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Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study

  • SI: Neuroimaging Studies of Cancer and Cancer Treatment
  • Published:
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Abstract

Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, 1 month after, and 1 year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity 1 month after chemotherapy that partially returned to baseline at 1 year in the dorsal attention network. Decreased connectivity was seen in the default mode network at 1 month and 1 year following chemotherapy. In addition, increased subjective memory complaints were noted at 1 month and 1 year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment.

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References

  • Ahles, T. A., Saykin, A. J., McDonald, B. C., Li, Y., Furstenberg, C. T., Hanscom, B. S., Mulrooney, T. J., Schwartz, G. N., & Kaufman, P. A. (2010). Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. Journal of Clinical Oncology, 28, 4434–4440.

    Article  PubMed  Google Scholar 

  • Andrews-Hanna, J. R., Snyder, A. Z., Vincent, J. L., Lustig, C., Head, D., Raichle, M. E., & Buckner, R. L. (2007). Disruption of large-scale brain systems in advanced aging. Neuron, 56, 924–935.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beck, A. T., Steer, R. A., Ball, R., & Ranieri, W. (1996). Comparison of Beck Depression Inventories - IA and -II in psychiatric outpatients. Journal of Personality Assessment, 67(3), 588–597.

    Google Scholar 

  • Biswal, B. B., Mennes, M., Zuo, X. N., Gohel, S., Kelly, C., Smith, S. M., Beckmann, C. F., Adelstein, J. S., Buckner, R. L., Colcombe, S., Dogonowski, A. M., Ernst, M., Fair, D., Hampson, M., Hoptman, M. J., Hyde, J. S., Kiviniemi, V. J., Kotter, R., Li, S. J., Lin, C. P., Lowe, M. J., Mackay, C., Madden, D. J., Madsen, K. H., Margulies, D. S., Mayberg, H. S., McMahon, K., Monk, C. S., Mostofsky, S. H., Nagel, B. J., Pekar, J. J., Peltier, S. J., Petersen, S. E., Riedl, V., Rombouts, S. A., Rypma, B., Schlaggar, B. L., Schmidt, S., Seidler, R. D., Siegle, G. J., Sorg, C., Teng, G. J., Veijola, J., Villringer, A., Walter, M., Wang, L., Weng, X. C., Whitfield-Gabrieli, S., Williamson, P., Windischberger, C., Zang, Y. F., Zhang, H. Y., Castellanos, F. X., & Milham, M. P. (2010). Toward discovery science of human brain function. Proceedings of the National Academy of Sciences of the United States of America, 107, 4734–4739.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bruno, J., Hosseini, S. M., & Kesler, S. (2012). Altered resting state functional brain network topology in chemotherapy-treated breast cancer survivors. Neurobiology of Disease, 48, 329–338.

    Article  PubMed Central  PubMed  Google Scholar 

  • 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 Science, 1124, 1–38.

    Article  Google Scholar 

  • Cohen, J. D., Perlstein, W. M., Braver, T. S., Nystrom, L. E., Noll, D. C., Jonides, J., & Smith, E. E. (1997) Temporal dynamics of brain activation during a working memory task. Nature, 6625, 604–608.

  • Collins, B., Mackenzie, J., Stewart, A., Bielajew, C., & Verma, S. (2009). Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. Psycho-Oncology, 18, 134–143.

    Article  PubMed  Google Scholar 

  • Corbetta, M., & Shulman, G. L. (2002). Control of goal-directed and stimulus driven attention in the brain. Nature Reviews Neuroscience, 3, 201–215.

    Article  CAS  PubMed  Google Scholar 

  • Cox, R. W. (1996). AFNI: software for analysis and visualization of functional magnetic resonance images. Computers and Biomedical Research, 29, 162–173.

    Article  CAS  PubMed  Google Scholar 

  • Damoiseaux, J. S., Beckmann, C. F., Arigita, E. J., Barkhof, F., Scheltens, P., Stam, C. J., Smith, S. M., & Rombouts, S. A. (2008). Reduced resting-state brain activity in the “default network” in normal aging. Cerebral Cortex, 18, 1856–1864.

    Article  CAS  PubMed  Google Scholar 

  • de Ruiter, M. B., Reneman, L., Boogerd, W., Veltman, D. J., van Dam, F. S., Nederveen, A. J., Boven, E., & Schagen, S. B. (2011). Cerebral hyporesponsiveness and cognitive impairment 10 years after chemotherapy for breast cancer. Human Brain Mapping, 32, 1206–1219.

    Article  PubMed  Google Scholar 

  • de Ruiter, M. B., Reneman, L., Boogerd, W., Veltman, D. J., Caan, M., Douaud, G., Lavini, C., Linn, S. C., Boven, E., van Dam, F. S., & Schagen, S. B. (2012). Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Human Brain Mapping, 33, 2971–2983.

    Article  PubMed  Google Scholar 

  • Deprez, S., Amant, F., Smeets, A., Peeters, R., Leemans, A., Van Hecke, W., Verhoeven, J. S., Christiaens, M. R., Vandenberghe, J., Vandenbulcke, M., & Sunaert, S. (2012). Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. Journal of Clinical Oncology, 30, 274–281.

