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Functional MRI studies in non-CNS cancers

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

With increasing survival, cognitive problems after systemic treatment for non-CNS cancers are a growing concern. Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging technique that has the potential to uncover the neural circuitry underlying cognitive problems after systemic treatment in cancer patients. Here, we provide an in depth review of the 14 fMRI studies that have been published to date on potential neurotoxic side effects of systemic treatment for non-CNS cancers. Cross-sectional studies in breast cancer survivors show a consistent pattern of hypoactivation in prefrontal and parietal brain regions during various executive functioning tasks 5 to 10 years after completion of adjuvant chemotherapy that are sometimes associated with worse cognitive performance compared to cancer-specific or no-cancer controls. These findings suggest reduced neural functioning as a result of chemotherapy in brain regions that support cognitive functioning. With regard to episodic memory, hypoactivation at encoding is followed by hyperactivation at retrieval, suggestive of impairments in memory encoding that are compensated by neural hyperactivation to perform adequate memory retrieval. Prospective studies of executive functioning and episodic memory show a more complex picture of hypo- and hyperactivation that is possibly due to various counteracting mechanisms relatively shortly after chemotherapy. Two small studies in prostate cancer patients, finally, provide preliminary evidence for reduced activation in task-relevant brain regions after androgen deprivation therapy, suggestive of reduction of neural function. Statistical correction for multiple comparisons in the reviewed studies is typically quite lenient. We suggest that future studies should preferably include larger sample sizes to allow proper statistical correction for multiple comparisons and include comprehensive neurocognitive tests and multimodal MRI to facilitate the interpretation of the observed fMRI findings.

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References

  • Abraham, J., Haut, M. W., Moran, M. T., Filburn, S., Lemieux, S., & Kuwabara, H. (2008). Adjuvant chemotherapy for breast cancer: effects on cerebral white matter seen in diffusion tensor imaging. Clinical Breast Cancer, 8, 88–91.

    Article  PubMed  Google Scholar 

  • Ahles, T. A., Saykin, A. J., McDonald, B. C., Li, Y., Furstenberg, C. T., Hanscom, B. S., et al. (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 

  • Ahles, T. A., Root, J. C., & Ryan, E. L. (2012). Cancer- and cancer treatment-associated cognitive change: an update on the state of the science. Journal of Clinical Oncology, 30, 3675–3686.

    Article  CAS  PubMed  Google Scholar 

  • Barona, A., Reynolds, C. R., & Chastain, R. (1984). A demographically based index of premorbid intelligence for the Wais-R. Journal of Consulting and Clinical Psychology, 52, 885–887.

    Article  Google Scholar 

  • Beck, A. T., & Steer, R. A. (1990). BAI, Beck anxiety inventory. San Antonio: Psychological Corporation.

    Google Scholar 

  • Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Beck depression inventory II. San Antonio: Psychological Coorporation.

    Google Scholar 

  • Benedict, R. H., Schretlen, D., Groninger, L., & Brandt, J. (1998). Hopkins verbal learning test-revised: normative data and analysis of inter-form and test-retest reliability. The Clinical Neuropsychologist, 12, 43–55.

    Article  Google Scholar 

  • Bennett, C. M., & Miller, M. B. (2010). How reliable are the results from functional magnetic resonance imaging? Annals of the New York Academy of Sciences, 1191, 133–155.

    Article  PubMed  Google Scholar 

  • Bracken, B. A., & Howell, K. (2004). Clinical assessment of depression: Professional manual. Odessa: Psychological Assessment Resources.

    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 

  • Bullmore, E., & Sporns, O. (2009). Complex brain networks: graph theoretical analysis of structural and functional systems. Nature Reviews Neuroscience, 10, 186–198.

    Article  CAS  PubMed  Google Scholar 

  • Carp, J. (2012a). On the plurality of (methodological) worlds: estimating the analytic flexibility of FMRI experiments. Frontiers in Neuroscience, 6, 149.

    Article  PubMed Central  PubMed  Google Scholar 

  • Carp, J. (2012b). The secret lives of experiments: methods reporting in the fMRI literature. Neuroimage, 63, 289–300.

