Guangyao Wu

Progressive atrophy in the optic pathway and visual cortex of early blind Chinese adults: A voxel-based morphometry magnetic resonance imaging study

Many previous neuroimaging studies have shown that the early visual cortex of the early blind (EB) exhibits significant functional plasticity. However, only few previous studies have addressed the question whether or not such functional plasticity is accompanied by, and even related to, structural plasticity. In this study, we acquired high-resolution whole-brain anatomical magnetic resonance images form 14 Chinese EB adults, who lost sight before 6 years of age, and 16 age/gender-matched normal-sighted controls (SC), and compared pixel-by-pixel the gray matter (GM) and white matter (WM) volumes between the two groups with voxel-based morphometry. The results showed that, relative to the SC, the EB exhibits significantly reduced WM volumes in the optic tract and optic radiation and significant GM losses in the early visual cortex. The reduction of WM volume in the optic radiation of the EB was found be modulated by both the age at blindness onset and the duration of blindness. The reduction of GM volume in the early visual cortex of the EB appeared to be unaffected by the age at blindness onset. However, it was found in localized regions of the atrophic early visual cortex of the EB that the GM loss was progressive with aging and increasing duration of blindness. These results suggest that early visual deprivation induces significant structural plasticity in the optic pathway and early visual cortex of the EB, which likely occurs during both the critical period of early neurodevelopment and the course of persisted blindness later in life through activity-dependent mechanisms.

Abnormal frontal cortex white matter connections in bipolar disorder: a DTI tractography study.

OBJECTIVEnIn bipolar disorder, white matter abnormalities have been reported with region-of-interest and voxel-based methods; however, deficits in specific white matter tracts cannot be localized by these methods. Therefore, in this study, we aimed to investigate the white matter tracts that mediate connectivity of the frontal cortex using diffusion tensor imaging (DTI) tractography.nnnMETHODSnEighteen patients with bipolar disorder and sixteen age- and gender-matched healthy subjects underwent DTI examinations. Frontal cortex white matter tracts, including the anterior thalamic radiation (ATR), uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), cingulum, and inferior fronto-occipital fasciculus (IFO) were reconstructed by DTI tractography, and we calculated the mean fractional anisotropy (FA) for each fiber tract. The values were compared between groups by repeated measures analysis of variance with age and gender as covariates, which allowed us to investigate significant differences between the tracts.nnnRESULTSnWhen compared with healthy controls, the patients with bipolar disorder showed significantly decreased FA in the ATR and UF, and a trend towards lower FA in the SLF and cingulum. However, there were no FA differences between groups in the IFO.nnnCONCLUSIONSnOur study indicates that bipolar patients show abnormalities within white matter tracts connecting the frontal cortex with the temporal and parietal cortices and the fronto-subcortical circuits. These findings suggest that alterations in the connectivity of white matter tracts in the frontal cortex might contribute to the neuropathology of bipolar disorder.

Heavy smokers show abnormal microstructural integrity in the anterior corpus callosum: A diffusion tensor imaging study with tract-based spatial statistics

BACKGROUNDnAbnormal macrostructural brain abnormalities in both gray matter and white matter have been reported in cigarette smokers. However, less is known about white matter microstructure in heavy cigarette smokers. In this study, we used diffusion tensor imaging (DTI) to investigate the integrity of the white matter microstructure in heavy smokers.nnnMETHODSnThirty-four heavy smokers and 34 non-smokers participated in this study. Whole brain analysis of fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS) to detect abnormal white matter regions between groups. Volume-of-interest (VOI) analysis was used to investigate changes in diffusivity indices in the regions showing FA abnormalities. Multiple regression analysis was applied to assess the relationships between diffusion indices and smoking-related variables in heavy smokers.nnnRESULTSnCompared with non-smokers, heavy smokers had lower FA in the left anterior (i.e., the genu and rostral body) corpus callosum while exhibiting no areas of higher FA. In the affected region, FA reduction was accompanied by a significantly decreased axial diffusivity and increased radial diffusivity, which suggests that axonal damage and disrupted myelin integrity may be associated with the degraded white matter integrity in heavy smokers. Moreover, significant positive correlations were found between both radial diffusivity and mean diffusivity and the duration of regular smoking.nnnCONCLUSIONSnOur findings suggest that heavy smokers demonstrate abnormal integrity of the white matter microstructure in the anterior corpus callosum, which is related to the duration of regular smoking. In addition, our study may increase the understanding of the neurobiological basis of chronic cigarette smoking.

