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. 2021 Oct;15(5):2436-2444.
doi: 10.1007/s11682-020-00443-y. Epub 2021 Jun 7.

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

Gregory G Grecco  1   2   3 , Evgeny J Chumin  1   2   4   5 , Mario Dzemidzic  1   6 , Hu Cheng  4 , Peter Finn  4 , Sharlene Newman  4 , Ulrike Dydak  1   7 , Karmen K Yoder  8   9   10
Affiliations

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

Gregory G Grecco et al. Brain Imaging Behav. 2021 Oct.

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.

Keywords: Alcohol use disorder; Anterior cingulate cortex; Diffusion weighted imaging; Magnetic resonance spectroscopy; White matter.

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Conflict of interest statement

Conflicts of Interest

The authors report no conflicts of interest.

Figures

Figure 1.
Figure 1.
Dorsal anterior cingulate cortex voxel placement for magnetic resonance spectroscopy.
Figure 2.
Figure 2.
White matter regions of interest used to extract diffusion weighted imaging scalar metrics (Left) Red: anterior corona radiata. Blue: internal capsule. Green: external capsule. Cyan: genu of the corpus callosum. Data were extracted separately for left (L) and right (R) hemispheres. Axial level is z = 5 mm in Montreal Neurological Institute coordinate system.
Figure 3.
Figure 3.
Axial diffusivity in the left anterior corona radiata is positively correlated with dorsal anterior cingulate cortex myo-inositol in controls (CON), but not in emergent alcohol use disorder (AUD) subjects. See text for details regarding the statistical analysis. Myo-inositol concentrations were normalized to creatine. Controls: open circles, dotted trendline. Alcohol use disorder: filled triangles, solid trendline.
Figure 4.
Figure 4.
Mean diffusivity in the left anterior corona radiata is negatively correlated with dorsal anterior cingulate cortex glutamate in emergent alcohol use disorder (AUD), but not control (CON) subjects. Data were similar for the right anterior corona radiata (not shown). See text for details regarding the statistical analysis. Glutamate concentrations were normalized to creatine. Controls: open circles, dotted trendline. Alcohol use disorder: filled triangles, solid trendline.
Figure 5.
Figure 5.
Mean diffusivity in the right genu of the corpus callosum (Genu) radiata is negatively correlated with dorsal anterior cingulate cortex glutamate in emergent alcohol use disorder (AUD) subjects, but not controls (CON). See text for details regarding the statistical analysis. Glutamate concentrations were normalized to creatine. Controls: open circles, dotted trendline. Alcohol use disorder: filled triangles, solid trendline.
See this image and copyright information in PMC

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