    Article  PubMed  Google Scholar 

  • Cella, D. F., Tulsky, D. S., Gray, G., Sarafian, B., Linn, E., Bonomi, A., et al. (1993). The functional assessment of cancer therapy scale: development and validation of the general measure. Journal of Clinical Oncology, 11, 570–557.

    CAS  PubMed  Google Scholar 

  • Chao, H. H., Uchio, E., Zhang, S., Hu, S., Bednarski, S. R., Luo, X., et al. (2012). Effects of androgen deprivation on brain function in prostate cancer patients - a prospective observational cohort analysis. BMC Cancer, 12, 371.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cherrier, M. M., Aubin, S., & Higano, C. S. (2009). Cognitive and mood changes in men undergoing intermittent combined androgen blockade for non-metastatic prostate cancer. Psychooncology, 18, 237–247.

    Article  CAS  PubMed  Google Scholar 

  • Cherrier, M. M., Borghesani, P. R., Shelton, A. L., & Higano, C. S. (2010). Changes in neuronal activation patterns in response to androgen deprivation therapy: a pilot study. BMC Cancer, 10, 1.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cimprich, B., Reuter-Lorenz, P., Nelson, J., Clark, P. M., Therrien, B., Normolle, D., et al. (2010). Prechemotherapy alterations in brain function in women with breast cancer. Journal of Clinical and Experimental Neuropsychology, 32, 324–331.

    Article  PubMed  Google Scholar 

  • Collins, B., Mackenzie, J., Tasca, G. A., Scherling, C., & Smith, A. (2013). Cognitive effects of chemotherapy in breast cancer patients: a dose–response study. Psychooncology, 22, 1517–1527.

    Article  PubMed  Google Scholar 

  • Conroy, S. K., McDonald, B. C., Smith, D. J., Moser, L. R., West, J. D., Kamendulis, L. M., et al. (2013). Alterations in brain structure and function in breast cancer survivors: effect of post-chemotherapy interval and relation to oxidative DNA damage. Breast Cancer Research and Treatment, 137, 493–502.

    Article  CAS  PubMed  Google Scholar 

  • de Ruiter, M. B., Reneman, L., Boogerd, W., Veltman, D. J., van Dam, F. S., Nederveen, A. J., et al. (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., Oosterlaan, J., Veltman, D. J., van den Brink, W., & Goudriaan, A. E. (2012a). Similar hyporesponsiveness of the dorsomedial prefrontal cortex in problem gamblers and heavy smokers during an inhibitory control task. Drug and Alcohol Dependence, 121, 81–89.

    Article  PubMed  Google Scholar 

  • de Ruiter, M. B., Reneman, L., Boogerd, W., Veltman, D. J., Caan, M., Douaud, G., et al. (2012b). 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 

  • Delis, D. C., Kaplan, E., & Kramer, J. H. (2001). Delis-Kaplan Executive Function System (D-KEFS). San Antonio: The Psychological Corporation.

    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, 480–493.

    Article  PubMed  Google Scholar 

  • Deprez, S., Amant, F., Smeets, A., Peeters, R., Leemans, A., Van Hecke, W., et al. (2012). Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. Journal of Clinical Oncology, 30(3), 274–281.

    Article  PubMed  Google Scholar 

  • Eyler, L. T., Sherzai, A., Kaup, A. R., & Jeste, D. V. (2011). A review of functional brain imaging correlates of successful cognitive aging. Biological Psychiatry, 70, 115–122.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ferguson, R. J., McDonald, B. C., Saykin, A. J., & Ahles, T. A. (2007). Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. Journal of Clinical Oncology, 25, 3866–3870.

    Article  PubMed Central  PubMed  Google Scholar 

  • Heaton, R. K., & Staff, P. A. R. (2004). Wisconsin Card Sorting Test Computer Version 4 Research Edition (WCST: CV4). Odessa: Psychological Assessment Resources, Inc.

    Google Scholar 

  • Hesbacher, P. T., Rickels, K., Morris, R. J., Newman, H., & Rosenfeld, H. (1980). Psychiatric illness in family practice. Journal of Clinical Psychiatry, 41, 6–10.

