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Nicotine in action: cigarette smoking modulated homotopic functional connectivity in schizophrenia

  • Wei Liao
  • Siqi Yang
  • Jiao Li
  • Yun-Shuang Fan
  • Xujun Duan
  • Qian Cui
  • Huafu Chen
ORIGINAL RESEARCH
  • 30 Downloads

Abstract

Cigarette smoking is intimately associated with both early onset and increased severity of schizophrenia. The self-medication hypothesis suggests that nicotine can relieve or restore neurocognitive deficits and symptoms associated with schizophrenia. Schizophrenia patients and healthy subjects who smoked showed deficits in communication between their hemispheres. These homotopic connectivity mechanisms associated with both schizophrenia and smoking comorbidity were largely unknown until now. A mixed sample including patients with schizophrenia (22 smokers and 27 non-smokers) and healthy controls (22 smokers and 21 non-smokers) based on clinical diagnoses and cigarette dependence were recruited for the current study. All subjects underwent resting-state functional magnetic resonance imaging to determine possible interactions between schizophrenia and smoking, and to determine the main effects of schizophrenia and smoking on homotopic functional connectivity. Decreased homotopic functional connectivity of the subgenual anterior cingulate cortex suggested a main effect of schizophrenia and smoking—an additive effect. Furthermore, we found an antagonistic interaction effect between schizophrenia and smoking located in the ventrolateral prefrontal cortex (VLPFC). In addition, the connectivity strength of the bilateral VLPFC was negatively correlated with the Positive and Negative Syndrome Scale Negative scores and positively correlated with lifetime smoking. These results suggest that smoking has multiple effects on the modulation of interhemispheric connectivity in schizophrenia. Our findings provide valuable information underlying the pathophysiological mechanisms of schizophrenia and offer a potential target for future clinical treatment of schizophrenia and smoking comorbidity.

Keywords

Cigarette smoking Homotopic functional connectivity Schizophrenia Self-medication Ventrolateral prefrontal cortex Subgenual anterior cingulate cortex 

Notes

Funding

This study was funded by the National Natural Science Foundation of China (61533006, 81471653, 81771919 and 61673089), China Postdoctoral Science Foundation (2013 M532229), Sichuan Science and Technology Program (2018TJPT0016), and the “111” project (B12027).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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.

Supplementary material

11682_2018_1_MOESM1_ESM.docx (492 kb)
ESM 1 (DOCX 491 kb)

