Jiaxing Zhang

Prolonged high-altitude residence impacts verbal working memory: an fMRI study

Oxygen is critical to normal brain functioning and development. In high altitude where the oxygen concentration and pressure are very low, human cognitive capability such as working memory has been found to be jeopardized. Such effect might persist with long-term high-altitude residence. The current study investigated the verbal working memory of 28 high-altitude residents with blood level oxygen dependent (BOLD) functional magnetic resonance imaging (fMRI), in contrast with that of the 30 sea level residents. All of the subjects were healthy college students, matched on their age, gender ratio and social-economic status; they also did not show any difference on their hemoglobin level. The high-altitude subjects showed longer reaction time and decreased response accuracy in behavioral performance. Both groups showed activation in the typical regions associated with the 2-back verbal working memory task, and the behavioral performance of both groups showed significant correlations with the BOLD signal change amplitude and Granger causality values (as a measure of the interregional effective connectivity) between these regions. With group comparison statistics, the high-altitude subjects showed decreased activation at the inferior and middle frontal gyrus, the middle occipital and the lingual gyrus, the pyramis of vermis, as well as the thalamus. In conclusion, the current study revealed impairment in verbal working memory among high-altitude residents, which might be associated with the impact of prolonged chronic hypoxia exposure on the brain functionality.

Adaptive Influence of Long Term High Altitude Residence on Spatial Working Memory: An fMRI Study.

With an increasing population living at a high altitude (HA), the impact of HA residence on human cognitive function has raised concerns. We recruited two groups of college students with one group born and grew up at HA until early adulthood and the control group born and grew up at near sea level (SL); the two groups were matched at age, gender ratio, educational level, the ancestral lines, and peripheral physiology (especially the hemoglobin concentration). A 2-back spatial working memory task was performed by each subject in the scanner while fMRI data were acquired. Compared to the SL control group, the HA group showed equal response accuracy, with more variance in reaction time and a larger average value. fMRI data indicated that both groups showed common activation patterns in the neural pathway typically associated with working memory. The HA group had greater activation at the left pyramis, the left superior temporal gyrus and less activation at the left middle occipital gyrus. Significant correlations were found within each group between the reaction times and BOLD signal change amplitudes at the frontal cortex and the precentral cortex.

Structural Modifications of the Brain in Acclimatization to High-Altitude

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.

Cerebral and functional adaptation with chronic hypoxia exposure: A multi-modal MRI study

The current study obtained multi-modal MRI data from 28 immigrant high altitude (HA) young adults who were born and grew up at Qinghai-Tibetan plateau matched with 28 matched sea level (SL) controls. We compared their regional gray matter volumes (VBM) and white matter quality (DAI FA values) as well as resting state brain activity (Regional Homogeneity (ReHo) of BOLD-fMRI). We found that HA residents showed decreased gray matter volume at bilateral anterior insula, bilateral prefrontal cortex, the left precentral, the left cingulate and the right lingual cortex; accompanied by changed FA and ReHo values in relevant and other regions. The resting state activity at the hippocampus and the right insula were increasing with SL relocation. The HA subjects performed worse on a series of working memory tasks, with the ReHo values of several regions as significant predictors of their performance. This study demonstrated the cerebral and functional modifications with chronic high altitude hypoxia.

Grey and white matter abnormalities in chronic obstructive pulmonary disease: a case–control study

