Skip to main content

Advertisement

SpringerLink
Log in

Subjective cancer-related cognitive impairments and salience network connectivity in breast cancer survivors

  • Published:
Journal of Cancer Survivorship Aims and scope Submit manuscript

Abstract

Purpose

Little is known about the neural basis of subjective cancer-related cognitive changes. The purpose of this study was to explore salience network connectivity in relation to subjective executive and memory dysfunction in breast cancer survivors compared to controls.

Methods

A retrospective cross-sectional analysis of neuroimaging, subjective cognitive, clinical, and demographic data in chemotherapy-treated primary breast cancer survivors compared to frequency matched controls was used. Functional connectivity within salience network hubs (anterior cingulate, bilateral insula) was determined using resting state functional MRI. Mann–Whitney U tests were used to evaluate group differences and Spearman’s rho correlations were examined among the behavioral measures and salience network connectivity.

Results

We included 65 breast cancer survivors and 71 controls. Survivors demonstrated greater subjective executive dysfunction and memory complaints (p < .001) and lower salience network connectivity (p < .05) than controls. Executive functioning correlated with bilateral insula and left anterior cingulate connectivity (rho >  − 0.29, p < .05). Distress did not correlate with salience network connectivity.

Conclusion

These findings suggest that salience network connectivity may represent a biomarker of subjective cancer-related cognitive changes.

Implications for Cancer Survivors

Subjective cancer-related cognitive changes are common following treatment and associated with objective changes in brain connectivity

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

The original MRI data underlying this article cannot be shared publicly due to data protection regulation, but connectome matrices are available upon request to the corresponding author (srkesler@austin.utexas.edu). All preprocessing and analysis codes are available at https://github.com/srkesler.

Abbreviations

CAD:

Clinical Assessment of Depression

CRCI:

Cancer-related cognitive impairments

fMRI:

Functional magnetic resonance imaging

GEC:

Behavioral Rating Inventory of Executive Function General Executive Composite score

References

  1. Lange M, Joly F, Vardy J, Ahles T, Dubois M, Tron L, Winocur G, De Ruiter MB, Castel H. Cancer-related cognitive impairment: an update on state of the art, detection, and management strategies in cancer survivors. Ann Oncol. 2019;30(12):1925–40.

    Article  CAS  PubMed  Google Scholar 

  2. Selamat MH, Loh SY, Mackenzie L, Vardy J. Chemobrain experienced by breast cancer survivors: a meta-ethnography study investigating research and care implications. PLoS One. 2014;9(9):e108002.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Porro B, Durand MJ, Petit A, Bertin M, Roquelaure Y. Return to work of breast cancer survivors: toward an integrative and transactional conceptual model. J Cancer Surviv. 2021;16(3):590–603.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mayo SJ, Lustberg M, Dhillon HM, Nakamura ZM, Allen DH, Von ah D, Janelsins MC, Chan A, Olson K, Tan CJ, Toh YL, Oh J, Grech L, Cheung YT, Subbiah IM, Petranovic D, D’Olimpio J, Gobbo M, Koeppen S, Loprinzi CL, Pang L, Shinde S, Ntukidem O, Peters KB. Cancer-related cognitive impairment in patients with non-central nervous system malignancies: an overview for oncology providers from the MASCC Neurological Complications Study Group. Support Care Cancer. 2021;29(6):2821–40.

    Article  PubMed  Google Scholar 

  5. Bray VJ, Dhillon HM, Vardy JL. Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment. J Cancer Surviv. 2018;12(4):537–59.

    Article  PubMed  Google Scholar 

  6. Hutchinson AD, Hosking JR, Kichenadasse G, Mattiske JK, Wilson C. Objective and subjective cognitive impairment following chemotherapy for cancer: a systematic review. Cancer Treat Rev. 2012;38(7):926–34.

    Article  PubMed  Google Scholar 

  7. Wefel JS, Kesler SR, Noll KR, Schagen SB. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA Cancer J Clin. 2015;65(2):123–38.

