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Brain connectivity patterns associated with duration of abstinence in methamphetamine use disorder

Nature Mental Health volume 3, pages 1256–1266 (2025) Cite this article

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Abstract

Methamphetamine use disorder (MUD) is a substantial public health crisis characterized by neurobiological abnormalities. Although neurofunctional variations across abstinence stages are documented, brain connectivity patterns associated with abstinence duration remain poorly characterized. In this cross-sectional study, we characterize brain connectivity patterns associated with abstinence duration in MUD. We hypothesize that whole-brain functional connectivity patterns would covary with abstinence duration in MUD. Applying connectome-based predictive modeling with leave-one-out cross-validation to resting-state functional connectivity data from participants with MUD stratified by abstinence duration (<1 month, 1–3 months, 3–6 months, 6–24 months; total N = 85), we identified patterns significantly associated with abstinence duration (r = 0.51, P < 0.001), validated in an independent cohort (N = 48, r = 0.41, P < 0.004). These patterns comprised positive components showing strengthened within-network connectivity in motor/sensory, subcortical and medial frontal networks, and enhanced between-network connectivity involving motor/sensory, cerebellum/brainstem and subcortical networks, and negative components demonstrating reduced connectivity between motor/sensory and default mode networks, as well as among motor/sensory, medial frontal and visual association networks. Exploratory analyses revealed systematic variation in strength, with healthy comparison individuals exhibiting intermediate connectivity relative to individuals who were short-term (<1 month) versus prolonged (6–24 months) MUD-abstinent. Our findings reveal cross-sectional associations between abstinence duration and brain connectivity in MUD.

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Fig. 1: Flowchart of the cross-sectional study.
The alternative text for this image may have been generated using AI.
Fig. 2: Study design and sample sizes for each analysis.
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Fig. 3: Positive and negative abstinence-duration-associated connectivity patterns.
The alternative text for this image may have been generated using AI.
Fig. 4: Connectivity strength of combined, positive and negative patterns of individuals with MUD and HCs.
The alternative text for this image may have been generated using AI.
Fig. 5: Theoretical model of MUD abstinence-duration-associated connectivity patterns.
The alternative text for this image may have been generated using AI.

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Data availability

Due to ethical considerations and consent limitations, these data cannot be publicly shared. For data access, please contact M.Z. All requests will be evaluated on a case-by-case basis. Access requires submission of a research proposal and approval from an ethics committee. We commit to responding to all requests within 30 days.

Code availability

Data analysis and visualization for this study were performed using Python (version 3.9.20). The CPM was executed using previously validated custom Python scripts, available at https://github.com/esfinn/cpm_tutorial. Masks of the MUD abstinence-duration-associated connectivity patterns can be accessed from the GitHub repository at https://github.com/ZhongGangliang/Methamphetamine-Abstinence-Networks.git. Any further information required to reanalyze the data reported in this article can be obtained from the corresponding author upon request.

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Acknowledgements

We extend our sincere appreciation to all the individuals and organizations who contributed to the completion of this article. This work was funded by the National Key R&D Program of China (2023YFC3304204, J.D.; 2023YFC3304200, J.D.; 2019HY320001, M.Z.), the National Natural Science Foundation (82130041, M.Z.; 82171484, J.D.; 81871045, J.D.; 82201650, T.C.; 82171485, N.Z.), the STI2030-Major Projects (2021ZD0202105, H.J., 2022ZD0211100, N.Z.) and the Medical-Engineering Interdisciplinary Research Foundation of Shanghai Jiao Tong University ‘Jiao Tong Star’ Program (YG2023ZD25, J.D.). None of the funding bodies played any role in the study’s conceptualization, design, data collection, analysis, decision to publish or manuscript preparation.

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Authors and Affiliations

  1. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Gangliang Zhong, Tianzhen Chen, Hang Su, Xiaotong Li, Na Zhong, Haifeng Jiang, Jiang Du & Min Zhao

  2. Department of Psychology and Behavioral Sciences, Zhejiang University, Hangzhou, Zhejiang, China

    Yuzheng Hu

  3. Department of Psychiatry and the Child Study Center, Yale School of Medicine, New Haven, CT, USA

    Marc N. Potenza

  4. The Connecticut Mental Health Center, New Haven, CT, USA

    Marc N. Potenza

  5. The Connecticut Council on Problem Gambling, Wethersfield, CT, USA

    Marc N. Potenza

  6. The Wu Tsai Institute and Department of Neuroscience, Yale University, New Haven, CT, USA

    Marc N. Potenza

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  1. Gangliang Zhong
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Contributions

G.Z. took charge of the study design, data collection and organization and drafted the paper. T.C. contributed to the study design, patient recruitment, data collection and initial data organization. H.S. and X.L. were mainly responsible for patient recruitment and data collection, with H.S. also handling initial data organization. N.Z. and H.J. participated in the study design, patient recruitment and data collection, and assisted with data interpretation. Y.H. provided expert insights into data interpretation. M.N.P., J.D. and M.Z. conceptualized the project. M.N.P. supervised the research, while J.D. and M.Z. additionally secured funding and oversaw all aspects of the study, ensuring its successful execution and ethical compliance.

Corresponding authors

Correspondence to Marc N. Potenza, Jiang Du or Min Zhao.

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Nature Mental Health thanks Martin Fungisai Gerchen, Mark S. Gold and Kaustubh Kulkarni for their contribution to the peer review of this work.

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Zhong, G., Chen, T., Su, H. et al. Brain connectivity patterns associated with duration of abstinence in methamphetamine use disorder. Nat. Mental Health 3, 1256–1266 (2025). https://doi.org/10.1038/s44220-025-00499-z

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