Objectives The irreversible airflow limitation characterised by chronic obstructive pulmonary disease (COPD) causes a decrease in the oxygen supply to the brain. The aim of the present study was to investigate brain structural damage in COPD. Design Retrospective case–control study. Patients with COPD and healthy volunteers were recruited. The two groups were matched in age, gender and educational background. Setting A hospital and a number of communities: they are all located in southern Fujian province, China. Participants 25 stable patients and 25 controls were enrolled from December 2009 to May 2011. Methods Using voxel-based morphometry and tract-based spatial statistics based on MRI to analyse grey matter (GM) density and white matter fractional anisotropy (FA), respectively, and a battery of neuropsychological tests were performed. Results Patients with COPD (vs controls) showed decreased GM density in the limbic and paralimbic structures, including right gyrus rectus, left precentral gyrus, bilateral anterior and middle cingulate gyri, bilateral superior temporal gyri, bilateral anterior insula extending to Rolandic operculum, bilateral thalamus/pulvinars and left caudate nucleus. Patients with COPD (vs controls) had decreased FA values in the bilateral superior corona radiata, bilateral superior and inferior longitudinal fasciculus, bilateral optic radiation, bilateral lingual gyri, left parahippocampal gyrus and fornix. Lower FA values in these regions were associated with increased radial diffusivity and no changes of longitudinal diffusivity. Patients with COPD had poor performances in the Mini-Mental State Examination, figure memory and visual reproduction. GM density in some decreased regions in COPD had positive correlations with arterial blood Po2, negative correlations with disease duration and also positive correlations with visual tasks. Conclusion The authors demonstrated that COPD exhibited loss of regional GM accompanied by impairment of white matter microstructural integrity, which was associated with disease severity and may underlie the pathophysiological and psychological changes of COPD.

Reduced Regional Gray Matter Volume in Patients with Chronic Obstructive Pulmonary Disease: A Voxel-Based Morphometry Study

BACKGROUND AND PURPOSE: Decreased oxygen supply may cause neuronal damage in the brains of patients with COPD, which is manifested by clinical symptoms such as neuropsychological deficits and mood disorders. The aim of the present study was to investigate brain gray matter change in COPD. MATERIALS AND METHODS: Using voxel-based morphometry based on the high-resolution 3D T1-weighted MR images of GM volume, we investigated 25 stable patients with COPD and 25 matching healthy volunteers. A battery of neuropsychological tests was also performed. RESULTS: Patients with COPD (versus controls) showed reduced GM volume in the frontal cortex (bilateral gyrus rectus, bilateral orbital and inferior triangular gyri, and left medial superior gyrus), right anterior insula, cingulate cortex (left anterior and middle gyri, right middle gyrus), right thalamus/pulvinar, right caudate, right putamen, right parahippocampus, and left amygdala. In COPD, in some of these regions, regional GM volume had positive correlations with arterial blood po2, while in some regions, regional GM volume had negative correlations with disease duration. Patients with COPD (versus controls) had poorer performance in the Mini-Mental State Examination, Visual Reproduction, and Figure Memory tests. Moreover, the GM volume in the inferior triangular frontal cortex in patients with COPD was significantly correlated with the Picture Memory score. CONCLUSIONS: Our findings suggest GM reductions in a number of brain regions in COPD, which were associated with disease severity and may underlie the pathophysiologic and psychological changes in patients with COPD.

Minimal Effects on Human Memory Following Long-Term Living at Moderate Altitude

A number of studies describe memory deficits at extremely high altitudes. However, little is known about the effect of long-term living at moderate altitude (MA). The subjects for this study were 52 college students originally from sea level (SL), but studying at a MA of 2260 m over a 7-month period, with a return to SL for 30 days in the middle of the period. Fifty-two matched college students who stayed at SL all the time were the control group. The neuropsychological battery of assessments included the Chinese revised version of Wechsler Memory Scale tests (WMS-CR), verbal and spatial two-back working memory tests, long-term explicit memory (word recall and recognition of words, faces, and pictures) tests, Rey Auditory Verbal Learning test, Rey-Osterrieth Complex Figure (ROCF) test, degraded picture naming test, and the Serial Reaction Time Test. We found that the MA subjects showed significantly poorer performances than SL controls only in short-term visual construction assessed in the visual reproduction test from WMS-CR and in the ROCF immediate test. There were no significant differences in all other tasks between the MA group and SL group. These findings suggest that long-term hypoxic exposure at moderate altitude has minimal effects on human memory.