    Article  PubMed  Google Scholar 

  8. Kaiser J, Bledowski C, Dietrich J. Neural correlates of chemotherapy-related cognitive impairment. Cortex. 2014;54:33–50.

    Article  PubMed  Google Scholar 

  9. Simo M, Rifa-Ros X, Rodriguez-Fornells A, Bruna J. Chemobrain: a systematic review of structural and functional neuroimaging studies. Neurosci Biobehav Rev. 2013;37(8):1311–21.

    Article  PubMed  Google Scholar 

  10. Kesler S, Janelsins M, Koovakkattu D, Palesh O, Mustian K, Morrow G, Dhabhar FS. Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain Behav Immun. 2013;30(Suppl):S109–16.

    Article  CAS  PubMed  Google Scholar 

  11. Kesler SR. Prevalence of cerebral small-vessel disease in long-term breast cancer survivors exposed to both adjuvant radiotherapy and chemotherapy. Breast Diseases: A Year Book Quarterly. 2015;26(4):353.

    Google Scholar 

  12. Correa DD, Ahles TA. Neurocognitive changes in cancer survivors. Cancer J. 2008;14(6):396–400.

    Article  PubMed  Google Scholar 

  13. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. Lancet Oncol. 2011;12(7):703–8.

    Article  PubMed  Google Scholar 

  14. Janelsins MC, Kohli S, Mohile SG, Usuki K, Ahles TA, Morrow GR. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2011;38(3):431–8.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Vardy J. Cognitive function in breast cancer survivors. Cancer Treat Res. 2009;151:387–419.

    Article  PubMed  Google Scholar 

  16. Wefel JS, Saleeba AK, Buzdar AU, Meyers CA. Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. Cancer. 2010;116(14):3348–56.

    Article  PubMed  Google Scholar 

  17. Jansen CE, Miaskowski C, Dodd M, Dowling G, Kramer J. A metaanalysis of studies of the effects of cancer chemotherapy on various domains of cognitive function. Cancer. 2005;104(10):2222–33.

    Article  PubMed  Google Scholar 

  18. McDonald BC, Conroy SK, Smith DJ, West JD, Saykin AJ. Frontal gray matter reduction after breast cancer chemotherapy and association with executive symptoms: a replication and extension study. Brain Behav Immun. 2013;30(Suppl):S117–25.

    Article  PubMed  Google Scholar 

  19. Kesler SR, Kent JS, O’Hara R. Prefrontal cortex and executive function impairments in primary breast cancer. Arch Neurol. 2011;68(11):1447–53.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Askren MK, Jung M, Berman MG, Zhang M, Therrien B, Peltier S, Ossher L, Hayes DF, Reuter-Lorenz PA, Cimprich B. Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation. Breast Cancer Res Treat. 2014;147(2):445–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Apple AC, Schroeder MP, Ryals AJ, Wagner LI, Cella D, Shih PA, Reilly J, Penedo FJ, Voss JL, Wang L. Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy. NeuroImage Clin. 2018;20:110–8.

    Article  PubMed  PubMed Central  Google Scholar 

  22. S.R. Kesler, T. Tang, A.M. Henneghan, M. Wright, M.W. Gaber, O. Palesh, Cross-sectional characterization of local brain network connectivity pre and post breast cancer treatment and distinct association with subjective cognitive and psychological function, Frontiers in neurology 12(1969) (2021).

  23. Kesler SR, Wefel JS, Hosseini SM, Cheung M, Watson CL, Hoeft F. Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls. Proc Natl Acad Sci USA. 2013;110(28):11600–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dumas JA, Makarewicz J, Schaubhut GJ, Devins R, Albert K, Dittus K, Newhouse PA. Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study. Brain Imaging Behav. 2013;7(4):524–32.

