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.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Salling, M. C., & Martinez, D. (2016). Brain stimulation in addiction. Neuropsychopharmacology, 41(12), 2798–2809. https://doi.org/10.1038/npp.2016.80.
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.
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.
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.19126.96.36.1994.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
We thank Mr. Xinhai Wu for contributions to the recruitment of heroin-dependent subjects.
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).
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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.
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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
- Heroin dependence
- Protracted abstinence
- Methadone maintenance treatment
- Psychophysiological interaction