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Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation

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Abstract

The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.

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Abbreviations

ADHD:

Attention deficit hyperactivity disorder

AFI:

Attentional function index

ANOVA:

Analysis of variance

DCIS:

Ductal carcinoma in situ

EN:

Executive network

FACIT-F:

Functional assessment of chronic illness therapy-fatigue

fMRI:

Functional magnetic resonance imaging

g/dl:

Grams/deciliter

Hb:

Hemoglobin

MMSE:

Mini-mental state exam

ms:

Milliseconds

PHQ:

Patient health questionnaire

TIWI:

Three-item worry index

VWMT:

Verbal working memory task

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Acknowledgments

This study was supported by the National Institutes of Health R01 NR01039 (BC), and the Fashion Footwear Charitable Foundation of New York/QVC Presents Shoes on Sale™ (DFH).

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Authors and Affiliations

  1. Integrated Brain Imaging Center, Department of Radiology, University of Washington, Seattle, USA

    Mary K. Askren

  2. University of Michigan, Ann Arbor, USA

    Misook Jung, Min Zhang, Barbara Therrien, Scott Peltier, Lynn Ossher, Daniel F. Hayes, Patricia A. Reuter-Lorenz & Bernadine Cimprich

  3. Chungnam National University, Daejeon, Korea

    Misook Jung

  4. University of Chicago, Chicago, USA

    Marc G. Berman

Authors
  1. Mary K. Askren
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  2. Misook Jung
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  4. Min Zhang
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  5. Barbara Therrien
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  7. Lynn Ossher
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  9. Patricia A. Reuter-Lorenz
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  10. Bernadine Cimprich
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Corresponding author

Correspondence to Mary K. Askren.

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Askren, M.K., Jung, M., Berman, M.G. et al. Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation. Breast Cancer Res Treat 147, 445–455 (2014). https://doi.org/10.1007/s10549-014-3092-6

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  • DOI: https://doi.org/10.1007/s10549-014-3092-6

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