    Article  PubMed  Google Scholar 

  • Fair, D. A., Schlaggar, B. L., Cohen, A. L., Miezin, F. M., Dosenbach, N. U., Wenger, K. K., Fox, M. D., Snyder, A. Z., Raichle, M. E., & Petersen, S. E. (2007). A method for using blocked and event-related fMRI data to study “resting state” functional connectivity. NeuroImage, 35, 396–405.

    Article  PubMed Central  PubMed  Google Scholar 

  • Fan, J., McCandliss, B. D., Sommer, T., Raz, A., & Posner, M. I. (2002). Testing the efficiency and independence of attentional networks. Journal of Cognitive Neuroscience, 14, 340–347.

    Article  PubMed  Google Scholar 

  • First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (2001). Structured clinical interview for DSM-IV-TR axis I disorders-patient edition. Washington, DC: American Psychiatric Press Inc.

    Google Scholar 

  • Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189–198.

    Article  CAS  PubMed  Google Scholar 

  • 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, 9673–9678.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Galvin, J. E., Price, J. L., Yan, Z., Morris, J. C., & Sheline, Y. I. (2011). Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease. Neurology, 76, 1797–1803.

    Article  CAS  PubMed  Google Scholar 

  • Gilewski, M. J., Zelinski, E. M., & Schaie, K. W. (1988). The memory functioning questionnaire for assessment of memory complaints in adulthood and old age. Psychology and Aging, 24, 665–670.

    CAS  Google Scholar 

  • Hacker, C. D., Perlmutter, J., Criswell, S. R., Ances, B. M., & Snyder, A. Z. (2012). Resting state functional connetivity of the striatum in Parkinson’s disease. Brain, 135(Pt 12), 3699–3711.

    Article  PubMed  Google Scholar 

  • Hosseini, S. M., Koovakkattu, D., & Kesler, S. R. (2012). Altered small-world properties of gray matter networks in breast cancer. BMC Neurology, 12, 28.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hutchinson, A. D., Hosking, J. R., Kichenadasse, G., Mattiske, J. K., & Wilson, C. (2012). Objective and subjective cognitive impairment following chemotherapy for cancer: a systematic review. Cancer Treatment Reviews, 38, 926–934.

    Article  PubMed  Google Scholar 

  • Inagaki, M., Yoshikawa, E., Matsuoka, Y., Sugawara, Y., Nakano, T., Akechi, T., Wada, N., Imoto, S., Murakami, K., & Uchitomi, Y. (2007). Smaller regional volumes of brain gray and white matter demonstrated in breast cancer survivors exposed to adjuvant chemotherapy. Cancer, 109, 146–156.

    Article  PubMed  Google Scholar 

  • Jurica, P. J., Leitten, C. L., & Mattis, S. (2001). Dementia rating scale-2 Lutz. FL: Psychological Assessment Resources Inc.

    Google Scholar 

  • Kayl, A. E., Wefel, J. S., & Meyers, C. A. (2006). Chemotherapy and cognition: effects, potential mechanisms, and management. American Journal of Therapeutics, 13, 362–369.

    Article  PubMed  Google Scholar 

  • Kelly, A. M., Uddin, L. Q., Biswal, B. B., Castellanos, F. X., & Milham, M. P. (2008). Competition between functional brain networks mediates behavioral variability. NeuroImage, 39, 527–537.

    Article  PubMed  Google Scholar 

  • Koppelmans, V., Breteler, M. M., Boogerd, W., Seynaeve, C., Gundy, C., & Schagen, S. B. (2012). Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. Journal of Clinical Oncology, 30, 1080–1086.

    Article  PubMed  Google Scholar 

  • Kubler, A., Murphy, K., Kaufman, J., Stein, E. A., & Garavan, H. (2003). Co-ordination within and between verbal and visuospatial working memory: network modulation and anterior frontal recruitment. NeuroImage, 20, 1298–1308.

    Article  CAS  PubMed  Google Scholar 

  • Langner, R., Eickhoff, S. B. (2012). Sustaning attention to simple tasks: A meta-analytic review of the neurao mechanisms of vigilant attention. Psychological Bulletin epub ahead of print.

  • McDonald, B. C., Conroy, S. K., Ahles, T. A., West, J. D., & Saykin, A. J. (2012a). Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study. Journal of Clinical Oncology, 30, 2500–2508.

    Article  PubMed  Google Scholar 

  • McDonald, B. C., Conroy, S. K., Smith, D. J., West, J. D., Saykin, A. J. (2012b). Frontal gray matter reduction after breast cancer chemotherapy and association with executive symptoms: A replication and extension study. Brain Behav Immun.

  • Mills, K. L., Bathula, D., Dias, T. G., Iver, S. P., Fenesy, M. C., Musser, E. D., Stevens, C. A., Thurlow, B. L., Carpenter, S. D., Nagel, B. J., Nigg, J. T., & Fair, D. A. (2012). Altered cortico-striatal-thalamic connectivity in relation to spatial working memory capacity in children with ADHD. Frontiers in Psychiatry, 3, 1–17.

