Alterations in Volume and Intrinsic Resting-State Functional Connectivity Detected at Brain MRI in Individuals with Opioid Use Disorder

Abstract

Background Structural and functional MRI studies have revealed brain alterations associated with opioid use disorder (OUD). However, previous research has been limited by small sample sizes, few female participants, and single-modality analyses. Purpose To identify structural and functional brain alterations in individuals with OUD using whole-brain data-driven methods to analyze T1-weighted MRI and resting-state functional MRI (rsfMRI). Materials and Methods This secondary analysis of the Collaboration Linking Opioid Use Disorder and Sleep study compared participants with OUD (data collection February 2021 to February 2023) receiving methadone treatment with healthy control participants (data collection February 2018 to May 2023). T1-weighted MRI and rsfMRI were analyzed using tensor-based morphometry and intrinsic connectivity distribution, respectively. Primary outcome measures included regional brain volumes and functional connectivity. Voxel-wise linear regression was used to assess group differences, with family-wise error correction. Pearson partial correlations were used to examine structure-function relationships. Results Compared with healthy control participants (n = 105; median age, 27 years [IQR, 23-37 years]; 58 female), participants with OUD (n = 103; median age, 37 years [IQR, 31.5-46 years]; 62 male) showed smaller volumes (corrected P < .05) in the thalamus (β = -17.42 [95% CI: -26.56, -8.27]) and right medial temporal lobe (β = -8.02 [95% CI: -12.25, -3.78]). Larger volumes (corrected P < .05) were seen in the brainstem (pons and medulla, β = 15.21 [95% CI: 7.03, 23.40]; midbrain, β = 13.04 [95% CI: 6.61, 19.47]) and cerebellum (right, β = 14.96 [95% CI: 7.25, 22.67]; left, β = 14.88 [95% CI: 7.32, 22.43]). An interaction between sex and group was found for medial prefrontal cortex volume (β = -19.38, corrected P < .05), with female participants having smaller volumes than male participants in the OUD group. Increased functional connectivity (corrected P < .05) was noted in the thalamus (β = 0.50 [95% CI: 0.25, 0.75]), right medial temporal lobe (β = 0.43 [95% CI: 0.21, 0.66]), right cerebellum (β = 0.46 [95% CI: 0.21, 0.71]), and brainstem (β = 0.48 [95% CI: 0.22, 0.74]) in the OUD group. Structure and function were positively correlated in the cerebellum (Pearson r = 0.32 [95% CI: 0.17, 0.44], P < .001) and brainstem (Pearson r = 0.23 [95% CI: 0.09, 0.37], P = .002). Conclusion Individuals with OUD showed overlapping structural and functional brain alterations in opioid receptor-dense regions compared with healthy control participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Filippi and Messina in this issue.

Graphical abstract

Figure 1:

Flowchart of study inclusion and exclusion. Participants with opioid use disorder (OUD) were recruited for the Collaboration Linking Opioid Use Disorder and Sleep (CLOUDS) study, and data from healthy control participants were collected as part of a separate transdiagnostic study. rsfMRI = resting-state functional MRI.

Figure 2:

Tensor-based morphometry (TBM) analysis of T1-weighted MRI scans shows a comparison of brain volumes in participants with opioid use disorder (OUD) and healthy control participants. Widespread volume differences are observed between participants with OUD and healthy controls when accounting for total brain volume. Specifically, the bilateral thalamus, right caudate and orbitofrontal cortex, and right medial temporal lobe show lower volume in participants with OUD compared with healthy controls. The left medial temporal lobe, brainstem, bilateral cerebellum, left insula, and right dorsal posterior cingulate cortex show greater volume in those with OUD compared with healthy controls. All results are shown at P < .05, corrected for multiple comparisons. The color scale indicates the z statistic, whereby blue to pink represents smaller volumes in the OUD group compared with healthy controls, and red to yellow represents larger volumes in the OUD group compared with healthy controls. L = left, R = right.

Figure 3:

(A) Tensor-based morphometry analysis of a T1-weighted MRI scan shows an interaction between sex and group for brain volume in the right medial prefrontal cortex when accounting for total brain volume (P < .05, corrected for multiple comparisons). (B) Post hoc box plot shows the average determinant of Jacobian values from the medial prefrontal cortex cluster for each group stratified according to sex. In the healthy control group, male participants had greater volume in the medial prefrontal cortex. In the opioid use disorder (OUD) group, this pattern was reversed. The solid line in the middle of each box represents the median, and the box represents the IQR.

Figure 4:

Intrinsic connectivity distribution analysis of resting-state functional MRI scans shows a comparison of global resting-state functional connectivity between participants with opioid use disorder (OUD) and healthy control participants. Color scale gradations of yellow indicate greater global connectivity in the bilateral secondary visual areas, left thalamus, right medial temporal lobe, right cerebellum, and brainstem in participants with OUD compared with healthy controls. No clusters of reduced connectivity were observed. All results are shown at P < .05, corrected for multiple comparisons. L = left, R = right.