Longitudinal changes in DMN Connectivity following chemotherapy in Breast Cancer

Purpose: Women treated for breast cancer often experience cognitive complaints. We studied whether longitudinal changes in resting state functional connectivity from pre-treatment to shortly after chemotherapy could possibly underlie these cognitive complaints. Methods: Fifteen women with early-stage breast cancer scheduled to receive adjuvant chemotherapy underwent resting state fMRI (rs-fMRI) before the start of therapy (t1) and 4 to 6 months after treatment (t2). Fourteen women with early-stage breast cancer who did not receive chemotherapy and 17 matched healthy controls underwent rs-fMRI at matched intervals. Images were preprocessed and warped to MNI space using SPM. Regions within the default mode network (DMN) and frontoparietal network (FPN), both linked with cognitive impairment, were defined as spherical regions of interest (ROIs) around literature-based MNI coordinates1. The functional connectivity was assessed calculating the partial correlations between the different regions within each network. We used one-way ANOVA and paired t-test to examine differences between groups at baseline and changes overtime within groups. A correlation analysis was performed to link the functional connectivity results to the subjective cognitive complaints (CFQ). All analyses were Bonferroni-corrected for multiple comparisons. Results: Paired t-test revealed significantly increased (p<.05) connectivity from t1 to t2 in the chemotherapy-treated group between the right inferior temporal gyrus (ITG) and anterior medio prefrontal cortex (MPFC) of the DMN. This increase, however, did not correlate with the subjective complaints. In the FPN no significant results were found after Bonferroni-correction. At baseline, no differences were found between chemotherapy-treated patients and controls. This result was not influenced by the inclusion of depression scores. Conclusion: Our findings provide evidence for longitudinal changes in DMN connectivity following chemotherapy-treatment. This might reflect underlying neurotoxic changes in the brain. Future research will add DTI fiber tractography to study possible related white matter microstructural changes.status: accepte