Structural modifications of the brain in acclimatization to high-altitude

Abstract

Adaptive changes in respiratory and cardiovascular responses at high altitude (HA) have been well clarified. However, the central mechanisms underlying HA acclimatization remain unclear. Using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) with fractional anisotropy (FA) calculation, we investigated 28 Han immigrant residents (17-22 yr) born and raised at HA of 2616-4200 m in Qinghai-Tibetan Plateau for at least 17 years and who currently attended college at sea-level (SL). Their family migrated from SL to HA 2-3 generations ago and has resided at HA ever since. Control subjects were matched SL residents. HA residents (vs. SL) showed decreased grey matter volume in the bilateral anterior insula, right anterior cingulate cortex, bilateral prefrontal cortex, left precentral cortex, and right lingual cortex. HA residents (vs. SL) had significantly higher FA mainly in the bilateral anterior limb of internal capsule, bilateral superior and inferior longitudinal fasciculus, corpus callosum, bilateral superior corona radiata, bilateral anterior external capsule, right posterior cingulum, and right corticospinal tract. Higher FA values in those regions were associated with decreased or unchanged radial diffusivity coinciding with no change of longitudinal diffusivity in HA vs. SL group. Conversely, HA residents had lower FA in the left optic radiation and left superior longitudinal fasciculus. Our data demonstrates that HA acclimatization is associated with brain structural modifications, including the loss of regional cortical grey matter accompanied by changes in the white matter, which may underlie the physiological adaptation of residents at HA.

Figure 1. Gray matter volume decrease in HA residents vs. SL controls.

(A) A statistical parametric map for gray matter reduced in HA residents compared with SL controls (B) Axial slice series depicting regions showing reduced gray matter volume in HA residents overlaid on Talairach template. Display threshold was set at |t|>2.70, p<0.01 (FWE corrected). Detailed coordinate and cluster size information of significant regions were shown in Table 3.

Figure 2. Statistical maps of group comparison of FA values on a voxel-wise basis (results of TBSS).

The group's mean FA skeleton (green) was overlaid on the mean FA images. The threshold of mean FA skeleton was set at 0.2. (A–H) show significantly higher FA value (red to yellow) and (I and J) show significantly lower FA value (blue) in HA residents than SL controls at p<0.05. Detailed coordinate and cluster size information of significant regions (higher FA: clusters >100 voxels; lower FA: clusters >8 voxels) were shown in Table 5.

Figure 3. Examples of ROI demarcation on FA images.

CC: Corpus callosum; PFWM: Prefrontal white matter; TLWM: Temporal lobe white matter; OLWM: Occipital lobe white matter; IC: Internal capsule; EC: External capsule. The ROIs were defined as Table 7.