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Anterior cingulate cortex metabolites and white matter microstructure: a multimodal study of emergent alcohol use disorder

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Abstract

Multimodal imaging is increasingly used to address neuropathology associated with alcohol use disorder (AUD). Few studies have investigated relationships between metabolite concentrations and white matter (WM) integrity; currently, there are no such data in AUD. In this preliminary study, we used complementary neuroimaging techniques, magnetic resonance spectroscopy (MRS), and diffusion weighted imaging (DWI), to study AUD neurophysiology. We tested for relationships between metabolites in the dorsal anterior cingulate cortex (dACC) and adjacent WM microstructure in young adult AUD and control (CON) subjects. Sixteen AUD and fourteen CON underwent whole-brain DWI and MRS of the dACC. Outcomes were dACC metabolites, and diffusion tensor metrics of dACC-adjacent WM. Multiple linear regression terms included WM region, group, and region × group for prediction of dACC metabolites. dACC myo-inositol was positively correlated with axial diffusivity in the left anterior corona radiata (p < 0.0001) in CON but not AUD (group effect: p < 0.001; region × group: p < 0.001; Bonferroni-corrected). In the bilateral anterior corona radiata and right genu of the corpus callosum, glutamate was negatively related to mean diffusivity in AUD, but not CON subjects (all model terms: p < 0.05, uncorrected). In AUD subjects, dACC glutamate was negatively correlated with AUD symptom severity. This is likely the first integrative study of cortical metabolites and WM integrity in young individuals with AUD. Differential relationships between dACC metabolites and adjacent WM tract integrity in AUD could represent early consequences of hazardous drinking, and/or novel biomarkers of early-stage AUD. Additional studies are required to replicate these findings, and to determine the behavioral relevance of these results.

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Funding

This work was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA R01 AA13650, PF; NIAAA F31 AA025518, EJC) and the National Institutes of Health, National Center for Advancing Translational Sciences (UL1TR002529; Indiana Clinical and Translational Sciences Institute; PDT and CTR pilots to HC).

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Authors and Affiliations

  1. Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 355 West 16th Street, GH 4100, Indianapolis, IN, 46202, USA

    Gregory G. Grecco, Evgeny J. Chumin, Mario Dzemidzic, Ulrike Dydak & Karmen K. Yoder

  2. Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA

    Gregory G. Grecco, Evgeny J. Chumin & Karmen K. Yoder

  3. Medical Scientist Training Program, Indiana University School of Medicine, Indianapolis, IN, USA

    Gregory G. Grecco

  4. Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA

    Evgeny J. Chumin, Hu Cheng, Peter Finn & Sharlene Newman

  5. Indiana University Network Science Institute, Bloomington, IN, USA

    Evgeny J. Chumin

  6. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA

    Mario Dzemidzic

  7. School of Health Sciences, Purdue University, West Lafayette, IN, USA

    Ulrike Dydak

  8. Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA

    Karmen K. Yoder

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  1. Gregory G. Grecco
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  4. Hu Cheng
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  8. Karmen K. Yoder
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Contributions

Author contributions included conception (KKY), data collection, acquisition, and processing (GGG, EJC, MD, HC, SN, UD), statistical analysis (GGG, KKY), interpretation of results (GGG, EJC, MD, KKY), drafting the manuscript work or revising it critically for important intellectual content (GGG, EJC, MD, KKY), and approval of final version to be published and agreement to be accountable for the integrity and accuracy of all aspects of the work (all authors).

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Correspondence to Karmen K. Yoder.

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The Institutional Review Board of Indiana University approved this study. All participants provided written informed consent.

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Grecco, G.G., Chumin, E.J., Dzemidzic, M. et al. Anterior cingulate cortex metabolites and white matter microstructure: a multimodal study of emergent alcohol use disorder. Brain Imaging and Behavior 15, 2436–2444 (2021). https://doi.org/10.1007/s11682-020-00443-y

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