Prospective evaluation of functional brain activity and oxidative damage in breast cancer: changes in task-induced deactivation during a working memory task

Abstract

Cancer-related cognitive dysfunction is an important issue for breast cancer survivors. Previous research has identified both cross-sectional and longitudinal alterations in brain function related to cancer status and treatment. In this study, we prospectively collected functional magnetic resonance imaging data in breast cancer cases treated with adjuvant chemotherapy and in controls with no cancer history during a working memory task. Data and blood specimens were collected immediately prior to the start of treatment (baseline) and following completion of treatment (follow-up), and at yoked intervals for controls. In secondary analysis we assessed the levels of oxidative DNA damage in peripheral blood lymphocytes of cases and controls using the Comet assay. A significant group*time interaction revealed reduced deactivation in the superior frontal gyrus in the controls at follow-up, in contrast to cases, who exhibited similar magnitude of deactivation at baseline and follow-up. Working memory performance indicated a significant improvement in the controls at follow-up, and no change in performance in cases. In secondary analyses, oxidative DNA damage levels were elevated in the cases at follow-up compared to controls, but no associations were found between the Comet assay variables and functional imaging at either time-point or group. In light of previous reports on task induced deactivations, our findings reflect continuing effortful processing at follow-up in the breast cancer group, with relatively less effortful processing in the control group given the reduced novelty and practice effects from the baseline to follow-up.

Keywords: Cancer; Working memory; fMRI.

Figure 1.

The number above each slice indicates the MNI z coordinate. Warm colors indicate increased activation while cool colors indicate decreased activation for the breast cancer versus healthy control group. a) Group x Time interaction in superior medial frontal gyrus and superior frontal gyrus for the 3-back condition; b) for cases, no significant change in recruitment for the 3-back condition; c) for controls, significantly decreased task induced deactivation in medial and superior frontal gyrus at follow-up compared to baseline for the 3-back condition; d) parametric weighting of 0, 1, 2, 3 back and associated task induced deactivations to contextualize changes in task-induced deactivation with increasing working memory load from 0- to 3-back conditions; e) BOLD signal magnitudes for cases and controls from baseline to follow-up in superior frontal gyrus (21 63 24); f) Endonuclease III Treated Tail Intensity (TIEndoIII) minus endogenous damage for cases and controls from baseline to follow-up; AU, arbitrary units.