Acute mountain sickness (AMS) is a natural consequence of hypobaric hypoxia caused by acute exposure to hypoxic high altitude environment, and its exact pathological causes is still under debate ^[1]. Furthermore, hypobaric hypoxia is a concomitant factor with several diseases such as epilepsy and stroke. Hence studying of the anatomical and functional cerebral changes under this process is of great clinical interest ^{[2, 3]}. Changes in gray matter volume were frequently observed in the frontal gyrus, basal ganglia, thalamus, anterior cingulate cortex, and hippocampus, giving rise to the concept of the pain matrix ^[4], whereas headache is the most important symptom in AMS. In this work, we report the changes of gray matter regions at different time points in a longitudinal study where the participants experienced significant changes of altitude. Ten healthy volunteers (males/females: 5/5, age range 24-29) were involved for this study, consent forms were obtained. Volunteers were transported from Beijing (40m) to Lhasa (>3500m) and back during this experiment. The Lake Louise AMS Self-Report Score (LLSelf) was recorded during the time course to assess the severity of acute AMS as a consequence of hypobaric hypoxia. All scans were performed on the MR Discovery 750 (GE Healthcare, MI) scanner equipped with an 8-channel head coil (in vivo, FL). Anatomical brain images were acquired by using a 3D-FSPGR sequence with the following parameters: TR/TE= 6.9/2.9 ms; FOV= 256×256 mm²; matrix= 256×256; slice thickness= 1.0 mm, no gap; 188 slices, with an isotropic 1mm resolution. MR scans were performed on three time points: at sea level prior to departure, during stay at high altitude, back to sea level. and analyzed with VBM8 toolbox (http://dbm.neuro.uni-jena.de/vbm8/) in SPM8 (http://www.fil.ion.ucl.ac.uk/spm) running with Matlab (MathWorks Inc., Natick, MA, USA). Firstly, the raw data in DICOM format were imported into SPM. For brain registrations, T1 weighted images of different volunteers were spatially normalized to Montreal Neurological Institute (MNI) space. Next, T1 weighted image were segmented into gray matter, white matter, and cerebrospinal fluid images by a unified tissue-segmentation procedure after image-intensity non-uniformity correction in SPM8. Subsequently, these segmented gray and white matter images were modulated then reflected the actual brain tissues volume. In order to get the cortical volumes, the regional changes in the absolute amount of GM should be conserved by using Jacobian determinants to modulate the image intensity of each voxel. Finally, modulated GM, WM images in MNI space were smoothed using an 8 mm Gaussian kernel to improve the SNR. To study the changes of gray matter volume with developing of ASM in different stages during experiment, statistical analyses were performed using SPM (Mode specification, review and estimate, Specify 2nd-level, t-test) for data collected at different time points.Results of VBM revealed an increase of gray matter (GM) volume in the posterior lobe of the cerebellum on 3658 m high altitude, as well as a decrease of GM volume in the Left and Right Cerebrum, Temporal Lobe, Inferior Temporal Gyrus, Frontal Lobe, and Frontal Gyrus when compared to the measurements at sea level prior to departure (Fig1-a). At the same time, Thalamus, Cerebellum Posterior Lobe, and Precentral Gyrus showed significantly increased GM volume, while Left or Right Cerebrum, Frontal Lobe and Middle Frontal Gyrus showed significantly decreased volume when subjects returned from high altitude compared to the results on high altitude (Fig1-b). Additionally, no areas with decreased regional GM volumes were observed after returning to sea level compared with those of prior to departure, but Fusiform (left), Hippocampus (left) and Middle temporal gyrus (left) showed significantly increased GM volume (Fig1-c). On the whole, the imaging results before and after high altitude showed similar change pattern contrasts with the results of high altitude. The similar significant regions include some part of left of right Cerebrum, Orbital Gyrus, Temporal Lobe, Middle and Inferior Temporal Gyrus, which revealed the changes of gray matter were associated with ASM development(Fig2).To our knowledge, this is the first experiment conducted with the same subject same scanner at different altitudes to study the cerebral changes attributed to hypobaric hypoxia. It was found that different gray matter regions varied differently in terms of volume changes at different stages of this experiment: several gray matter regions swelled whereas some others shrunk. Detailed study of the volume change and connecting its functional role may lead to better understanding of the global cerebral changes due to hypobaric hypoxia at high altitude, which may convey clinical significance for other diseases.