Brain Structural and Functional Differences Between Long-Term High-Altitude Tibetan and Low-Altitude Han Residents: A
Chen ZhengJu1, G U Qiumei2, Sun Wei1
1Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular lmaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu,610041, China; Psychoradiology Key Laboratory of Sichuan Province, West China Hospital of Sichuan University. Chengdu, 610041, China; Xiamen Key Lab of Psychoradiology and Neuromodulation, Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian 361021, China.
Objective:
This study aimed to compare brain gray matter structure and resting-state brain activity between long-term high-altitude Tibetan residents and low-altitude Han residents using magnetic resonance imaging (MRI) and optically pumped magnetometer-based magnetoencephalography (OPM-MEG).
Methods:
Healthy adults residing long-term in either a high-altitude region (3,650 meters on average, n=32) or a low-altitude region (550 meters on average, n=32) were recruited. Analysis of voxel-based morphometry (VBM) on structural MRI was used to analyze volumetric differences between groups in human brain grey matter, including changes in whole gray matter volume (GMV), as well as changes in visual related regions. Resting-state brain activity was recorded using OPM-MEG. Power spectral density estimation, sensor-space phase-connectivity analysis, and source-space spectral-power analysis were performed to compare resting-state neural activity between the two groups.
Results:
Compared with the low‑altitude group, the high‑altitude group showed significantly larger GMV in widespread regions including the bilateral superior/middle frontal gyri, precentral gyrus, insula, thalamus, and multiple temporal, parietal and occipital areas (all t>3.00, FWE cluster‑corrected p < 0.05). In exploratory post hoc ROI analyses, the high-altitude group showed greater adjusted GMV across the 11 examined ROIs, with all group effects surviving Benjamini-Hochberg FDR correction. At the sensor level, the high‑altitude group exhibited robustly reduced gamma‑band (30-80 Hz) phase synchrony within posterior visual‑related sensors (PLI: Hedges' g = 1.29, uncorrected p=6.20 × 10-5, FDR-adjusted p = 0.0047). Directionally higher theta-band relative power was observed at the visual-region and whole-brain levels in the high-altitude group, but neither effect survived FDR correction. No significant group differences were found in other frequency bands or for absolute power measures.
Conclusion:
Long-term high-altitude Tibetan residents and low-altitude Han residents differed in regional GMV and visual-network oscillatory measures. Because residential altitude and ethnicity were completely collinear, these findings should be interpreted as between-group differences rather than altitude-specific causal effects.
