Exploratory analysis of high-altitude effects on brain morphology and myelination in native Tibetan infants

Background: High-altitude environments present unique challenges to brain adaptability. This study aimed to explore the brain magnetic resonance imaging (MRI) characteristics of neurologically normal Tibetan neonates, and to compare brain volumes and myelination status across different altitude levels. Methods: This was a case-control exploratory study. A total of 30 neurologically normal infants in the high-altitude group (altitude: 3,650 m) and a total of 30 neurologically normal infants in the sea-level group (altitude: 4 m) were included in the study. The infants in the two groups were matched 1:1 using propensity score matching (PSM) for gestational age at birth, birth weight, sex, and postnatal age at MRI examination. The primary outcomes were differences in volumetrically segmented tissue (lateral ventricles, gray matter, and white matter) and intracranial volume (ICV) between the two groups. We further compared the differences among altitude subgroups. Myelination status was also assessed using the T1-weighted/T2-weighted (T1w/T2w) ratio. Results: Compared with the sea-level group, ICV was significantly increased in the high-altitude group, an increase that appeared to be primarily attributable to larger gray matter and lateral ventricular volumes. The T1w/T2w ratio in the middle cerebellar peduncle (MCP) was significantly lower in the high-altitude group than the sea-level group. In the altitude subgroup analysis, ICV was found to be significantly increased in altitude subgroup 2 (4,000-4,800 m) but not in altitude subgroup 1 (3,500-4,000 m). Conclusions: ICV was significantly increased in the high-altitude group compared to the sea-level group, especially in altitude areas above 4,000 m. Additionally, delayed myelination in the MCP was observed in the high-altitude group.