References

  1. Addicott, M. A., Sweitzer, M. M., Froeliger, B., Rose, J. E., & McClernon, F. J. (2015). Increased functional connectivity in an insula-based network is associated with improved smoking cessation outcomes. Neuropsychopharmacology, 40(11), 2648–2656.  https://doi.org/10.1038/npp.2015.114.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Adler, L. E., Olincy, A., Waldo, M., Harris, J. G., Griffith, J., Stevens, K., Flach, K., Nagamoto, H., Bickford, P., Leonard, S., & Freedman, R. (1998). Schizophrenia, sensory gating, and nicotinic receptors. Schizophrenia Bulletin, 24(2), 189–202.CrossRefGoogle Scholar
  3. Andreasen, N. C., Pressler, M., Nopoulos, P., Miller, D., & Ho, B. C. (2010). Antipsychotic dose equivalents and dose-years: a standardized method for comparing exposure to different drugs. Biological Psychiatry, 67(3), 255–262.  https://doi.org/10.1016/j.biopsych.2009.08.040.CrossRefPubMedGoogle Scholar
  4. Badre, D., & Wagner, A. D. (2007). Left ventrolateral prefrontal cortex and the cognitive control of memory. Neuropsychologia, 45(13), 2883–2901.CrossRefPubMedGoogle Scholar
  5. Baker, J. T., Holmes, A. J., Masters, G. A., Yeo, B. T., Krienen, F., Buckner, R. L., et al. (2014). Disruption of cortical association networks in schizophrenia and psychotic bipolar disorder. JAMA Psychiatry, 71(2), 109–118.  https://doi.org/10.1001/jamapsychiatry.2013.3469.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bersani, G., Quartini, A., Iannitelli, A., Paolemili, M., Ratti, F., Di Biasi, C., et al. (2010). Corpus callosum abnormalities and potential age effect in men with schizophrenia: an MRI comparative study. Psychiatry Research, 183(2), 119–125.  https://doi.org/10.1016/j.pscychresns.2010.04.011.CrossRefPubMedGoogle Scholar
  7. Bullmore, E., & Sporns, O. (2009). Complex brain networks: graph theoretical analysis of structural and functional systems. Nature Reviews. Neuroscience, 10(3), 186–198.  https://doi.org/10.1038/nrn2575.CrossRefPubMedGoogle Scholar
  8. Camchong, J., MacDonald III, A. W., Bell, C., Mueller, B. A., & Lim, K. O. (2009). Altered functional and anatomical connectivity in schizophrenia. Schizophrenia Bulletin, 37(3), 640–650.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chang, X., Xi, Y. B., Cui, L. B., Wang, H. N., Sun, J. B., Zhu, Y. Q., et al. (2015). Distinct inter-hemispheric dysconnectivity in schizophrenia patients with and without auditory verbal hallucinations. Scientific Reports, 5, 11218.Google Scholar
  10. Chen, X., Lu, B., & Yan, C. G. (2017). Reproducibility of R-fMRI metrics on the impact of different strategies for multiple comparison correction and sample sizes. Human Brain Mapping, 39, 300–318.  https://doi.org/10.1002/hbm.23843.CrossRefPubMedGoogle Scholar
  11. de Leon, J., & Diaz, F. J. (2005). A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors. Schizophrenia Research, 76(2–3), 135–157.  https://doi.org/10.1016/j.schres.2005.02.010.CrossRefGoogle Scholar
  12. de Ruiter, M. B., Veltman, D. J., Goudriaan, A. E., Oosterlaan, J., Sjoerds, Z., & van den Brink, W. (2009). Response perseveration and ventral prefrontal sensitivity to reward and punishment in male problem gamblers and smokers. Neuropsychopharmacology, 34(4), 1027–1038.  https://doi.org/10.1038/npp.2008.175.CrossRefPubMedGoogle Scholar
  13. DeMyer, M. K., Gilmor, R. L., Hendrie, H. C., DeMyer, W. E., Augustyn, G. T., & Jackson, R. K. (1988). Magnetic resonance brain images in schizophrenic and normal subjects: influence of diagnosis and education. Schizophrenia Bulletin, 14(1), 21–37.CrossRefPubMedGoogle Scholar
