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Mahdi Moghaddam

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YNICL Journal 2026 Journal Article

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

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.