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Chemotherapy-induced functional changes of the default mode network in patients with lung cancer

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Abstract

Previous studies have demonstrated that cognitive impairment is associated with neurophysiological changes in lung cancer following chemotherapy. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in patients with lung cancer revealed by resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI scans were acquired from 21 post-chemotherapy and 27 non-chemotherapy lung cancer patients and 30 healthy controls. All groups were age, gender and education-matched. The posterior cingulate cortex (PCC) was chosen as the seed region to detect the FC patterns and then determine whether these changes were related with specific cognitive performance. Compared with non-chemotherapy lung cancer patients, chemotherapy patients revealed decreased FC between the PCC and the right anterior cingulate cortex (ACC), left inferior parietal lobule (IPL), and left medial prefrontal cortex (mPFC), as well as increased FC with the left postcentral gyrus (PoCG). Relative to healthy controls, post-chemotherapy patients exhibited reduced FC between the PCC and the left ACC and left temporal lobe, as well as increased FC with the right PoCG. Moreover, the decreased FC of the PCC to bilateral ACC in post-chemotherapy patients was positively associated with reduced MoCA scores (left: r = 0.529, p = 0.029; right: r = 0.577, p = 0.015). The current study mainly demonstrated reduced resting-state FC pattern within the DMN regions that was linked with impaired cognitive function in lung cancer patients after chemotherapy. These findings illustrated the potential role of the DMN in lung cancer patients that will provide novel insight into the underlying neuropathological mechanisms in chemotherapy-induced cognitive impairment.

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References

  • Agrawal, V., Coroller, T. P., Hou, Y., Lee, S. W., Romano, J. L., Baldini, E. H., Chen, A. B., Jackman, D. M., Kozono, D., Swanson, S. J., Wee, J. O., Aerts, H. J. W. L., & Mak, R. H. (2016). Radiologic-pathologic correlation of response to chemoradiation in resectable locally advanced NSCLC. Lung Cancer, 102, 1–8.

    PubMed  Google Scholar 

  • Ahles, T. A., & Saykin, A. J. (2002). Breast cancer chemotherapy-related cognitive dysfunction. Clinical Breast Cancer, 3(3), S84–S90.

    CAS  PubMed  Google Scholar 

  • Arriagada, R., Le Chevalier, T., Borie, F., Riviere, A., Chomy, P., Monnet, I., et al. (1995). Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Journal of the National Cancer Institute, 87(3), 183–190.

    CAS  PubMed  Google Scholar 

  • Ashburner, J., & Friston, K. J. (2005). Unified segmentation. Neuroimage, 26(3), 839–851. https://doi.org/10.1016/j.neuroimage.2005.02.018.

    Article  PubMed  Google Scholar 

  • Bromis, K., Gkiatis, K., Karanasiou, I., Matsopoulos, G., Karavasilis, E., Papathanasiou, M., et al. (2017). Altered brain functional connectivity in small-cell lung Cancer patients after chemotherapy treatment: A resting-state fMRI study. Computational and Mathematical Methods in Medicine, 1403940(10), 17.

    Google Scholar 

  • Bush, G., Luu, P., & Posner, M. I. (2000). Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Sciences, 4(6), 215–222.

    CAS  PubMed  Google Scholar 

  • Cees De Groot, J., De Leeuw, F.E., Oudkerk, M., Van Gijn, J., Hofman, A., Jolles, J., et al. (2000). Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 47(2), 145–151.

  • Correa, D., Root, J., Kryza-Lacombe, M., Mehta, M., Karimi, S., Hensley, M., et al. (2017). Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: A pilot study. Brain Imaging and Behavior, 11(6), 1652–1663.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Damoiseaux, J. S., Rombouts, S. A., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., et al. (2006). Consistent resting-state networks across healthy subjects. Proceedings of the National Academy of Sciences of the United States of America, 103(37), 13848–13853.

