Functional connectivity of posterior cingulate gyrus in heroin dependents treated by methadone maintenance and protracted abstinence measures: an event-related fMRI study

Abstract

Protracted abstinence (PA) and Methadone maintenance treatment (MMT) are two main types of heroin addiction treatment, however, the effects of both measures on the functional connectivity (FC) of the brain in heroin dependents in the drug cue event-related response are unclear. Functional magnetic resonance imaging (fMRI) based drug cue-reactivity task has been widely used in addiction research, which may provide a new way to understand the change of brain function during a certain period of treatment. The default function network (DMN) with posterior cingulate cortex (PCC) as the core is generally involved in the process of addiction. The aim of the present study was to explore the brain response of FC in patients with heroin-dependent during PA, MMT treatment under task-fMRI. Twenty-two heroin-dependent patients during PA, 18 heroin-dependent patients during MMT and 16 healthy control (HC) individuals were included to conduct the heroin cue-reactivity task during fMRI. The MMT and PA patients’ subjective craving for heroin was evaluated. The psychophysiological interaction (PPI) analysis of SPM12 was used to get FC during the task state. There was a significant difference on FC between PCC and the right medial Prefrontal Cortex (mPFC) in three groups. The post-hoc analysis showed that there was a significant difference of brain regions between the MMT and the PA group. The FC of PCC-mPFC in the MMT group was significantly stronger than that in the PA group. Compared with the PA group, the FC of the DMN in the MMT group was significantly increased under drug cue response. Therefore, PA is more beneficial for the heroin-dependent patients to lower the salience value of drug related cues, in turn to reduce relapse risks. It also reflected the important role of PCC-mPFC pathway in heroin dependents induced by heroin cues.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. Bechara, A. (2005). Decision making, impulse control and loss of willpower to resist drugs: A neurocognitive perspective. Nature Neuroscience, 8(11), 1458–1463. https://doi.org/10.1038/nn1584.

    CAS  Article  PubMed  Google Scholar 

  2. Biswal, B., Yetkin, F. Z., Haughton, V. M., & Hyde, J. S. (1995). Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magnetic Resonance in Medicine, 34(4), 537–541.

    CAS  Article  Google Scholar 

  3. Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The brain's default network: Anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 1–38. https://doi.org/10.1196/annals.1440.011.

    Article  PubMed  Google Scholar 

  4. De Luca, M., Beckmann, C. F., De Stefano, N., Matthews, P. M., & Smith, S. M. (2006). fMRI resting state networks define distinct modes of long-distance interactions in the human brain. Neuroimage, 29(4), 1359–1367. https://doi.org/10.1016/j.neuroimage.2005.08.035.

    Article  PubMed  Google Scholar 

  5. Denier, N., Gerber, H., Vogel, M., Klarhofer, M., Riecher-Rossler, A., Wiesbeck, G. A., et al. (2013). Reduction in cerebral perfusion after heroin administration: A resting state arterial spin labeling study. PLoS One, 8(9), e71461. https://doi.org/10.1371/journal.pone.0071461.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. Di, X., & Biswal, B. B. (2017). Psychophysiological interactions in a visual checkerboard task: Reproducibility, reliability, and the effects of Deconvolution. Frontiers in Neuroscience, 11, 573. https://doi.org/10.3389/fnins.2017.00573.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Fox, M. D., Snyder, A. Z., Vincent, J. L., Corbetta, M., Van Essen, D. C., & Raichle, M. E. (2005). The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proceedings of the National Academy of Sciences of the United States of America, 102(27), 9673–9678. https://doi.org/10.1073/pnas.0504136102.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Fox, M. D., Corbetta, M., Snyder, A. Z., Vincent, J. L., & Raichle, M. E. (2006). Spontaneous neuronal activity distinguishes human dorsal and ventral attention systems. Proceedings of the National Academy of Sciences of the United States of America, 103(26), 10046–10051. https://doi.org/10.1073/pnas.0604187103.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Friston, K. J., Buechel, C., Fink, G. R., Morris, J., Rolls, E., & Dolan, R. J. (1997). Psychophysiological and modulatory interactions in neuroimaging. Neuroimage, 6(3), 218–229. https://doi.org/10.1006/nimg.1997.0291.