Cerebrovascular reactivity among native-raised high altitude residents: an fMRI study

BackgroundThe impact of long term residence on high altitude (HA) on human brain has raised concern among researchers in recent years. This study investigated the cerebrovascular reactivity among native-born high altitude (HA) residents as compared to native sea level (SL) residents. The two groups were matched on the ancestral line, ages, gender ratios, and education levels. A visual cue guided maximum inspiration task with brief breath holding was performed by all the subjects while Blood-Oxygenation-Level-Dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) data were acquired from them.ResultsCompared to SL controls, the HA group showed generally decreased cerebrovascular reactivity and longer delay in hemodynamic response. Clusters showing significant differences in the former aspect were located at the bilateral primary motor cortex, the right somatosensory association cortex, the right thalamus and the right caudate, the bilateral precuneus, the right cingulate gyrus and the right posterior cingulate cortex, as well as the left fusiform gyrus and the right lingual cortex; clusters showing significant differences in the latter aspect were located at the precuneus, the insula, the superior frontal and temporal gyrus, the somatosensory cortex (the postcentral gyrus) and the cerebellar tonsil. Inspiratory reserve volume (IRV), which is an important aspect of pulmonary function, demonstrated significant correlation with the amount of BOLD signal change in multiple brain regions, particularly at the bilateral insula among the HA group.ConclusionsNative-born HA residents generally showed reduced cerebrovascular reactivity as demonstrated in the hemodynamic response during a visual cue guided maximum inspiration task conducted with BOLD-fMRI. This effect was particularly manifested among brain regions that are typically involved in cerebral modulation of respiration.

Reduced cortical thickness, surface area in patients with chronic obstructive pulmonary disease: a surface-based morphometry and neuropsychological study

Neural impairments accompanying chronic obstructive pulmonary disease (COPD) have received growing research attention. Previous neuroimaging studies exclusively used volumetric methods to measure cortical volume as a whole rather than focusing on anatomical and neuropathological distinct indices. Here we decomposed the cortical architecture into cortical thickness (CTh), surface area (SA), and gyrification, for the first time, to provide a more integrative profile of brain damage in COPD. Clinical T1-weighted MRI scans were acquired in 25 stable COPD patients (mean age 69) and 25 age-matched controls. Images were processed using surface-based morphometry to obtain cortical parameters enabling more accurate measurement in deep sulci and localized regional mapping. Demographic, physiological, and cognitive assessments were made and correlated with cortical indices. Compared to controls, COPD patients showed significantly reduced CTh broadly distributed in motor, parietal, and prefrontal cortices, together with more circumscribed SA reduction in dorsomedial prefrontal cortex and Broca’s area (cluster-level P < 0.05 corrected). No abnormal gyrification was detected. Decreased CTh in parietofrontal networks strongly correlated with visuospatial construction impairment in COPD patients. Furthermore, thinner dorsolateral prefrontal cortex (DLPFC) best predicted poorer performance (r2 = 0.315, P = 0.004), and was associated with lower arterial oxygen saturation. These data indicate that cortical thinning is a key morphologic feature associated with COPD that could be partly attributed to oxygen desaturation and contributes to COPD visual memory and drawing deficits. Surface-based morphometry provides valuable information concerning COPD, and could ultimately help us to characterize the neurodegenerative pattern and to clarify neurologic mechanisms underlying cognitive dysfunction in COPD patients.

Structural modulation of brain development by oxygen: evidence on adolescents migrating from high altitude to sea level environment.

The present study aimed to investigate structural modulation of brain by high level of oxygen during its peak period of development. Voxel-based morphometry analysis of gray matter (GM) and white matter (WM) volumes and Tract-Based Spatial Statistics analysis of WM fractional anisotropy (FA) and mean diffusion (MD) based on MRI images were carried out on 21 Tibetan adolencents (15–18 years), who were born and raised in Qinghai-Tibetan Plateau (2900–4700 m) and have lived at sea level (SL) in the last 4 years. The control group consisted of matched Tibetan adolescents born and raised at high altitude all the time. SL immigrants had increased GM volume in the left insula, left inferior parietal gyrus, and right superior parietal gyrus and decreased GM in the left precentral cortex and multiple sites in cerebellar cortex (left lobule 8, bilateral lobule 6 and crus 1/2). Decreased WM volume was found in the right superior frontal gyrus in SL immigrants. SL immigrants had higher FA and lower MD at multiple sites of WM tracts. Moreover, we detected changes in ventilation and circulation. GM volume in cerebellum lobule 8 positively correlated with diastolic pressure, while GM volume in insula positively correlated vital capacity and hypoxic ventilatory response. Our finding indicate that the structural modulations of GM by high level of oxygen during its peak period of development are related to respiratory and circulatory regulations, while the modulation in WM mainly exhibits an enhancement in myelin maturation.