  14. Eklund, A., Nichols, T. E., & Knutsson, H. (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America, 113(28), 7900–7905.  https://doi.org/10.1073/pnas.1602413113.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Fox, M. D., Buckner, R. L., Liu, H., Chakravarty, M. M., Lozano, A. M., & Pascual-Leone, A. (2014). Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases. Proceedings of the National Academy of Sciences of the United States of America, 111(41), E4367–E4375.  https://doi.org/10.1073/pnas.1405003111.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Friston, K. J., Williams, S., Howard, R., Frackowiak, R. S., & Turner, R. (1996). Movement-related effects in fMRI time-series. Magnetic Resonance in Medicine, 35(3), 346–355.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Galvan, A., Poldrack, R. A., Baker, C. M., McGlennen, K. M., & London, E. D. (2011). Neural correlates of response inhibition and cigarette smoking in late adolescence. Neuropsychopharmacology, 36(5), 970–978.  https://doi.org/10.1038/npp.2010.235.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Goldstein, R. Z., & Volkow, N. D. (2011). Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nature Reviews. Neuroscience, 12(11), 652–669.  https://doi.org/10.1038/nrn3119.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Guo, W., Xiao, C., Liu, G., Wooderson, S. C., Zhang, Z., Zhang, J., Yu, L., & Liu, J. (2014). Decreased resting-state interhemispheric coordination in first-episode, drug-naive paranoid schizophrenia. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 48, 14–19.CrossRefGoogle Scholar
  20. Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., & Fagerstrom, K. O. (1991). The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom tolerance questionnaire. British Journal of Addiction, 86(9), 1119–1127.CrossRefGoogle Scholar
  21. Hoptman, M. J., Zuo, X. N., D'Angelo, D., Mauro, C. J., Butler, P. D., Milham, M. P., & Javitt, D. C. (2012). Decreased interhemispheric coordination in schizophrenia: a resting state fMRI study. Schizophrenia Research, 141(1), 1–7.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Horn, N. R., Dolan, M., Elliott, R., Deakin, J. F., & Woodruff, P. W. (2003). Response inhibition and impulsivity: an fMRI study. Neuropsychologia, 41(14), 1959–1966.CrossRefPubMedGoogle Scholar
  23. Jacobsen, L. K., D'Souza, D. C., Mencl, W. E., Pugh, K. R., Skudlarski, P., & Krystal, J. H. (2004). Nicotine effects on brain function and functional connectivity in schizophrenia. Biological Psychiatry, 55(8), 850–858.  https://doi.org/10.1016/j.biopsych.2003.12.023.CrossRefPubMedGoogle Scholar
  24. Jalili, M., Meuli, R., Do, K. Q., Hasler, M., Crow, T. J., & Knyazeva, M. G. (2010). Attenuated asymmetry of functional connectivity in schizophrenia: a high-resolution EEG study. Psychophysiology, 47(4), 706–716.  https://doi.org/10.1111/j.1469-8986.2009.00971.x.CrossRefPubMedGoogle Scholar
  25. Ji, G. J., Zhang, Z., Xu, Q., Zang, Y. F., Liao, W., & Lu, G. (2014). Generalized tonic-clonic seizures: aberrant interhemispheric functional and anatomical connectivity. Radiology, 271(3), 839–847.  https://doi.org/10.1148/radiol.13131638.CrossRefPubMedGoogle Scholar
  26. Ji, G. J., Zhang, Z., Xu, Q., Wang, Z., Wang, J., Jiao, Q., Yang, F., Tan, Q., Chen, G., Zang, Y. F., Liao, W., & Lu, G. (2015). Identifying Corticothalamic network epicenters in patients with idiopathic generalized epilepsy. AJNR. American Journal of Neuroradiology, 36(8), 1494–1500.  https://doi.org/10.3174/ajnr.A4308.CrossRefPubMedGoogle Scholar
  27. Kay, S. R., Fiszbein, A., & Opler, L. A. (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin, 13(2), 261–276.CrossRefGoogle Scholar
