Resting State Functional Connectivity Patterns Associate with Alcohol Use Disorder Characteristics: Insights from the Triple Network Model

Daniel Guerrero; Mario Dzemidzic; Mahdi Moghaddam; Mintao Liu; Andrea Avena-Koenigsberger; Jaroslaw Harezlak; David A. Kareken; Martin H. Plawecki; Melissa A. Cyders; Joaquín Goñi

arXiv · 2504.06199

Resting State Functional Connectivity Patterns Associate with Alcohol Use Disorder Characteristics: Insights from the Triple Network Model

Daniel Guerrero·Mario Dzemidzic·Mahdi Moghaddam·Mintao Liu·Andrea Avena-Koenigsberger·Jaroslaw Harezlak·David A. Kareken·Martin H. Plawecki·Melissa A. Cyders·Joaquín Goñi

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Abstract

Prolonged alcohol use results in neuroadaptations that mark more severe and treatment-resistant alcohol use. The goal of this study was to identify functional connectivity brain patterns underlying Alcohol Use Disorder (AUD)-related characteristics in fifty-five adults (31 female) who endorsed heavy alcohol use. We hypothesized that resting-state functional connectivity (rsFC) of the Salience (SN), Frontoparietal (FPN), and Default Mode (DMN) networks would reflect self-reported recent and lifetime alcohol use, laboratory-based alcohol seeking, urgency, and sociodemographic characteristics related to AUD. To test our hypothesis, we combined the triple network model (TNM) of psychopathology with a multivariate data-driven approach, regularized partial least squares (rPLS), to unfold concurrent functional connectivity (FC) patterns and their association with AUD-related characteristics. We observed three concurrent associations of interest: i) drinking and age-related cross communication between the SN and both the FPN and DMN; ii) family history density of AUD and urgency anticorrelations between the SN and FPN; and iii) alcohol seeking and sex-associated SN and DMN interactions. These findings provide an integrative interpretation for many individual findings reported in the literature relating functional connectivity signatures and AUD factors. Moreover, we identified a set of neural mechanisms and brain regions concomitant with AUD-related characteristics that can serve as potential treatment targets across clinical and preclinical models.

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Daniel Guerrero, Mario Dzemidzic, Mahdi Moghaddam, Mintao Liu, Andrea Avena-Koenigsberger, Jaroslaw Harezlak, David A. Kareken, Martin H. Plawecki, Melissa A. Cyders, Joaquín Goñi. 2025-04-08. Resting State Functional Connectivity Patterns Associate with Alcohol Use Disorder Characteristics: Insights from the Triple Network Model. https://arxiv.org/abs/2504.06199

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