    CAS  Article  PubMed  Google Scholar 

  10. Fu, L. P., Bi, G. H., Zou, Z. T., Wang, Y., Ye, E. M., Ma, L., Ming-Fan, & Yang, Z. (2008). Impaired response inhibition function in abstinent heroin dependents: An fMRI study. Neuroscience Letters, 438(3), 322–326. https://doi.org/10.1016/j.neulet.2008.04.033.

    CAS  Article  PubMed  Google Scholar 

  11. Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100(1), 253–258. https://doi.org/10.1073/pnas.0135058100.

    CAS  Article  PubMed  Google Scholar 

  12. Hunter, M. D., Eickhoff, S. B., Miller, T. W., Farrow, T. F., Wilkinson, I. D., & Woodruff, P. W. (2006). Neural activity in speech-sensitive auditory cortex during silence. Proceedings of the National Academy of Sciences of the United States of America, 103(1), 189–194. https://doi.org/10.1073/pnas.0506268103.

    CAS  Article  PubMed  Google Scholar 

  13. Hutchison, R. M., Womelsdorf, T., Allen, E. A., Bandettini, P. A., Calhoun, V. D., Corbetta, M., Della Penna, S., Duyn, J. H., Glover, G. H., Gonzalez-Castillo, J., Handwerker, D. A., Keilholz, S., Kiviniemi, V., Leopold, D. A., de Pasquale, F., Sporns, O., Walter, M., & Chang, C. (2013). Dynamic functional connectivity: Promise, issues, and interpretations. Neuroimage, 80, 360–378. https://doi.org/10.1016/j.neuroimage.2013.05.079.

    Article  PubMed  Google Scholar 

  14. Jones, J. D., Sherwin, E., Martinez, S., & Comer, S. D. (2020). Naloxone-induced withdrawal in individuals with and without fentanyl-positive urine samples. The American Journal on Addictions, 29(1), 51–56. https://doi.org/10.1111/ajad.12979.

    Article  PubMed  Google Scholar 

  15. Kober, H., Mende-Siedlecki, P., Kross, E. F., Weber, J., Mischel, W., Hart, C. L., & Ochsner, K. N. (2010). Prefrontal-striatal pathway underlies cognitive regulation of craving. Proceedings of the National Academy of Sciences of the United States of America, 107(33), 14811–14816. https://doi.org/10.1073/pnas.1007779107.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kreek, M. J. (2000). Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Annals of the New York Academy of Sciences, 909, 186–216.

    CAS  Article  Google Scholar 

  17. Lerman, C., Gu, H., Loughead, J., Ruparel, K., Yang, Y., & Stein, E. A. (2014). Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function. JAMA Psychiatry, 71(5), 523–530. https://doi.org/10.1001/jamapsychiatry.2013.4091.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Li, Q., Wang, Y., Zhang, Y., Li, W., Yang, W., Zhu, J., Wu, N., Chang, H., Zheng, Y., Qin, W., Zhao, L., Yuan, K., Liu, J., Wang, W., & Tian, J. (2012). Craving correlates with mesolimbic responses to heroin-related cues in short-term abstinence from heroin: An event-related fMRI study. Brain Research, 1469, 63–72. https://doi.org/10.1016/j.brainres.2012.06.024.

    CAS  Article  PubMed  Google Scholar 

  19. Li, Q., Wang, Y., Zhang, Y., Li, W., Zhu, J., Zheng, Y., Chen, J., Zhao, L., Zhou, Z., Liu, Y., Wang, W., & Tian, J. (2013). Assessing cue-induced brain response as a function of abstinence duration in heroin-dependent individuals: An event-related fMRI study. PLoS One, 8(5), e62911. https://doi.org/10.1371/journal.pone.0062911.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Li, Q., Li, W., Wang, H., Wang, Y., Zhang, Y., Zhu, J., Zheng, Y., Zhang, D., Wang, L., Li, Y., Yan, X., Chang, H., Fan, M., Li, Z., Tian, J., Gold, M. S., Wang, W., & Liu, Y. (2015). Predicting subsequent relapse by drug-related cue-induced brain activation in heroin addiction: An event-related functional magnetic resonance imaging study. Addiction Biology, 20(5), 968–978. https://doi.org/10.1111/adb.12182.

