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. 2021 May 30;11(6):506.
doi: 10.3390/life11060506.

Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study

Yo-Han Joo  1 , Jeong-Hee Kim  1   2 , Hang-Keun Kim  1   2   3 , Young-Don Son  1   2   3 , Paul Cumming  4   5 , Jong-Hoon Kim  1   3   6
Affiliations

Functional Analysis of Brain Imaging Suggests Changes in the Availability of mGluR5 and Altered Connectivity in the Cerebral Cortex of Long-Term Abstaining Males with Alcohol Dependence: A Preliminary Study

Yo-Han Joo et al. Life (Basel). .

Abstract

Direct in vivo evidence of altered metabotropic glutamate receptor-5 (mGluR5) availability in alcohol-related disorders is lacking. We performed [11C]ABP688 positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI) in prolonged abstinent subjects with alcohol dependence to examine alterations of mGluR5 availability, and to investigate their functional significance relating to neural systems-level changes. Twelve prolonged abstinent male subjects with alcohol dependence (median abstinence duration: six months) and ten healthy male controls underwent [11C]ABP688 PET imaging and 3-Tesla MRI. For mGluR5 availability, binding potential (BPND) was calculated using the simplified reference tissue model with cerebellar gray matter as the reference region. The initial region-of-interest (ROI)-based analysis yielded no significant group differences in mGluR5 availability. The voxel-based analysis revealed significantly lower [11C]ABP688 BPND in the middle temporal and inferior parietal cortices, and higher BPND in the superior temporal cortex in the alcohol dependence group compared with controls. Functional connectivity analysis of the rs-fMRI data employed seed regions identified from the quantitative [11C]ABP688 PET analysis, which revealed significantly altered functional connectivity from the inferior parietal cortex seed to the occipital pole and dorsal visual cortex in the alcohol dependence group compared with the control group. To our knowledge, this is the first report on the combined analysis of mGluR5 PET imaging and rs-fMRI in subjects with alcohol dependence. These preliminary results suggest the possibility of region-specific alterations of mGluR5 availability in vivo and related functional connectivity perturbations in prolonged abstinent subjects.

Keywords: [11C]ABP688; alcohol dependence; functional magnetic resonance imaging; metabotropic glutamate receptor-5; positron emission tomography.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Representative examples of [11C]ABP688 BPND and 3-Tesla MR images of a control subject. (MNI coordinates: x = 3.0 mm, y = -19.5 mm, and z = 4.5 mm).
Figure 2
Figure 2
Results of the voxel-based between-group analysis (a) and correlation analysis between clinical variables and regional mGluR5 availability (b,c). The [11C]ABP688 BPND of the alcohol dependence group was significantly lower in the left middle temporal and inferior parietal cortices and significantly higher in the left superior temporal cortex (uncorrected p < 0.001) (a). The voxel-based analysis with age and the number of cigarettes smoked per day as covariates showed that [11C]ABP688 BPND had significant positive correlations with the duration of alcohol abstinence as shown in (b) (uncorrected p < 0.001) and negative correlations with the duration of illness as shown in (c) (uncorrected p < 0.001). BPND, binding potential with respect to nondisplaceable compartment; Cal, calcarine fissure and surrounding cortex; FG, fusiform gyrus; HP, hippocampus; IFC, inferior frontal cortex; MTC, middle temporal cortex; Oper, opercular part; Orb, orbital part; STC, superior temporal cortex; STP, superior temporal pole; PreC, precentral cortex; PostC, postcentral cortex.
Figure 3
Figure 3
[11C]ABP688 BPND seed-based resting-state functional connectivity. The LIPC to the LOP showed positive connectivity (positive correlation) in the alcohol dependence group, while it showed negative connectivity (anticorrelation) in the control group (p = 0.0002, FDRp = 0.027). The LIPC to the LDVN showed significant positive connectivity (positive correlation) in the alcohol dependence group compared to the control group (p = 0.0003, FDRp = 0.027); LIPC, left inferior parietal cortex; LOP, left occipital pole; LDVN, left visual network region (dorsal part), FDRp, false discovery rate—corrected p-value.
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