    CAS  PubMed  Google Scholar 

  • Kesler, S. R., Bennett, F. C., Mahaffey, M. L., & Spiegel, D. (2009). Regional brain activation during verbal declarative memory in metastatic breast cancer. Clinical Cancer Research, 15, 6665–6673.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kesler, S. R., Kent, J. S., & O'Hara, R. (2011). Prefrontal cortex and executive function impairments in primary breast cancer. Archives of Neurology, 68, 1447–1453.

    Article  PubMed Central  PubMed  Google Scholar 

  • Koppelmans, V., Groot, M. D., de Ruiter, M. B., Boogerd, W., Seynaeve, C., Vernooij, M. W., et al. (2012). Global and focal white matter integrity in breast cancer survivors 20 years after adjuvant chemotherapy. Human Brain Mapping epub ahead of print.

  • Kriegeskorte, N., Simmons, W. K., Bellgowan, P. S., & Baker, C. I. (2009). Circular analysis in systems neuroscience: the dangers of double dipping. Nature Neuroscience, 12, 535–540.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lopez Zunini, R. A., Scherling, C., Wallis, N., Collins, B., Mackenzie, J., Bielajew, C. et al. (2012). Differences in verbal memory retrieval in breast cancer chemotherapy patients compared to healthy controls: a prospective fMRI study. Brain Imaging and Behavior epub ahead of print.

  • Lorr, M., McNAir, D. M., Heuchert, J. W. P., & Droppleman, L. F. (2003). Profile of Mood States (POMS). Toronto: Multi-Health Systems.

    Google Scholar 

  • McDonald, B. C., Conroy, S. K., Ahles, T. A., West, J. D., & Saykin, A. J. (2012). 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 

  • Nelson, C. J., Lee, J. S., Gamboa, M. C., & Roth, A. J. (2008). Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer, 113, 1097–1106.

    Article  CAS  PubMed  Google Scholar 

  • Petrides, M. (2005). Lateral prefrontal cortex: architectonic and functional organization. Philosophical Transactions of the Royal Society B: Biological Sciences., 360, 781–795.

    Article  Google Scholar 

  • Poldrack, R. A. (2007). Region of interest analysis for fMRI. Social, Cognitive and Affective Neuroscience, 2, 67–70.

    Article  Google Scholar 

  • Poldrack, R. A., Fletcher, P. C., Henson, R. N., Worsley, K. J., Brett, M., & Nichols, T. E. (2008). Guidelines for reporting an fMRI study. Neuroimage, 40, 409–414.

    Article  PubMed Central  PubMed  Google Scholar 

  • Radloff, L. S. (1977). The CES-D scale. A self-report depression scale for research in the general population. Applied Psychological Measurement, 1, 385–401.

    Article  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 

  • Roth, R. M., Isquith, P. K., & Gioia, G. A. (2005). Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A). Lutz: Psychological Assessment Resources.

    Google Scholar 

  • Schagen, S. B., van Dam, F. S., Muller, M. J., Boogerd, W., Lindeboom, J., & Bruning, P. F. (1999). Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. Cancer, 85, 640–650.

    Article  CAS  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 

  • Scherling, C., Collins, B., Mackenzie, J., Bielajew, C., & Smith, A. (2011). Pre-chemotherapy differences in visuospatial working memory in breast cancer patients compared to controls: an FMRI study. Frontiers in Human Neuroscience, 5, 122.

    Article  PubMed Central  PubMed  Google Scholar 

  • Scherling, C., Collins, B., Mackenzie, J., Bielajew, C., & Smith, A. (2012). Prechemotherapy differences in response inhibition in breast cancer patients compared to controls: a functional magnetic resonance imaging study. Journal of Clinical and Experimental Neuropsychology, 34, 543–560.

    Article  PubMed  Google Scholar 

  • Schmand, B., Lindeboom, J., & van Harskamp, F. (1992). De Nederlandse Leestest voor Volwassenen. Lisse: Swets & Zeitlinger.