  28. Kelly, C., Zuo, X. N., Gotimer, K., Cox, C. L., Lynch, L., Brock, D., Imperati, D., Garavan, H., Rotrosen, J., Castellanos, F. X., & Milham, M. P. (2011). Reduced interhemispheric resting state functional connectivity in cocaine addiction. Biological Psychiatry, 69(7), 684–692.  https://doi.org/10.1016/j.biopsych.2010.11.022.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Khan, M. S., Boileau, I., Kolla, N., & Mizrahi, R. (2018). A systematic review of the role of the nociceptin receptor system in stress, cognition, and reward: relevance to schizophrenia. Translational Psychiatry, 8(1), 38.  https://doi.org/10.1038/s41398-017-0080-8.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Koukouli, F., Rooy, M., Tziotis, D., Sailor, K. A., O'Neill, H. C., Levenga, J., Witte, M., Nilges, M., Changeux, J. P., Hoeffer, C. A., Stitzel, J. A., Gutkin, B. S., DiGregorio, D. A., & Maskos, U. (2017). Nicotine reverses hypofrontality in animal models of addiction and schizophrenia. Nature Medicine, 23(3), 347–354.  https://doi.org/10.1038/nm.4274.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Krystal, J. H., D'Souza, D. C., Gallinat, J., Driesen, N., Abi-Dargham, A., Petrakis, I., et al. (2006). The vulnerability to alcohol and substance abuse in individuals diagnosed with schizophrenia. Neurotoxicity Research, 10(3–4), 235–252.CrossRefPubMedGoogle Scholar
  32. Leonard, S., Mexal, S., & Freedman, R. (2007). Smoking, genetics and schizophrenia: evidence for self medication. Journal of Dual Diagnosis, 3(3–4), 43–59.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Li, H. J., Xu, Y., Zhang, K. R., Hoptman, M. J., & Zuo, X. N. (2015). Homotopic connectivity in drug-naive, first-episode, early-onset schizophrenia. Journal of Child Psychology and Psychiatry, 56(4), 432–443.CrossRefPubMedGoogle Scholar
  34. Liao, W., Yu, Y., Miao, H. H., Feng, Y. X., Ji, G. J., & Feng, J. H. (2017). Inter-hemispheric intrinsic connectivity as a Neuromarker for the diagnosis of boys with Tourette syndrome. Molecular Neurobiology, 54(4), 2781–2789.  https://doi.org/10.1007/s12035-016-9863-9.CrossRefPubMedGoogle Scholar
  35. Lin, F., Wu, G., Zhu, L., & Lei, H. (2013). Heavy smokers show abnormal microstructural integrity in the anterior corpus callosum: a diffusion tensor imaging study with tract-based spatial statistics. Drug and Alcohol Dependence, 129(1), 82–87.CrossRefPubMedGoogle Scholar
  36. Moran, L. V., Sampath, H., Stein, E. A., & Hong, L. E. (2012). Insular and anterior cingulate circuits in smokers with schizophrenia. Schizophrenia Research, 142(1), 223–229.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Moran, L. V., Sampath, H., Kochunov, P., & Hong, L. E. (2013). Brain circuits that link schizophrenia to high risk of cigarette smoking. Schizophrenia Bulletin, 39(6), 1373–1381.  https://doi.org/10.1093/schbul/sbs149.CrossRefGoogle Scholar
  38. Moran, L. V., Betts, J. M., Ongur, D., & Janes, A. C. (2017). Neural responses to smoking cues in schizophrenia. Schizophrenia Bulletin.  https://doi.org/10.1093/schbul/sbx1085.
  39. Patkar, A. A., Gopalakrishnan, R., Lundy, A., Leone, F. T., Certa, K. M., & Weinstein, S. P. (2002). Relationship between tobacco smoking and positive and negative symptoms in schizophrenia. The Journal of Nervous and Mental Disease, 190(9), 604–610.  https://doi.org/10.1097/01.NMD.0000030525.40247.B9.CrossRefPubMedGoogle Scholar
  40. Potvin, S., Lungu, O., Lipp, O., Lalonde, P., Zaharieva, V., Stip, E., Melun, J. P., & Mendrek, A. (2016). Increased ventro-medial prefrontal activations in schizophrenia smokers during cigarette cravings. Schizophrenia Research, 173(1–2), 30–36.  https://doi.org/10.1016/j.schres.2016.03.011.CrossRefGoogle Scholar