    Article  PubMed  Google Scholar 

  25. Zeng Y, Cheng ASK, Song T, Sheng X, Zhang Y, Liu X, Chan CCH. Subjective cognitive impairment and brain structural networks in Chinese gynaecological cancer survivors compared with age-matched controls: a cross-sectional study. BMC Cancer. 2017;17(1):796.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chand GB, Wu J, Hajjar I, Qiu D. Interactions of the salience network and its subsystems with the default-mode and the central-executive networks in normal aging and mild cognitive impairment. Brain Connectivity. 2017;7(7):401–12.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Seeley WW. The salience network: a neural system for perceiving and responding to homeostatic demands. J Neurosci. 2019;39(50):9878–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chong JSX, Ng GJP, Lee SC, Zhou J. Salience network connectivity in the insula is associated with individual differences in interoceptive accuracy. Brain Struct Funct. 2017;222(4):1635–44.

    Article  PubMed  Google Scholar 

  29. Roth RM, Lance CE, Isquith PK, Fischer AS, Giancola PR. Confirmatory factor analysis of the behavior rating inventory of executive function-adult version in healthy adults and application to attention-deficit/hyperactivity disorder. Arch Clin Neuropsychol. 2013;28(5):425–34.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Troyer AK, Rich JB. Psychometric Properties of a New Metamemory Questionnaire for Older Adults. J Gerontol B Psychol Sci Soc Sci. 2002;57(1):P19–27.

    Article  PubMed  Google Scholar 

  31. AAghakhani EK Chan Test Reviews: Bracken BA, Howell K 2004. Clinical Assessment of Depression Odessa, FL: Psychological Assessment Resources. J Psychoeduc Assess. 2007;25(4):416–22.

    Article  Google Scholar 

  32. Glover GH, Lai S. Self-navigated spiral fMRI: interleaved versus single-shot. Magn Reson Med. 1998;39(3):361–8.

    Article  CAS  PubMed  Google Scholar 

  33. Ashburner J. SPM: a history. Neuroimage. 2012;62(2):791–800.

    Article  PubMed  Google Scholar 

  34. Whitfield-Gabrieli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connectivity. 2012;2(3):125–41.

    Article  PubMed  Google Scholar 

  35. Behzadi Y, Restom K, Liau J, Liu TT. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage. 2007;37(1):90–101.

    Article  PubMed  Google Scholar 

  36. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15(1):273–89.

    Article  CAS  PubMed  Google Scholar 

  37. Van der Gucht K, Ahmadoun S, Melis M, de Cloe E, Sleurs C, Radwan A, Blommaert J, Takano K, Vandenbulcke M, Wildiers H, Neven P, Kuppens P, Raes F, Smeets A, Sunaert S, Deprez S. Effects of a mindfulness-based intervention on cancer-related cognitive impairment: results of a randomized controlled functional magnetic resonance imaging pilot study. Cancer. 2020;126(18):4246–55.

    Article  PubMed  Google Scholar 

  38. R.M. Roth, P.K. Isquith, G. Gioia, Behavioral rating inventory of executive function - adult version, Psychological Assessment Resources, Lutz, FL, 2005.

  39. Friedman NP, Robbins TW. The role of prefrontal cortex in cognitive control and executive function. Neuropsychopharmacol. 2022;47(1):72–89.

    Article  Google Scholar 

  40. Menon V, D’Esposito M. The role of PFC networks in cognitive control and executive function. Neuropsychopharmacol. 2022;47(1):90–103.

    Article  Google Scholar 

  41. Bernstein LJ, Edelstein K, Sharma A, Alain C. Chemo-brain: an activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies. Neurosci Biobehav Rev. 2021;130:314–25.

    Article  CAS  PubMed  Google Scholar 

  42. Gratton C, Sun H, Petersen SE. Control networks and hubs. Psychophysiol. 2018;55(3):e13032.

  43. Hou J, Song B, Chen ACN, Sun C, Zhou J, Zhu H, Beauchaine TP. Review on neural correlates of emotion regulation and music: implications for emotion dysregulation. Front Psychol. 2017;8:501.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Conley CC, Bishop BT, Andersen BL. Emotions and emotion regulation in breast cancer survivorship. Healthcare (Basel). 2016;4(3):56.