    Google Scholar 

  • Schöning, S., Engelien, A., Kugel, H., Schafer, S., Schiffbauer, H., Zwitserlood, P., et al. (2007). Functional anatomy of visuo-spatial working memory during mental rotation is influenced by sex, menstrual cycle, and sex steroid hormones. Neuropsychologia, 45, 3203–3214.

    Article  PubMed  Google Scholar 

  • Seidenberg, M., Haltiner, A., Taylor, M. A., Hermann, B. B., & Wyler, A. (1994). Development and validation of a Multiple Ability Self-Report Questionnaire. Journal of Clinical and Experimental Neuropsychology, 16, 93–104.

    Article  CAS  PubMed  Google Scholar 

  • Silverman, D. H., Dy, C. J., Castellon, S. A., Lai, J., Pio, B. S., Abraham, L., et al. (2007). Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. Breast Cancer Research and Treatment, 103, 303–311.

    Article  CAS  PubMed  Google Scholar 

  • Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E., Johansen-Berg, H., et al. (2004). Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage, 23, S208–S219.

    Article  PubMed  Google Scholar 

  • Smith, S. M., Miller, K. L., Salimi-Khorshidi, G., Webster, M., Beckmann, C. F., Nichols, T. E., et al. (2011). Network modelling methods for FMRI. Neuroimage, 54(2), 875–891.

    Article  PubMed  Google Scholar 

  • Spielberger, C. D., Gorsuch, R. L., & Lushene, R. E. (1970). Manual for the state-trait anxiety inventory. Palo Alto: Consulting Psychologists Press.

    Google Scholar 

  • Troyer, A. K., & Rich, J. B. (2002). Psychometric properties of a new metamemory questionnaire for older adults. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 57, 19–27.

    Article  Google Scholar 

  • Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., et al. (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage, 15, 273–289.

    Article  CAS  PubMed  Google Scholar 

  • Unverzagt, F. W., Monahan, P. O., Moser, L. R., Zhao, Q., Carpenter, J. S., Sledge, G. W., Jr., et al. (2007). The Indiana University telephone-based assessment of neuropsychological status: a new method for large scale neuropsychological assessment. Journal of the International Neuropsychological Society, 13, 799–806.

    PubMed Central  PubMed  Google Scholar 

  • Von Ah, D., Harvison, K. W., Monahan, P. O., Moser, L. R., Zhao, Q., Carpenter, J. S., et al. (2009). Cognitive function in breast cancer survivors compared to healthy age- and education-matched women. Clinical Neuropsychology, 23, 661–674.

    Article  Google Scholar 

  • Wechsler, D. (2001). Wechsler Test of Adult Reading: WTAR. San Antonio: The Psychological Corporation.

    Google Scholar 

  • Wechsler, D. (2008). Wechsler adult intelligence scale (4th ed.). San Antonio: The Psychological Corporation.

    Google Scholar 

  • Wefel, J. S., & Schagen, S. B. (2012). Chemotherapy-related cognitive dysfunction. Current Neurology and Neuroscience Reports, 12, 267–275.

    Article  CAS  PubMed  Google Scholar 

  • Wefel, J. S., Saleeba, A. K., Buzdar, A. U., & Meyers, C. A. (2010). Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer, 116, 3348–3356.

    Article  PubMed  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. Lancet Oncology, 12, 703–708.

    Article  PubMed  Google Scholar 

  • Weinberger, D. A., & Schwartz, G. E. (1990). Distress and restraint as superordinate dimensions of self−reported adjustment: A typological perspective. Journal of Personality, 58, 381–417.

    Article  CAS  PubMed  Google Scholar 

  • White, T. (2003). Neuropsychological assessment battery. Lutz: Psychological Assessment Resources.

    Google Scholar 

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Authors and Affiliations

  1. Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Michiel B. de Ruiter & Sanne B. Schagen

  2. Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    Michiel B. de Ruiter

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  1. Michiel B. de Ruiter
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  2. Sanne B. Schagen
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Correspondence to Michiel B. de Ruiter.

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de Ruiter, M.B., Schagen, S.B. Functional MRI studies in non-CNS cancers. Brain Imaging and Behavior 7, 388–408 (2013). https://doi.org/10.1007/s11682-013-9249-9

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