  41. Power, J. D., Barnes, K. A., Snyder, A. Z., Schlaggar, B. L., & Petersen, S. E. (2012). Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage, 59(3), 2142–2154.  https://doi.org/10.1016/j.neuroimage.2011.10.018.CrossRefGoogle Scholar
  42. Resnick, S. M. (1992). Matching for education in studies of schizophrenia. Archives of General Psychiatry, 49(3), 246.CrossRefPubMedGoogle Scholar
  43. Ribolsi, M., Koch, G., Magni, V., Di Lorenzo, G., Rubino, I. A., Siracusano, A., et al. (2009). Abnormal brain lateralization and connectivity in schizophrenia. Reviews in the Neurosciences, 20(1), 61–70.CrossRefPubMedGoogle Scholar
  44. Roland, J. L., Snyder, A. Z., Hacker, C. D., Mitra, A., Shimony, J. S., Limbrick, D. D., Raichle, M. E., Smyth, M. D., & Leuthardt, E. C. (2017). On the role of the corpus callosum in interhemispheric functional connectivity in humans. Proceedings of the National Academy of Sciences of the United States of America, 114, 13278–13283.  https://doi.org/10.1073/pnas.1707050114.CrossRefPubMedPubMedCentralGoogle Scholar
  45. Rossi, A., Stratta, P., di Michele, V., de Cataldo, S., & Cassacchia, M. (1991). Lateral ventricular size, educational level and patient subtypes in schizophrenia. The British Journal of Psychiatry, 159, 443–444.CrossRefPubMedGoogle Scholar
  46. Saliba, M., Assaad, S., Haddad, C., Hallit, S., Hachem, D., & Haddad, G. (2017). Schizophrenia and smoking: impact on negative symptoms. Revista inteRnacional de investigación en adicciones, 1, 28–35.CrossRefGoogle Scholar
  47. Savjani, R. R., Velasquez, K. M., Thompson-Lake, D. G. Y., Baldwin, P. R., Eagleman, D. M., De La Garza II, R., et al. (2014). Characterizing white matter changes in cigarette smokers via diffusion tensor imaging. Drug and Alcohol Dependence, 145, 134–142.CrossRefPubMedGoogle Scholar
  48. Schuepbach, D., Keshavan, M. S., Kmiec, J. A., & Sweeney, J. A. (2002). Negative symptom resolution and improvements in specific cognitive deficits after acute treatment in first-episode schizophrenia. Schizophrenia Research, 53(3), 249–261.CrossRefPubMedGoogle Scholar
  49. Schwartz, R. C. (2007). Concurrent validity of the global assessment of functioning scale for clients with schizophrenia. Psychological Reports, 100(2), 571–574.  https://doi.org/10.2466/pr0.100.2.571-574.CrossRefGoogle Scholar
  50. Schwarzkopf, D. S., De Haas, B., & Rees, G. (2012). Better ways to improve standards in brain-behavior correlation analysis. Frontiers in Human Neuroscience, 6, 200.  https://doi.org/10.3389/fnhum.2012.00200.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Smucny, J., Olincy, A., & Tregellas, J. R. (2016). Nicotine restores functional connectivity of the ventral attention network in schizophrenia. Neuropharmacology, 108, 144–151.  https://doi.org/10.1016/j.neuropharm.2016.04.015.CrossRefPubMedPubMedCentralGoogle Scholar
  52. Sturmer, T., Glynn, R. J., Lee, I. M., Christen, W. G., & Hennekens, C. H. (2000). Lifetime cigarette smoking and colorectal cancer incidence in the Physicians' health study I. Journal of the National Cancer Institute, 92(14), 1178–1181.CrossRefPubMedGoogle Scholar
  53. Viswanath, H., Velasquez, K. M., Thompson-Lake, D. G., Savjani, R., Carter, A. Q., Eagleman, D., et al. (2015). Alterations in interhemispheric functional and anatomical connectivity are associated with tobacco smoking in humans. Front Hum Neurosci, 9,  https://doi.org/10.3389/fnhum.2015.00116.
  54. Walterfang, M., Wood, A. G., Reutens, D. C., Wood, S. J., Chen, J., Velakoulis, D., McGorry, P. D., & Pantelis, C. (2008). Morphology of the corpus callosum at different stages of schizophrenia: cross-sectional study in first-episode and chronic illness. The British Journal of Psychiatry, 192(6), 429–434.  https://doi.org/10.1192/bjp.bp.107.041251.CrossRefPubMedGoogle Scholar
