Multimodal Neuroimaging Study of Structural and Functional Brain Alterations in Individuals with Opioid Use Disorder

Academic Background

Opioid Use Disorder (OUD) is a complex chronic condition that has multifaceted negative impacts on an individual’s life and is closely associated with an increased risk of mortality. In 2021, over 80,000 deaths in the United States were attributed to opioid overdose. Although medications for OUD, such as methadone, can reduce mortality and improve quality of life, many questions remain unanswered regarding the mechanisms of these medications and opioids at the large-scale neural network level.

In recent years, structural and functional neuroimaging studies have begun to uncover the neural mechanisms associated with OUD. Structural MRI studies have shown alterations in brain regions involved in reward, cognition, and emotional processing, such as the striatum, prefrontal cortex, insula, and amygdala. Functional MRI (fMRI) studies suggest that OUD involves systemic changes in the default mode network, salience network, and frontoparietal network. However, previous research has been limited by small sample sizes, few female participants, and single-modality analyses, leading to inconsistent findings.

Therefore, this study aims 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), filling a critical gap in the field.

Source of the Paper

This study was led by Saloni Mehta from Yale School of Medicine, with contributions from scholars at Vanderbilt University, Roger Williams Medical Center, Brigham and Women’s Hospital, and other institutions. The paper was published in December 2024 in the journal Radiology, titled Alterations in Volume and Intrinsic Resting-State Functional Connectivity Detected at Brain MRI in Individuals with Opioid Use Disorder.

Research Process and Results

Research Process

This study is a secondary analysis of the “Collaboration Linking Opioid Use Disorder and Sleep” (CLOUDS) study. It compares structural and functional brain differences between individuals with OUD receiving methadone treatment and healthy controls. The research process includes the following steps:

1. Participant Recruitment: OUD patients were recruited from a single clinic, aged ≥18 years, meeting the DSM-5 criteria for OUD, and stabilized on methadone treatment within the past 24 weeks. Healthy controls were recruited from a separate transdiagnostic study, with no known neurological or mental health diagnoses.

2. Neuroimaging Acquisition: All participants underwent non-contrast brain MRI scans on three 3T MRI scanners, including high-resolution T1-weighted 3D volume imaging and 6-minute resting-state fMRI.

3. Data Analysis:

   • Structural Analysis: Tensor-Based Morphometry (TBM) was used to analyze T1-weighted MRI data, quantifying regional brain volume changes.
   • Functional Analysis: Intrinsic Connectivity Distribution (ICD) was used to analyze rsfMRI data, assessing functional connectivity at each voxel.
   • Statistical Analysis: Voxel-wise linear regression models were employed to assess group differences, with multiple comparison corrections.

Key Results

1. Structural Differences:

   • OUD participants showed significantly smaller volumes in the bilateral thalamus (β = -17.42), right caudate and orbitofrontal cortex (β = -11.32), and right medial temporal lobe (β = -8.02) compared to healthy controls.
   • OUD participants had significantly larger volumes in the brainstem (β = 15.21), midbrain (β = 13.04), cerebellum (right β = 14.96, left β = 14.88), and left insula (β = 10.73) compared to healthy controls.
   • In the OUD group, female participants had significantly larger volumes in the right medial prefrontal cortex than male participants, while the opposite was true in the healthy control group.

2. Functional Differences:

   • OUD participants showed significantly increased functional connectivity in the left thalamus (β = 0.50), right medial temporal lobe (β = 0.43), right cerebellum (β = 0.46), and brainstem (β = 0.48).
   • No evidence of reduced functional connectivity or sex-by-group interactions was observed.

3. Structure-Function Correlations:

   • Positive correlations between structural and functional alterations were found in the cerebellum (r = 0.32) and brainstem (r = 0.23), but not in the thalamus or medial temporal lobe.

Conclusions and Significance

This study found overlapping structural and functional brain alterations in individuals with OUD, particularly in opioid receptor-dense regions such as the thalamus, medial temporal lobe, cerebellum, and brainstem. These results align with previous research and provide new directions for future studies on the neural mechanisms of opioid use and misuse.

Scientific and Practical Value

1. Scientific Value: This study, through multimodal neuroimaging methods, reveals widespread structural and functional brain alterations in individuals with OUD, particularly in opioid receptor-dense regions. This provides important insights into the neural mechanisms of OUD.
2. Practical Value: The findings offer potential biomarkers for the diagnosis and treatment of OUD, with structural and functional alterations in the cerebellum and brainstem potentially serving as future intervention targets.

Research Highlights

1. Key Findings: Individuals with OUD showed significant structural and functional alterations in the thalamus, medial temporal lobe, cerebellum, and brainstem, with these changes being particularly pronounced in female participants.
2. Methodological Innovation: This study employed whole-brain data-driven methods, avoiding the limitations of hypothesis-driven approaches and providing a more comprehensive understanding of the neural mechanisms of OUD.
3. Sample Characteristics: The study included a higher proportion of female participants, enhancing the generalizability of the results.

Additional Valuable Information

The study’s limitations include the potential influence of polysubstance use in the OUD group and the fact that all participants were receiving methadone treatment. Future research should validate these findings in other OUD samples. Additionally, longitudinal studies and animal models will help further elucidate the causal relationships underlying these alterations.

This study provides critical evidence for understanding the neural mechanisms of OUD and lays the groundwork for future diagnostic and therapeutic research.