    CAS  Article  PubMed  Google Scholar 

  21. Li, W., Li, Q., Wang, Y., Zhu, J., Ye, J., Yan, X., Li, Y., Chen, J., Liu, J., Li, Z., Wang, W., & Liu, Y. (2016). Methadone-induced damage to white matter integrity in methadone maintenance patients: A longitudinal self-control DTI study. Scientific Reports, 6, 19662. https://doi.org/10.1038/srep19662.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Liu, H., Hao, Y., Kaneko, Y., Ouyang, X., Zhang, Y., Xu, L., Xue, Z., & Liu, Z. (2009). Frontal and cingulate gray matter volume reduction in heroin dependence: Optimized voxel-based morphometry. Psychiatry and Clinical Neurosciences, 63(4), 563–568. https://doi.org/10.1111/j.1440-1819.2009.01989.x.

    Article  PubMed  Google Scholar 

  23. Ma, N., Liu, Y., Fu, X. M., Li, N., Wang, C. X., Zhang, H., Qian, R. B., Xu, H. S., Hu, X., & Zhang, D. R. (2011). Abnormal brain default-mode network functional connectivity in drug addicts. PLoS One, 6(1), e16560. https://doi.org/10.1371/journal.pone.0016560.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Mazoyer, B., Zago, L., Mellet, E., Bricogne, S., & Etard, O. (2001). Cortical networks for working memory and executive functions sustain the conscious resting state in man. Brain Research Bulletin, 54(3), 287–298.

    CAS  Article  Google Scholar 

  25. McClure, S. M., & Bickel, W. K. (2014). A dual-systems perspective on addiction: Contributions from neuroimaging and cognitive training. Annals of the New York Academy of Sciences, 1327, 62–78. https://doi.org/10.1111/nyas.12561.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Motzkin, J. C., Baskin-Sommers, A., Newman, J. P., Kiehl, K. A., & Koenigs, M. (2014). Neural correlates of substance abuse: Reduced functional connectivity between areas underlying reward and cognitive control. Human Brain Mapping, 35(9), 4282–4292. https://doi.org/10.1002/hbm.22474.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Nir, Y., Hasson, U., Levy, I., Yeshurun, Y., & Malach, R. (2006). Widespread functional connectivity and fMRI fluctuations in human visual cortex in the absence of visual stimulation. Neuroimage, 30(4), 1313–1324. https://doi.org/10.1016/j.neuroimage.2005.11.018.

    Article  PubMed  Google Scholar 

  28. Palamar, J. J., Shearston, J. A., Dawson, E. W., Mateu-Gelabert, P., & Ompad, D. C. (2016). Nonmedical opioid use and heroin use in a nationally representative sample of us high school seniors. Drug and Alcohol Dependence, 158, 132–138. https://doi.org/10.1016/j.drugalcdep.2015.11.005.

    Article  PubMed  Google Scholar 

  29. Pandria, N., Kovatsi, L., Vivas, A. B., & Bamidis, P. D. (2018). Resting-state abnormalities in heroin-dependent individuals. Neuroscience, 378, 113–145. https://doi.org/10.1016/j.neuroscience.2016.11.018.

    CAS  Article  PubMed  Google Scholar 

  30. Pfeifer, J. H., & Allen, N. B. (2012). Arrested development? Reconsidering dual-systems models of brain function in adolescence and disorders. Trends in Cognitive Sciences, 16(6), 322–329. https://doi.org/10.1016/j.tics.2012.04.011.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Raichle, M. E., & Snyder, A. Z. (2007). A default mode of brain function: A brief history of an evolving idea. Neuroimage, 37(4), 1083–1090; discussion 1097-1089. https://doi.org/10.1016/j.neuroimage.2007.02.041.