  55. Walterfang, M., Wood, A. G., Reutens, D. C., Wood, S. J., Chen, J., Velakoulis, D., McGorry, P. D., & Pantelis, C. (2009). Corpus callosum size and shape in first-episode affective and schizophrenia-spectrum psychosis. Psychiatry Research, 173(1), 77–82.  https://doi.org/10.1016/j.pscychresns.2008.09.007.CrossRefPubMedGoogle Scholar
  56. Winterer, G. (2010). Why do patients with schizophrenia smoke? Current Opinion in Psychiatry, 23(2), 112–119.  https://doi.org/10.1097/YCO.0b013e3283366643.CrossRefPubMedGoogle Scholar
  57. Yan, C. G., Wang, X. D., Zuo, X. N., & Zang, Y. F. (2016). DPABI: Data Processing & Analysis for (resting-state) brain imaging. Neuroinformatics, 14(3), 339–351.  https://doi.org/10.1007/s12021-016-9299-4.CrossRefPubMedPubMedCentralGoogle Scholar
  58. Yang, G. J., Murray, J. D., Repovs, G., Cole, M. W., Savic, A., Glasser, M. F., Pittenger, C., Krystal, J. H., Wang, X. J., Pearlson, G. D., Glahn, D. C., & Anticevic, A. (2014). Altered global brain signal in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 111(20), 7438–7443.  https://doi.org/10.1073/pnas.1405289111.CrossRefPubMedPubMedCentralGoogle Scholar
  59. Yang, G. J., Murray, J. D., Glasser, M., Pearlson, G. D., Krystal, J. H., Schleifer, C., Repovs, G., & Anticevic, A. (2017). Altered global signal topography in schizophrenia. Cerebral Cortex, 27(11), 5156–5169.  https://doi.org/10.1093/cercor/bhw297.CrossRefPubMedGoogle Scholar
  60. Yokoyama, N., Sasaki, H., Mori, Y., Ono, M., Tsurumi, K., Kawada, R., Matsumoto, Y., Yoshihara, Y., Sugihara, G., Miyata, J., Murai, T., & Takahashi, H. (2017). Additive effect of cigarette smoking on gray matter abnormalities in schizophrenia. Schizophrenia Bulletin.  https://doi.org/10.1093/schbul/sbx1092.
  61. Yu, D., Yuan, K., Bi, Y., Luo, L., Zhai, J., Liu, B., et al. (2017). Altered interhemispheric resting-state functional connectivity in young male smokers. Addiction Biology, 23(2), 772–780.Google Scholar
  62. Zhang, X., Stein, E. A., & Hong, L. E. (2010). Smoking and schizophrenia independently and additively reduce white matter integrity between striatum and frontal cortex. Biological Psychiatry, 68(7), 674–677.  https://doi.org/10.1016/j.biopsych.2010.06.018.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Zhang, R., Wei, Q., Kang, Z., Zalesky, A., Li, M., Xu, Y., Li, L., Wang, J., Zheng, L., Wang, B., Zhao, J., Zhang, J., & Huang, R. (2015). Disrupted brain anatomical connectivity in medication-naive patients with first-episode schizophrenia. Brain Structure & Function, 220(2), 1145–1159.  https://doi.org/10.1007/s00429-014-0706-z.CrossRefGoogle Scholar
  64. Zuo, X. N., Kelly, C., Di Martino, A., Mennes, M., Margulies, D. S., Bangaru, S., et al. (2010). Growing together and growing apart: Regional and sex differences in the lifespan developmental trajectories of functional homotopy. The Journal of Neuroscience, 30(45), 15034–15043.  https://doi.org/10.1523/JNEUROSCI.2612-10.2010.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Wei Liao
    • 1
    • 2
  • Siqi Yang
    • 1
    • 2
  • Jiao Li
    • 1
    • 2
  • Yun-Shuang Fan
    • 1
    • 2
  • Xujun Duan
    • 1
    • 2
  • Qian Cui
    • 3
  • Huafu Chen
    • 1
    • 2
  1. 1.The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for NeuroinformationUniversity of Electronic Science and Technology of ChinaChengduPeople’s Republic of China
  2. 2.School of Life Science and Technology, Center for Information in BioMedicineUniversity of Electronic Science and Technology of ChinaChengduPeople’s Republic of China
  3. 3.School of Public AdministrationUniversity of Electronic Science and Technology of ChinaChengduPeople’s Republic of China

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