Altered white matter functional activity and connectivity in pretreatment breast cancer: exploratory associations...

Resting-state fMRI studies in breast cancer have predominantly focused on gray matter, with limited attention to white matter functional organization. This study investigated white matter functional activity and connectivity before treatment and their associations with anxiety and depressive symptoms.

Female patients with breast cancer (BC) were recruited from Zhejiang Provincial Tongde Hospital from November 2023 to December 2025. Amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) were used to compare local white matter functional activity between the BC and healthy control (HC) groups. Seed-based functional connectivity (FC) analysis was then performed to investigate whole-brain white matter FC alterations. Correlations between clinical scale scores and rs-fMRI indices were analyzed.

Compared with HCs, patients with BC showed altered ALFF/fALFF in the anterior and posterior corona radiata, internal capsule, posterior thalamic radiation, body of the corpus callosum, pontine crossing tract, left superior cerebellar peduncle, and left superior longitudinal fasciculus. Seed-based analysis revealed decreased FC within the bilateral anterior corona radiata and between the body of the corpus callosum and right anterior corona radiata, and increased FC between the left superior cerebellar peduncle and left posterior thalamic radiation. Higher ALFF in the body of the corpus callosum and reduced FC between this region and the right anterior corona radiata were associated with higher Hamilton Anxiety Rating Scale scores at an uncorrected threshold. Neither association survived FDR correction.

Patients with BC showed altered white matter functional activity and connectivity before cancer-related treatment, suggesting that pretreatment brain functional alterations may also involve white matter functional organization. The relationship between these white matter changes and anxiety or depressive symptoms remains exploratory.