LAUSR

Numerous differences between males and females in brain organization have been described including in the development, performance, and lateralization of language function. However, there is very limited knowledge of whether language processing differs across sex in patients with brain lesions. In particular, malignant brain tumors (MBT) demonstrate significant sex differences in incidence and long-term survival. Given the importance of brain organization and planning surgical treatment for patients with brain tumors, we investigated the effect of sex on the organization of language in a cohort of patients with MBT. In the current study, we carried out a retrospective analysis in 47 patients with MBT (22 females, 25 males), retrieving their clinical characteristics and task-based and resting-state functional magnetic resonance image (fMRI) data from our clinical database. General Linear Model (GLM) and region-of-interest (ROI) based resting-state functional connectivity (RSFC) analyses were applied to explore the effect of sex on language tasks associated activations and functional connectivity. Across the Sentence Completion task and Antonym Generation task, female patients showed greater activation volumes in the left inferior frontal gyrus, right precuneus, and left superior parietal lobule, while male patients showed larger clusters of activation of the left supplemental motor area (SMA), left inferior parietal lobule (IPL), left precuneus, bilateral precentral gyrus, and right supramarginal gyrus (SMG). Furthermore, the left SMA was a highly sex-specific brain area during the language performance, and it showed stronger resting-state correlations with brain areas within the intrinsic language network in females, while it showed stronger resting-state connections with brain areas involving the visuomotor/higher level cognitive functions in males. These findings enhance our understanding of the role of sex in language organization in patients with MBT, helping neurosurgeons assess surgical risk and plan surgery in patients with MBT to best preserve language function.