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Brain gray matter (GM) reductions have been reported after breast cancer chemotherapy, typically in small and/or cross-sectional cohorts, most commonly using voxel-based morphometry (VBM). There has been little examination of approaches such as deformation-based morphometry (DBM), machine-learning-based brain aging metrics, or the relationship of clinical and demographic risk factors to GM reduction. This international data pooling study begins to address these questions. Participants included breast cancer patients treated with (CT+, n = 183) and without (CT-, n = 155) chemotherapy and noncancer controls (NC, n = 145), scanned pre- and post-chemotherapy or comparable intervals. VBM and DBM examined GM volume. Estimated brain aging was compared to chronological aging. Correlation analyses examined associations between VBM, DBM, and brain age, and between neuroimaging outcomes, baseline age, and time since chemotherapy completion. CT+ showed longitudinal GM volume reductions, primarily in frontal regions, with a broader spatial extent on DBM than VBM. CT- showed smaller clusters of GM reduction using both methods. Predicted brain aging was significantly greater in CT+ than NC, and older baseline age correlated with greater brain aging. Time since chemotherapy negatively correlated with brain aging and annual GM loss. This large-scale data pooling analysis confirmed findings of frontal lobe GM reduction after breast cancer chemotherapy. Milder changes were evident in patients not receiving chemotherapy. CT+ also demonstrated premature brain aging relative to NC, particularly at older age, but showed evidence for at least partial GM recovery over time. When validated in future studies, such knowledge could assist in weighing the risks and benefits of treatment strategies., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Several studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as "chemobrain", is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remain poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. Mediation analysis showed that the functional connectivity alteration pattern is a separable treatment symptom from the decreased cognitive health. Current study indicates that more targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Neural dysfunction and cognitive complaints are associated with chemotherapy for breast cancer although trajectory and contributory factors remain unclear. We prospectively examined neurocognition using fMRI and self-reported cognitive, physical and psychological symptoms in women treated with adjuvant chemotherapy over one year. Patients treated with (n = 28) or without (n = 34) chemotherapy for localized breast cancer and healthy controls (n = 30) performed a Verbal Working Memory Task (VWMT) during fMRI and provided self-reports at baseline (pre-adjuvant treatment), five- (M5) and 12-months (M12). Repeated measures ANOVA and multivariable regression determined change over time and possible predictors (e.g., hemoglobin, physical symptoms, worry) of VWMT performance, fMRI activity in the frontoparietal executive network, and cognitive complaints at M12. Trajectories of change in VWMT performance for chemotherapy and healthy control groups differed significantly with the chemotherapy group performing worse at M12. Chemotherapy patients had persistently higher spatial variance (neural inefficiency) in executive network fMRI-activation than both other groups from baseline to M12. Cognitive complaints were similar among groups over time. At M12, VWMT performance and executive network spatial variance were each independently predicted by chemotherapy treatment and their respective baseline values, while cognitive complaints were predicted by baseline level, physical symptoms and worry. Executive network inefficiency and neurocognitive performance deficits pre-adjuvant treatment predict cognitive dysfunction one-year post-baseline, particularly in chemotherapy-treated patients. Persistent cognitive complaints are linked with physical symptom severity and worry regardless of treatment. Pre-chemotherapy interventions should target both neurocognitive deficits and symptom burden to improve cognitive outcomes for breast cancer survivors.

Stressful life events are related to negative outcomes, including physical and psychological manifestations of distress, and behavioral deficits. Patients diagnosed with breast cancer report impaired attention and working memory prior to adjuvant therapy, which may be induced by distress. In this article, we examine whether brain dynamics show systematic changes due to the distress associated with cancer diagnosis. We hypothesized that impaired working memory is associated with suppression of "long-memory" neuronal dynamics; we tested this by measuring scale-free ("fractal") brain dynamics, quantified by the Hurst exponent (H). Fractal scaling refers to signals that do not occur at a specific time-scale, possessing a spectral power curve P(f)∝ f(-β); they are "long-memory" processes, with significant autocorrelations. In a BOLD functional magnetic resonance imaging study, we scanned three groups during a working memory task: women scheduled to receive chemotherapy or radiotherapy and aged-matched controls. Surprisingly, patients' BOLD signal exhibited greater H with increasing intensity of anticipated treatment. However, an analysis of H and functional connectivity against self-reported measures of psychological distress (Worry, Anxiety, Depression) and physical distress (Fatigue, Sleep problems) revealed significant interactions. The modulation of (Worry, Anxiety) versus (Fatigue, Sleep Problems, Depression) showed the strongest effect, where higher worry and lower fatigue was related to reduced H in regions involved in visuospatial search, attention, and memory processing. This is also linked to decreased functional connectivity in these brain regions. Our results indicate that the distress associated with cancer diagnosis alters BOLD scaling, and H is a sensitive measure of the interaction between psychological versus physical distress., (© 2014 Wiley Periodicals, Inc.)

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.

Unlabelled: [Correction Notice: An Erratum for this article was reported in Vol 33(3) of Health Psychology (see record 2014-07787-001). The name of author Misook Jung was misspelled as Mi Sook Jung. All versions of this article have been corrected.], Objective: Altered cognitive function has been associated with breast cancer treatment, particularly adjuvant chemotherapy, but the underlying neuropsychological mechanisms are not yet understood. Recent research indicates that compromised attention and working memory can exist before adjuvant treatment, implicating psychological distress, such as worry, as a possible contributor to observed alterations in cognitive function. We hypothesized that worry associated with breast cancer diagnosis might influence neurocognitive responses before any adjuvant therapy., Design: Fifty women, 25 due to receive chemotherapy and 25 due to receive radiation therapy, participated in the study. Women performed a verbal working memory task during functional magnetic resonance imaging scanning to assess neurocognitive responses before any adjuvant treatment and to test the relationship of such responses with self-reports of worry., Results: Although prechemotherapy participants showed significantly higher levels of worry compared with preradiation participants, higher worry, across both groups, was related to altered brain function. Specifically, increased worry was associated with reduced demand-related deactivation in default-mode regions, such as the precuneus/posterior cingulate. Reduced demand-related deactivation was critically related to worse behavioral performance, which was partially mediated by worry., Conclusion: Worry appears to be a significant contributor to neurocognitive dysfunction independent of adjuvant treatment for breast cancer. These results suggest that alterations in cognitive function may develop before any chemotherapy treatment and that worry about cancer diagnosis may contribute to reports of "chemo brain" during treatment. Psychological interventions aimed at mitigating worry may help to alleviate cognitive dysfunction associated with life-threatening illness such as breast cancer., (PsycINFO Database Record (c) 2014 APA, all rights reserved.)

Despite clinical reports of cognitive deficits associated with cancer chemotherapy, the underlying brain mechanisms are not clear. This research examined selective attention and working memory using functional magnetic resonance imaging (fMRI) in women before chemotherapy for localized breast cancer. Patients were tested with an established selective attention and working memory task during fMRI. Compared with healthy controls, patients showed (a) bilateral brain activation in high-demand task conditions with recruitment of additional components of attention/working memory circuitry, and (b) less accurate and slower task performance. Results indicate compromised cognitive functioning before any chemotherapy and raise key questions for further research.