Longitudinal Functional Magnetic Resonance Imaging of Brain Activity, Connectivity, and Behavior in Breast Cancer Survivors Following Chemotherapy

<b><i>Background:</i></b> Chemotherapy-related cognitive impairment (CRCI), commonly known as "chemobrain," frequently occurs during breast cancer treatment and has been linked to altered brain function. This resting-state functional magnetic resonance imaging study examined chemotherapy-related changes in functional brain activity, network connectivity, and associations with cognitive outcomes. <b><i>Methods:</i></b> Twenty-eight patients with breast cancer were assessed prechemotherapy (BB) and postchemotherapy (BBF), alongside 27 healthy controls of comparable age at baseline (BH) and follow-up (BHF). Mean fractional amplitude of low-frequency fluctuations (mfALFF) and mean regional homogeneity (mReHo) quantified functional brain activity. Graph theoretical analysis (GTA) assessed network topology; network-based statistics (NBS) evaluated interregional connectivity. Cognitive performance was evaluated through standardized assessments. <b><i>Results:</i></b> Postchemotherapy patients exhibited reduced anxiety and lower FACT-Cog scores. Voxel-wise analyses showed increased mfALFF in frontal regions and mReHo in superior temporal and inferior frontal gyri, alongside decreases in postcentral, lingual, and parahippocampal areas. Healthy controls showed increased activity in medial frontal and cingulate regions, with reductions in the temporal lobe and putamen. GTA revealed higher global efficiency and reduced modularity, path length, and network complexity in the BBF group compared with BHF. NBS showed weaker structural connectivity in motor and occipital regions prechemotherapy and decreased parietal and insular connectivity postchemotherapy. Multiple regression showed brain-behavior correlations: declines in FACT-Cog, Digit Symbol Substitution, and mood scores were linked to altered activity in frontal, parietal, cingulate, and occipital areas, while positive correlations suggested compensatory activation. <b><i>Conclusions:</i></b> Chemotherapy was associated with longitudinal alterations in brain activity, network organization, and connectivity in breast cancer survivors. Brain-behavior associations suggest disrupted neural networks may underlie CRCI.