    CAS  PubMed  PubMed Central  Google Scholar 

  • de Groot, J.C., De Leeuw, F.-E., Oudkerk, M., Hofman, A., Jolles, J., and Breteler, M. (2001). Cerebral white matter lesions and subjective cognitive dysfunction The Rotterdam Scan Study. Neurology, 56(11), 1539–1545.

  • Deprez, S., Amant, F., Yigit, R., Porke, K., Verhoeven, J., Van den Stock, J., et al. (2011). Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Human Brain Mapping, 32(3), 480–493.

    PubMed  Google Scholar 

  • Ettinger, D. S., Wood, D. E., Aisner, D. L., Akerley, W., Bauman, J., Chirieac, L. R., D'Amico, T. A., DeCamp, M. M., Dilling, T. J., Dobelbower, M., Doebele, R. C., Govindan, R., Gubens, M. A., Hennon, M., Horn, L., Komaki, R., Lackner, R. P., Lanuti, M., Leal, T. A., Leisch, L. J., Lilenbaum, R., Lin, J., Loo, B. W., Jr., Martins, R., Otterson, G. A., Reckamp, K., Riely, G. J., Schild, S. E., Shapiro, T. A., Stevenson, J., Swanson, S. J., Tauer, K., Yang, S. C., Gregory, K., & Hughes, M. (2017). Non-small cell lung Cancer, version 5.2017, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 15(4), 504–535.

    PubMed  Google Scholar 

  • Fox, M. D., & Raichle, M. E. (2007). Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nature Reviews. Neuroscience, 8(9), 700–711. https://doi.org/10.1038/nrn2201.

    Article  CAS  PubMed  Google Scholar 

  • Fransson, P., & Marrelec, G. (2008). The precuneus/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis. Neuroimage, 42(3), 1178–1184. https://doi.org/10.1016/j.neuroimage.2008.05.059.

    Article  PubMed  Google Scholar 

  • Galea, M., & Woodward, M. (2005). Mini-mental state examination (MMSE). The Australian Journal of Physiotherapy, 51(3), 198.

    PubMed  Google Scholar 

  • Grosshans, D. R., Meyers, C. A., Allen, P. K., Davenport, S. D., & Komaki, R. (2008). Neurocognitive function in patients with small cell lung cancer : Effect of prophylactic cranial irradiation. Cancer, 112(3), 589–595.

    PubMed  Google Scholar 

  • Hong, Q. Y., Wu, G. M., Qian, G. S., Hu, C. P., Zhou, J. Y., Chen, L. A., Li, W. M., Li, S. Y., Wang, K., Wang, Q., Zhang, X. J., Li, J., Gong, X., Bai, C. X., & on behalf of the Lung Cancer Group of the Chinese Thoracic Society; Chinese Alliance Against Lung Cancer. (2015). Prevention and management of lung cancer in China. Cancer, 121(Suppl 17), 3080–3088. https://doi.org/10.1002/cncr.29584.

    Article  PubMed  Google Scholar 

  • Inagaki, M., Yoshikawa, E., Matsuoka, Y., Sugawara, Y., Nakano, T., Akechi, T., Wada, N., Imoto, S., Murakami, K., Uchitomi, Y., & and The Breast Cancer Survivors' Brain MRI Database Group. (2007). Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer, 109(1), 146–156. https://doi.org/10.1002/cncr.22368.

    Article  PubMed  Google Scholar 

  • Johnson, B. E., Grayson, J., Makuch, R. W., Linnoila, R. I., Anderson, M. J., Cohen, M. H., Glatstein, E., Minna, J. D., & Ihde, D. C. (1990). Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Journal of Clinical Oncology, 8(3), 396–401.

    CAS  PubMed  Google Scholar 

  • Kaasa, S., Olsnes, B. T., Thorud, E., & Host, H. (1988). Reduced short-term neuropsychological performance in patients with nonsmall-cell lung cancer treated with cisplatin and etoposide. Antibiotics and Chemotherapy (1971), 41, 226–231.