    Article  PubMed  Google Scholar 

  32. Ries, M. L., McLaren, D. G., Bendlin, B. B., Guofanxu, R., Birn, R. H. A., et al. (2012). Medial prefrontal functional connectivity--relation to memory self-appraisal accuracy in older adults with and without memory disorders. Neuropsychologia, 50(5), 603–611. https://doi.org/10.1016/j.neuropsychologia.2011.12.014.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Rushworth, M. F., Buckley, M. J., Behrens, T. E., Walton, M. E., & Bannerman, D. M. (2007). Functional organization of the medial frontal cortex. Current Opinion in Neurobiology, 17(2), 220–227. https://doi.org/10.1016/j.conb.2007.03.001.

    CAS  Article  PubMed  Google Scholar 

  34. Salling, M. C., & Martinez, D. (2016). Brain stimulation in addiction. Neuropsychopharmacology, 41(12), 2798–2809. https://doi.org/10.1038/npp.2016.80.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Shen, Y., Cao, X., Tan, T., Shan, C., Wang, Y., Pan, J., He, H., & Yuan, T. F. (2016). 10-Hz repetitive Transcranial magnetic stimulation of the left dorsolateral prefrontal cortex reduces heroin Cue craving in long-term addicts. Biological Psychiatry, 80(3), e13–e14. https://doi.org/10.1016/j.biopsych.2016.02.006.

    Article  PubMed  Google Scholar 

  36. Shiffman, S., Balabanis, M. H., Gwaltney, C. J., Paty, J. A., Gnys, M., Kassel, J. D., Hickcox, M., & Paton, S. M. (2007). Prediction of lapse from associations between smoking and situational antecedents assessed by ecological momentary assessment. Drug and Alcohol Dependence, 91(2–3), 159–168. https://doi.org/10.1016/j.drugalcdep.2007.05.017.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Shulman, G. L., Corbetta, M., Buckner, R. L., Fiez, J. A., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common blood flow changes across visual tasks: I. increases in subcortical structures and cerebellum but not in nonvisual cortex. Journal of Cognitive Neuroscience, 9(5), 624–647. https://doi.org/10.1162/jocn.1997.9.5.624.

    CAS  Article  PubMed  Google Scholar 

  38. Smith, D. V., Gseir, M., Speer, M. E., & Delgado, M. R. (2016). Toward a cumulative science of functional integration: A meta-analysis of psychophysiological interactions. Human Brain Mapping, 37(8), 2904–2917. https://doi.org/10.1002/hbm.23216.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sutherland, M. T., McHugh, M. J., Pariyadath, V., & Stein, E. A. (2012). Resting state functional connectivity in addiction: Lessons learned and a road ahead. Neuroimage, 62(4), 2281–2295. https://doi.org/10.1016/j.neuroimage.2012.01.117.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Takaya, S., Liu, H., Greve, D. N., Tanaka, N., Leveroni, C., Cole, A. J., & Stufflebeam, S. M. (2016). Altered anterior-posterior connectivity through the arcuate fasciculus in temporal lobe epilepsy. Human Brain Mapping, 37(12), 4425–4438. https://doi.org/10.1002/hbm.23319.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Volkow, N. D., & Baler, R. D. (2012). Neuroscience. To stop or not to stop? Science, 335(6068), 546–548. https://doi.org/10.1126/science.1218170.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  42. Volkow, N, D. & Blanco, C. (2020). The changing opioid crisis: Development, challenges and opportunities. Molecular Psychiatry, doi:https://doi.org/10.1038/s41380-020-0661-4, 1, 16.

  43. Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., & Telang, F. (2011). Addiction: Beyond dopamine reward circuitry. Proceedings of the National Academy of Sciences of the United States of America, 108(37), 15037–15042. https://doi.org/10.1073/pnas.1010654108.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Volkow, N. D., Frieden, T. R., Hyde, P. S., & Cha, S. S. (2014). Medication-assisted therapies--tackling the opioid-overdose epidemic. The New England Journal of Medicine, 370(22), 2063–2066. https://doi.org/10.1056/NEJMp1402780.