    Article  PubMed  Google Scholar 

  45. Arndt J, Das E, Schagen SB, Reid-Arndt SA, Cameron LD, Ahles TA. Broadening the cancer and cognition landscape: the role of self-regulatory challenges. Psychooncol. 2014;23(1):1–8.

    Article  Google Scholar 

  46. Flavell JH. Metacognition and cognitive monitoring: a new area of cognitive-developmental inquiry. Am Psychol. 1979;34(10):906–11.

    Article  Google Scholar 

  47. Vaccaro AG, Fleming SM. Thinking about thinking: a coordinate-based meta-analysis of neuroimaging studies of metacognitive judgements. Brain Neurosci Adv. 2018;2:2398212818810591.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Perrier J, Joue G, Desgranges B, Allouache D, Levy C, Noal S, Dayan J, Eustache F, Joly F, Viard A, Giffard B. Self-referential processes and resting-state connectivity in breast cancer patients before and 1 year after chemotherapy. Eur J Neurosci. 2022;55(2):624–36.

    Article  CAS  PubMed  Google Scholar 

  49. Sha Z, Wager TD, Mechelli A, He Y. Common dysfunction of large-scale neurocognitive networks across psychiatric disorders. Biol Psychiatry. 2019;85(5):379–88.

    Article  PubMed  Google Scholar 

  50. Kesler SR, Wayfull JS, Hosseini SM, Cheung M, Watson CL, Hoeft F. Default mode network connectivity distinguishes chemotherapy-treated breast cancer survivors from controls. Proc Natl Acad Sci USA. 2013;110(28):11600–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Sharma N, Murari G, Vandermorris S, Verhoeff N, Herrmann N, Chen JJ, Mah L. Functional connectivity between the posterior default mode network and parahippocampal gyrus is disrupted in older adults with subjective cognitive decline and correlates with subjective memory ability. J Alzheimer’s Disease : JAD. 2021;82(1):435–45.

    Article  PubMed  Google Scholar 

  52. Costa DSJ, Fardell JE. Why are objective and perceived cognitive function weakly correlated in patients with cancer? J Clin Oncol. 2019;37(14):1154–8.

    Article  PubMed  Google Scholar 

  53. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. Int Rev Psychiatry. 2014;26(1):102–13.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all of the breast cancer survivors and other volunteers who were a part of this study.

Funding

This work was supported by the National Institutes of Health (K01NR018970, 2020–2023; 1R01CA226080, 2019–2025; 2R01CA172145, 2012–2023; 1DP2OD004445, 2008–2013).

Author information

Authors and Affiliations

  1. School of Nursing, University of Texas at Austin, 1710 Red River St, D0100, Austin, TX, 78712, USA

    Ashley M. Henneghan & Shelli R. Kesler

  2. Department of Oncology, Dell School of Medicine, University of Texas at Austin, Austin, TX, 78712, USA

    Ashley M. Henneghan & Shelli R. Kesler

  3. Department of Diagnostic Medicine, Dell School of Medicine, University of Texas at Austin, Austin, TX, 78712, USA

    Shelli R. Kesler

Authors
  1. Ashley M. Henneghan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shelli R. Kesler
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Shelli Kesler. The first draft of the manuscript was written by Shelli Kesler and Ashley Henneghan and both authors commented on previous versions of the manuscript. Both authors read and approved the final manuscript.

Corresponding author

Correspondence to Shelli R. Kesler.

Ethics declarations

Ethics approval

All study procedures were approved and overseen by the Stanford University Institutional Review Board.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Conflict of interests

The authors declare no conflict of interest.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Henneghan, A.M., Kesler, S.R. Subjective cancer-related cognitive impairments and salience network connectivity in breast cancer survivors. J Cancer Surviv 17, 967–973 (2023). https://doi.org/10.1007/s11764-022-01307-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11764-022-01307-8

Keywords

Search

Navigation