    CAS  Google Scholar 

  • Kam, J. W., Boyd, L. A., Hsu, C. L., Liu-Ambrose, T., Handy, T. C., Lim, H. J., et al. (2016). Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: An fMRI study. Brain Imaging and Behavior, 10(3), 840–848.

    PubMed  Google Scholar 

  • Kesler, S. R. (2014). Default mode network as a potential biomarker of chemotherapy-related brain injury. Neurobiology of Aging, 35(2), 15.

    Google Scholar 

  • Kesler, S. R., Wefel, J. S., Hosseini, S. H., Cheung, M., Watson, C. L., & Hoeft, F. (2013). Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls. Proceedings of the National Academy of Sciences, 110(28), 11600–11605.

    CAS  Google Scholar 

  • Kesler, S. R., Adams, M., Packer, M., Rao, V., Henneghan, A. M., Blayney, D. W., & Palesh, O. (2017). Disrupted brain network functional dynamics and hyper-correlation of structural and functional connectome topology in patients with breast cancer prior to treatment. Brain and Behavior, 7(3), e00643.

    PubMed  PubMed Central  Google Scholar 

  • Kim, S. S., Gomez-Ramirez, M., Thakur, P. H., & Hsiao, S. S. (2015). Multimodal interactions between proprioceptive and cutaneous signals in primary somatosensory cortex. Neuron, 86(2), 555–566.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, M. H., Smyser, C. D., & Shimony, J. S. (2013). Resting-state fMRI: A review of methods and clinical applications. American Journal of Neuroradiology, 34(10), 1866–1872.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lowe, M. J., Mock, B. J., & Sorenson, J. A. (1998). Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations. Neuroimage, 7(2), 119–132. https://doi.org/10.1006/nimg.1997.0315.

    Article  CAS  PubMed  Google Scholar 

  • Maldjian, J. A., Laurienti, P. J., Kraft, R. A., & Burdette, J. H. (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage, 19(3), 1233–1239.

    PubMed  Google Scholar 

  • Meyers, C. A., Byrne, K. S., & Komaki, R. (1995). Cognitive deficits in patients with small cell lung cancer before and after chemotherapy. Lung Cancer, 12(3), 231–235.

    CAS  PubMed  Google Scholar 

  • Miao, H., Chen, X., Yan, Y., He, X., Hu, S., Kong, J., Wu, M., Wei, Y., Zhou, Y., Wang, L., Wang, K., & Qiu, B. (2016). Functional connectivity change of brain default mode network in breast cancer patients after chemotherapy. Neuroradiology, 58(9), 921–928.

    PubMed  Google Scholar 

  • Molina, J. R., Yang, P., Cassivi, S. D., Schild, S. E., & Adjei, A. A. (2008). Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proceedings, 83(5), 584–594.

  • Nanavaty, P., Alvarez, M. S., & Alberts, W. M. (2014). Lung cancer screening: Advantages, controversies, and applications. Cancer Control, 21(1), 9–14. https://doi.org/10.1177/107327481402100102.

    Article  PubMed  Google Scholar 

  • Nasreddine, Z. S., Phillips, N. A., Bédirian, V., Charbonneau, S., Whitehead, V., Collin, I., et al. (2005). The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53(4), 695–699.

    PubMed  Google Scholar 

  • Pomykala, K. L., de Ruiter, M. B., Deprez, S., McDonald, B. C., & Silverman, D. H. (2013). Integrating imaging findings in evaluating the post-chemotherapy brain. Brain Imaging and Behavior, 7(4), 436–452. https://doi.org/10.1007/s11682-013-9239-y.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., & Shulman, G. L. (2001). A default mode of brain function. Proceedings of the National Academy of Sciences, 98(2), 676–682.

    CAS  Google Scholar 

  • Rosazza, C., & Minati, L. (2011). Resting-state brain networks: Literature review and clinical applications. Neurological Sciences, 32(5), 773–785.

