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Neurophysiological correlate of incubation of craving in individuals with methamphetamine use disorder

Molecular Psychiatry volume 26, pages 6198–6208 (2021)Cite this article

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Abstract

Previous studies both in laboratory animals and humans have reported that abstinence induces incubation of cue-induced drug craving for nicotine, alcohol, cocaine, and methamphetamine. However, current experimental procedures utilized to study incubation of methamphetamine craving do not incorporate the temporal dynamics of neuropsychological measures and electrophysiological activities associated with this incubation process. This study utilized the high-density electroencephalogram (EEG) signals as a rapid, inexpensive, and noninvasive measure of cue-induced craving potential. A total of 156 male individuals with methamphetamine use disorder (MUD) enrolled in this multisite, cross-sectional study. Structured clinical interview data, self-report questionnaires (cued craving, quality of sleep, impulsivity, anxiety, and depression) and resting-state, eye-closed 128 high-density channel EEG signals were collected at 5 abstinence duration time points (<1, 1–3, 3–6, 6–12, and 12–24 months) to track the neuropsychological and neurophysiological signatures. Cue-induced craving was higher after 1–3 months than after the other time points. This incubation effect was also observed for sleep quality but not for anxiety, depression, and impulsivity symptoms, along with exhibited decreased power spectrum for theta (5.5–8 Hz) and alpha (8–13 Hz), and increased in beta (16.5–26.5 Hz) frequency band. Source reconstructed resting-state EEG analysis showed increased synchronization of medial prefrontal cortex (MPFC) for the beta frequency band in 1–3 months abstinent MUD group, and associated with the incubation of craving. Remarkably, the robust incubation-related abnormalities may be driven by beta-band source space connectivity between MPFC and bilateral orbital gyrus (ORB). Our findings suggest the enhancement of beta activity in the incubation period most likely originates from a dysfunction involving frontal brain regions. This neurophysiological signature of incubation of craving can be used to identify individuals who might be most susceptible to relapse, providing a potential insight into future therapeutic interventions for MUD via neuromodulation of beta activity.

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Fig. 1: Schematic overview of the main procedure and analyses of multi-site cross-sectional study.
Fig. 2: Dynamics in neuropsychological measures.
Fig. 3: Fitting curve of cued-craving.
Fig. 4: Analyses on sensor level.
Fig. 5: Source reconstruction of resting-state EEG.
Fig. 6: Abstinent networks summarized by function connectivity between 31 ROIs in 6 networks for four carrier frequencies (theta: 4–8 Hz, alpha: 8–13 Hz, beta: 13–30 Hz, gamma: 30–50 Hz).

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Data and materials availability

Original data are available upon request from corresponding author.

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Acknowledgements

General: We thank Yavin Shaham for critical comments on a draft of the paper. We thank Qian Zhuang, Bin Zhan, Xi He, Yexi Leng, Yaowen Liang, Yan Zeng, and Na Li for helps during data collection.

Funding

NSFC grant (81822017, 32020103008, 31900765), the Science and Technology Commission of Shanghai Municipality (18JC1420302, 18JC1420304), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), Shanghai Sailing Program (19YF1441900), Shanghai Municipal Education Commission - Gaofeng Clinical Medicine Grant Support (20181715). We also thank the support from the Innovative Research Team of High-level Local Universities in Shanghai.

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Authors and Affiliations

  1. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Di Zhao, Weiwen Tian & Ti-Fei Yuan

  2. Research Center of Brain and Cognitive Neuroscience, Liaoning Normal University, Dalian, Liaoning, China

    Mingming Zhang & Wenbo Luo

  3. Da Lian Shan Institute of Addiction Rehabilitation, Nanjing, Jiangsu, China

    Xinyu Cao

  4. Tian Tang He Institute of Addiction Rehabilitation, Beijing, China

    Lu Yin

  5. Tai Hu Institute of Addiction Rehabilitation, Suzhou, Jiangsu, China

    Yi Liu

  6. Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Tian-Le Xu

  7. China Center for Brain Science of Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Tian-Le Xu

  8. Key Laboratory of Brain and Cognitive Neuroscience, Dalian, Liaoning Province, China

    Wenbo Luo

  9. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China

    Ti-Fei Yuan

  10. TianQiao and Chrissy Chen Institute for Translational Research, Shanghai, China

    Ti-Fei Yuan

  11. Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China

    Ti-Fei Yuan

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  1. Di Zhao
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Contributions

TY, WL and DZ conceived and designed the study. DZ, MZ, WT, XC, LY and YL collected the data. DZ, MZ, WT, TX, WL and TY analyzed the data and wrote the paper together.

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Correspondence to Wenbo Luo or Ti-Fei Yuan.

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Zhao, D., Zhang, M., Tian, W. et al. Neurophysiological correlate of incubation of craving in individuals with methamphetamine use disorder. Mol Psychiatry 26, 6198–6208 (2021). https://doi.org/10.1038/s41380-021-01252-5

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