    Article  PubMed  Google Scholar 

  45. Wang, Z., Faith, M., Patterson, F., Tang, K., Kerrin, K., Wileyto, E. P., Detre, J. A., & Lerman, C. (2007). Neural substrates of abstinence-induced cigarette cravings in chronic smokers. The Journal of Neuroscience, 27(51), 14035–14040. https://doi.org/10.1523/JNEUROSCI.2966-07.2007.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. Wang, W., Li, Q., Wang, Y., Tian, J., Yang, W., Li, W., Qin, W., Yuan, K., & Liu, J. (2011). Brain fMRI and craving response to heroin-related cues in patients on methadone maintenance treatment. The American Journal of Drug and Alcohol Abuse, 37(2), 123–130. https://doi.org/10.3109/00952990.2010.543997.

    Article  PubMed  Google Scholar 

  47. Wang, X., Li, B., Zhou, X., Liao, Y., Tang, J., Liu, T., Hu, D., & Hao, W. (2012). Changes in brain gray matter in abstinent heroin addicts. Drug and Alcohol Dependence, 126(3), 304–308. https://doi.org/10.1016/j.drugalcdep.2012.05.030.

    CAS  Article  PubMed  Google Scholar 

  48. Wei, X., Li, W., Chen, J., Li, Y., Zhu, J., Shi, H., Liu, J., Xue, J., Liu, W., Wang, F., Liu, Y., Dang, S., Chen, J., Li, Q., & Wang, W. (2020). Assessing drug cue-induced brain response in heroin dependents treated by methadone maintenance and protracted abstinence measures. Brain Imaging and Behavior, 14(4), 1221–1229. https://doi.org/10.1007/s11682-019-00051-5.

    Article  PubMed  Google Scholar 

  49. Xue, Y. X., Luo, Y. X., Wu, P., Shi, H. S., Xue, L. F., Chen, C., Zhu, W. L., Ding, Z. B., Bao, Y. P., Shi, J., Epstein, D. H., Shaham, Y., & Lu, L. (2012). A memory retrieval-extinction procedure to prevent drug craving and relapse. Science, 336(6078), 241–245. https://doi.org/10.1126/science.1215070.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. Yuan, K., Yu, D., Bi, Y., Wang, R., Li, M., Zhang, Y., Dong, M., Zhai, J., Li, Y., Lu, X., & Tian, J. (2017). The left dorsolateral prefrontal cortex and caudate pathway: New evidence for cue-induced craving of smokers. Human Brain Mapping, 38(9), 4644–4656. https://doi.org/10.1002/hbm.23690.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Zhang, Y., Tian, J., Yuan, K., Liu, P., Zhuo, L., Qin, W., Zhao, L., Liu, J., von Deneen, K. M., Klahr, N. J., Gold, M. S., & Liu, Y. (2011). Distinct resting-state brain activities in heroin-dependent individuals. Brain Research, 1402, 46–53. https://doi.org/10.1016/j.brainres.2011.05.054.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Mr. Xinhai Wu for contributions to the recruitment of heroin-dependent subjects.

Funding

This study was funded by National Natural Science Foundation of China (81771813, 81671661 and 81401393), Technology Innovation Development Foundation of Tangdu Hospital (2013LCYJ003), Reserve Talents Foundation of Tangdu Hospital (2016), Science and Technology Development Fund of the fourth military medical university (2017XD062), China Postdoctoral Science Foundation (2020 M680607), and Research Foundation of Beijing Friendship Hospital, Capital Medical University (yyqdkt2019–31).

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Qiang Li or Wei Li.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interests regarding the publication of this paper.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 815 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wei, X., Chen, J., Zhu, J. et al. Functional connectivity of posterior cingulate gyrus in heroin dependents treated by methadone maintenance and protracted abstinence measures: an event-related fMRI study. Brain Imaging and Behavior (2021). https://doi.org/10.1007/s11682-020-00447-8

Download citation

Keywords

  • Heroin dependence
  • Protracted abstinence
  • Methadone maintenance treatment
  • Craving
  • Psychophysiological interaction