    PubMed  Google Scholar 

  • Simo, M., Root, J. C., Vaquero, L., Ripolles, P., Jove, J., Ahles, T., et al. (2015). Cognitive and brain structural changes in a lung cancer population. Journal of Thoracic Oncology, 10(1), 38–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Simo, M., Vaquero, L., Ripolles, P., Gurtubay-Antolin, A., Jove, J., Navarro, A., et al. (2016). Longitudinal brain changes associated with prophylactic cranial irradiation in lung Cancer. Journal of Thoracic Oncology, 11(4), 475–486.

    PubMed  Google Scholar 

  • Simo, M., Rifa-Ros, X., Vaquero, L., Ripolles, P., Cayuela, N., Jove, J., et al. (2018). Brain functional connectivity in lung cancer population: An exploratory study. Brain Imaging and Behavior, 12(2), 369–382.

    CAS  PubMed  Google Scholar 

  • Tao, L., Lin, H., Yan, Y., Xu, X., Wang, L., Zhang, J., & Yu, Y. (2017). Impairment of the executive function in breast cancer patients receiving chemotherapy treatment: A functional MRI study. European Journal of Cancer Care, 26(6), e12553.

    Google Scholar 

  • Torre, L. A., Bray, F., Siegel, R. L., Ferlay, J., Lortet-Tieulent, J., & Jemal, A. (2015). Global cancer statistics, 2012. CA: a Cancer Journal for Clinicians, 65(2), 87–108.

    Google Scholar 

  • Wahlund, L.-O., Barkhof, F., Fazekas, F., Bronge, L., Augustin, M., Sjögren, M., et al. (2001). A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke, 32(6), 1318–1322.

  • Wang, J., Zuo, X., & He, Y. (2010). Graph-based network analysis of resting-state functional MRI. Frontiers in Systems Neuroscience, 4, 16.

    PubMed  PubMed Central  Google Scholar 

  • Wefel, J. S., Vardy, J., Ahles, T., & Schagen, S. B. (2011). International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. The Lancet Oncology, 12(7), 703–708.

    PubMed  Google Scholar 

  • Welzel, T., Niethammer, A., Mende, U., Heiland, S., Wenz, F., Debus, J., & Krempien, R. (2008). Diffusion tensor imaging screening of radiation-induced changes in the white matter after prophylactic cranial irradiation of patients with small cell lung cancer: First results of a prospective study. AJNR. American Journal of Neuroradiology, 29(2), 379–383.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Whitney, K. A., Lysaker, P. H., Steiner, A. R., Hook, J. N., Estes, D. D., & Hanna, N. H. (2008). Is"chemobrain" a transient state? A prospective pilot study among persons with non-small cell lung cancer. The Journal of Supportive Oncology, 6(7), 313–321.

    PubMed  Google Scholar 

  • Xuan, H., Chen Gan, W. L., Huang, Z., Wang, L., Jia, Q., Chen, Z., et al. (2017). Altered network efficiency of functional brain networks in patients with breast cancer after chemotherapy. Oncotarget, 8(62), 105648.

    PubMed  PubMed Central  Google Scholar 

  • 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.

    PubMed  Google Scholar 

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Funding

This work was supported by a grant from the National Natural Science Foundation of China (No. 81601477), Jiangsu Provincial Special Program of Medical Science (No. BE2017614), Youth Medical Talents of Jiangsu Province (No. QNRC2016062), 14th “Six Talent Peaks” Project of Jiangsu Province (No. YY-079), and Nanjing Outstanding Youth Fund (No. JQX17006).

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  1. Yujie Zhang and Yu-Chen Chen contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China

    Yujie Zhang, Yu-Chen Chen, Lanyue Hu, Jia You, Huiyou Chen, Cunnan Mao & Xindao Yin

  2. Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China

    Wei Gu & Qian Li

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  1. Yujie Zhang
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Zhang, Y., Chen, YC., Hu, L. et al. Chemotherapy-induced functional changes of the default mode network in patients with lung cancer. Brain Imaging and Behavior 14, 847–856 (2020). https://doi.org/10.1007/s11682-018-0030-y

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