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ORIGINAL RESEARCH article

Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 16 - 2024 | doi: 10.3389/fnagi.2024.1421703

Evidence of compensatory neural hyperactivity in a subgroup of chemotherapy-treated breast cancer survivors and its association with brain aging

Provisionally accepted
Michele M Mulholland Michele M Mulholland 1Alexa Stuifbergen Alexa Stuifbergen 2Alexa De La Torre Schutz Alexa De La Torre Schutz 2Oscar Franco Rocha Oscar Franco Rocha 2Douglas W Blayney Douglas W Blayney 3Shelli Kesler Shelli Kesler 2*
  • 1 Michale E. Keeling Center for Comparative Medicine and Research, University of Texas MD Anderson Cancer Center, Bastrop, Louisiana, United States
  • 2 The University of Texas at Austin, Austin, United States
  • 3 Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, California, United States

The final, formatted version of the article will be published soon.

    Chemotherapy-related cognitive impairment (CRCI) remains poorly understood in terms of the mechanisms of cognitive decline. Neural hyperactivity has been reported on average in cancer survivors, but it is unclear which patients demonstrate this neurophenotype, limiting precision medicine in this population. We evaluated a retrospective sample of 80 breast cancer survivors and 80 non-cancer controls, age 35-73, for which we had previously identified and validated three data-driven, biological subgroups (biotypes) of CRCI. We measured neural activity using the z-normalized percent amplitude of fluctuation from resting state functional magnetic resonance imaging (MRI). We tested established, quantitative criteria to determine if hyperactivity can accurately be considered compensatory. We also calculated brain age gap by applying a previously validated algorithm to anatomic MRI. We found that neural activity differed across the three CRCI biotypes and controls (F = 13.5, p < 0.001), with Biotype 2 demonstrating significant hyperactivity compared to the other groups (p < 0.004, corrected), primarily in prefrontal regions. Alternatively, Biotypes 1 and 3 demonstrated significant hypoactivity (p < 0.02, corrected). Hyperactivity in Biotype 2 met several of the criteria to be considered compensatory. However, we also found a positive relationship between neural activity and brain age gap in these patients (r = 0.45, p = 0.042). Our results indicated that neural hyperactivity is specific to a subgroup of breast cancer survivors and, while it seems to support preserved cognitive function, it could also increase the risk of accelerated brain aging. These findings could inform future neuromodulatory interventions with respect to the risks and benefits of up or downregulation of neural activity.

    Keywords: fMRI, breast cancer, Brain aging, neural hyperactivity, Cognition

    Received: 22 Apr 2024; Accepted: 25 Nov 2024.

    Copyright: © 2024 Mulholland, Stuifbergen, De La Torre Schutz, Franco Rocha, Blayney and Kesler. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shelli Kesler, The University of Texas at Austin, Austin, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.