Perko, M. | Search bioRxiv

bioRxiv2026

Traumatic Brain Injury Associated with Altered Corpus Callosum Microstructure in Females: Exploring the Roles of Menopause Timing and Hormone Therapy in UK Biobank

BackgroundTraumatic brain injury (TBI) has lasting effects on white matter, yet sex-specific factors such as menopause timing and hormone replacement therapy (HRT) may modulate these outcomes in females. ObjectivesTo investigate how TBI, menopause timing, HRT use, and reproductive history relate to corpus callosum white matter microstructure in female UK Biobank participants. DesignCross-sectional analysis of UK Biobank diffusion MRI data using propensity score matching to compare females with TBI to controls. MethodsWe analyzed diffusion MRI data from females with and without TBI. Corpus callosum fractional anisotropy (FA), mean diffusivity (MD), and isotropic volume fraction (ISOVF) were assessed. TBI effects were examined across pre- and post-menopausal groups, accounting for HRT use, duration, and reproductive factors. ResultsFemales with TBI (n=363) exhibited widespread corpus callosum alterations compared to propensity-matched controls (n=10,128), with reduced FA across all regions (genu: {beta}=-0.006, FDR p=0.027; body: {beta}=-0.006, FDR p=0.002; splenium: {beta}=-0.004, FDR p=0.009) and elevated MD in anterior regions (genu: FDR p=0.001; body: FDR p=0.002). TBI sustained before menopause was associated with significantly lower splenium FA ({beta}=-0.010, p=0.031) and higher body MD ({beta}=0.000019, p=0.021) compared with TBI sustained after menopause and controls. HRT use did not modify TBI-related alterations in primary analyses. However, among HRT users (n=3,108), a significant TBIxduration interaction emerged for genu MD ({beta}=2.00x10-6, p=0.0295), indicating that the effect of HRT duration on white matter microstructure differed between TBI cases and healthy females. Reproductive factors (parity, reproductive lifespan) independently predicted some white matter measures but did not confound TBI, menopause timing, or HRT associations. ConclusionsTBI-related white matter changes in females are influenced by menopause timing and hormonal exposure, with HRT effects dependent on duration and injury context. These findings highlight the importance of sex- and hormone-specific approaches in TBI research and the need for longitudinal studies to clarify mechanisms and potential interventions.

neuroscience↗

bioRxiv2025

The shifting dynamics of ancestry and culture at a post-Roman crossroads

The collapse of the western Roman Empire in the 5th century created a period of geopolitical upheaval, driven by Barbarians dispersing into the former Empire and reshaping post-Roman communities. While there is now evidence for a major genetic impact of these migrations into specific regions of Europe, it is unknown whether these changes in ancestry were uniform across the continent. We investigate present-day Slovenia, a crucial crossroad connecting the Roman East and West and the gate to Italy during the Langobard invasion. We conducted paleogenomic and isotopic analyses of 410 individuals from 21 sites across Slovenia and Cividale (Italy), establishing a longitudinal transect, spanning eight centuries. During Late Antiquity, despite changes in burial artifacts, kinship practices, and settlement structures reflecting a shift in culture, we find high levels of genetic continuity with the local Late Roman population and reduced mobility. However, demographic turnover began during the 8th century, when communities with northeastern European ancestry and distinct cultural practices entered the region, gradually advancing westward over the span of three centuries, replacing the local populations. This shows that cultural change in post-Roman Europe could be decoupled from genetic change in transit zones, demonstrating a dynamic spatiotemporal process across the continent.

genetics↗