    Article  Google Scholar 

  • Reisberg, B., & Ferris, S. H. (1988). Brief cognitive rating scale (BCRS). Psychopharmacology Bulletin, 24, 629–635.

    CAS  PubMed  Google Scholar 

  • Reuter-Lorenz, P. A., & Cimprich, B. (2013). Cognitive function and breast cancer: promise and potential insights from functional brain imaging. Breast Cancer Research and Treatment, 137, 33–43.

    Article  CAS  PubMed  Google Scholar 

  • Saad, Z. S., Gotts, S. J., Murphy, K., Chen, G., Jo, H. J., Martin, A., & Cox, R. W. (2012). Trouble at rest: how correlation patterns and group differences become distorted after global signal regression. Brain Connectivity, 2, 25–32.

    Article  PubMed  Google Scholar 

  • Schagen, S. B., Muller, M. J., Boogerd, W., Mellenbergh, G. J., & van Dam, F. S. (2006). Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients. Journal of the National Cancer Institute, 98, 1742–1745.

    Article  CAS  PubMed  Google Scholar 

  • Shilling, V., Jenkins, V., Morris, R., Deutsch, G., & Bloomfield, D. (2005). The effects of adjuvant chemotherapy on cognition in women with breast cancer—preliminary results of an observational longitudinal study. The Breast, 14, 142–150.

    Article  CAS  PubMed  Google Scholar 

  • Spreng, R. N., Sepulcre, J., Turner, G. R., Stevens, W. D., & Schacter, D. L. (2012). Intrinsic architecture underlying the relations among the default, dorsal attention, and frontoparietal control networks of the human brain. Journal of Cognitive Neuroscience, 25, 74–86.

    Article  PubMed  Google Scholar 

  • Spreng, R. N., Sepulcre, J., Turner, G. R., Stevens, W. D., & Schacter, D. L. (2013). Intrinsic architecture underlying the relations among the default, dorsal attention, and frontoparietal control networks of the human brain. Journal of Cognitive Neuroscience, 25, 74–86.

    Article  PubMed  Google Scholar 

  • Tomasi, D., & Volkow, N. D. (2012). Aging and functional brain networks. Molecular Psychiatry, 17(471), 549–558.

    Article  PubMed Central  Google Scholar 

  • Vardy, J., & Dhillon, H. (2010). The fog hasn’t lifted on “chemobrain” yet: ongoing uncertainty regarding the effects of chemotherapy and breast cancer on cognition. Breast Cancer Research and Treatment, 123, 35–37.

    Article  PubMed  Google Scholar 

  • Wechsler, D. (1999) Wechsler Abbreviated Scale of Intelligence: The Psychological Corporation.

  • Weis, J., Poppelreuter, M., & Bartsch, H. H. (2009). Cognitive deficits as long-term side-effects of adjuvant therapy in breast cancer patients: ‘subjective’ complaints and ‘objective’ neuropsychological test results. Psycho-Oncology, 18, 775–782.

    Article  CAS  PubMed  Google Scholar 

  • Whitfield-Gabrieli, S., & Ford, J. M. (2012). Default mode network activity and connectivity in psychopathology. Annual Review of Clinical Psychology, 8, 49–76.

    Article  PubMed  Google Scholar 

  • Ystad, M., Hodneland, E., Adolfsdottir, S., Haasz, J., Lundervold, A. J., Eichele, T., & Lundervold, A. (2011). Cortico-striatal connectivity and cognition in normal aging: a combined DTI and resting state fMRI study. NeuroImage, 55, 24–31.

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the Breast Cancer Research Foundation, NIA K01 AG 030380, R01 AG021476, NCRR-00109, DoE SC 0001753. The authors wish to thank the research staff of the University of Vermont CRC and Vermont Cancer Center for their hard work and support of this study. The authors acknowledge the Vermont Advanced Computing Core supported by NASA (NNX 06AC88G) at the University of Vermont for providing High Performance Computing resources that have contributed to the results reported within this paper. The authors also thank Jay Gonyea, Scott Hipko, and Trevor Andrews, Ph.D. from the University of Vermont MRI Center for Biomedical Imaging. We specially thank our volunteers for their dedication to clinical research.

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Authors and Affiliations

  1. Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont College of Medicine, 1 South Prospect St, Burlington, VT, 05401, USA

    Julie A. Dumas, Jenna Makarewicz, Geoffrey J. Schaubhut, Robert Devins, Kimberly Albert & Paul A. Newhouse

  2. Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA

    Kimberly Albert & Paul A. Newhouse

  3. Division of Hematology and Oncology, Vermont Cancer Center, Department of Medicine, University of Vermont College of Medicine, Burlington, VT, USA

    Kim Dittus

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  1. Julie A. Dumas
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Correspondence to Julie A. Dumas.

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Dumas, J.A., Makarewicz, J., Schaubhut, G.J. et al. Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study. Brain Imaging and Behavior 7, 524–532 (2013). https://doi.org/10.1007/s11682-013-9244-1

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