Chemotherapy-induced functional changes of the default mode network in patients with lung cancer
- 10 Downloads
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.
KeywordsLung cancer Functional connectivity Cognitive impairment Default mode network Resting-state fMRI
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).
Compliance with ethical standards
Conflict of interests
The authors declare that there is no potential conflict of interests regarding the publication of this paper.
The current study was approved by the Research Ethics Committee of the Nanjing Medical University.
Informed consent was obtained from all individual participants included in the study.
- 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.CrossRefGoogle 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
- 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.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.Google Scholar
- 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.CrossRefGoogle 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.CrossRefGoogle 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.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle 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.CrossRefGoogle 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., 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.CrossRefGoogle 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.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.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.CrossRefGoogle Scholar