jun Hua^{3

4}, Qin Qin^{3

4}, Jessica J Rilee¹, Monica L Faulkner¹, Joanna R Mathena¹, Cynthia A Munro¹, Gary S Wand¹, Mary E McCaul¹, John E Desmond¹

Affiliations

¹ Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² Department of Human Medicine, Institute for Systems Medicine, MSH Medical School Hamburg, Hamburg, Germany.
³ Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁴ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA.

PMID: 38206281
PMCID: PMC10784638 (available on 2025-01-01)
DOI: 10.1111/acer.15219

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.

Abstract

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