Altered brain functional networks in heavy smokers

Recent neuroimaging studies have demonstrated that cigarette smoking is associated with changed brain structure and function. However, little is known about alterations of the topological organization of brain functional networks in heavy smokers. Thirty‐one heavy smokers and 33 non‐smokers underwent a resting‐state functional magnetic resonance imaging scan. The whole‐brain functional networks were constructed by thresholding the correlation matrices of 90 brain regions and their topological properties were analyzed using graph network analysis. Non‐parametric permutation tests were performed to investigate group differences in network topological measures and multiple regression analysis was conducted to determine the relationships between the network metrics and smoking‐related variables. Both heavy smokers and non‐smokers exhibited small‐world architecture in their brain functional networks. Compared with non‐smokers, however, heavy smokers showed altered topological measurements characterized by lower global efficiency, higher local efficiency and clustering coefficients and greater path length. Furthermore, heavy smokers demonstrated decreased nodal global efficiency mainly in brain regions within the default mode network, whereas increased nodal local efficiency predominated in the visual‐related regions. In addition, heavy smokers exhibited an association between the altered network metrics and the duration of cigarette use or the severity of nicotine dependence. Our results suggest that heavy smokers may have less efficient network architecture in the brain, and chronic cigarette smoking is associated with disruptions in the topological organization of brain networks. Our findings may further the understanding of the effects of chronic cigarette smoking on the brain and the pathophysiological mechanisms underlying nicotine dependence.

Detection of the mild emphysema by quantification of lung respiratory airways with hyperpolarized xenon diffusion MRI.

To demonstrate the feasibility to quantify the lung respiratory airway in vivo with hyperpolarized xenon diffusion magnetic resonance imaging (MRI), which is able to detect mild emphysema in the rat model.

Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI.

White Matter Development is Potentially Influenced in Adolescents with Vertically Transmitted HIV Infections: A Tract-Based Spatial Statistics Study

BACKGROUND AND PURPOSE: Convergent evidence indicates that HIV is associated with abnormal WM microstructure in adults. However, little is known about whether HIV affects WM development in adolescents. In this study, we used DTI to investigate the integrity of WM microstructure in adolescents with vertically transmitted HIV infections. MATERIALS AND METHODS: Fifteen HIV-positive adolescents with vertically transmitted infections and 26 HIV-negative controls participated in this study. Whole-brain analysis of fractional anisotropy was performed by Tract-Based Spatial Statistics to localize abnormal WM regions between groups. VOI analysis was further performed to explore the changes in diffusivity indices in the regions with fractional anisotropy alterations. Correlation analyses were used to assess the relationship between fractional anisotropy alterations and clinical measures within the HIV-positive group. RESULTS: Relative to HIV-negative controls, HIV-positive adolescents demonstrated significantly reduced fractional anisotropy in the corpus callosum, superior and posterior corona radiata, frontal and parietal WM, pre-/postcentral gyrus, and superior longitudinal fasciculus. In the affected regions, fractional anisotropy reductions were caused by an increase in radial diffusivity, and no changes were observed in axial diffusivity. Moreover, fractional anisotropy values in the bilateral frontal WM were negatively correlated with the duration of highly active antiretroviral therapy and were positively associated with the age at onset of highly active antiretroviral therapy. CONCLUSIONS: These findings suggest that early HIV infections may affect WM development, especially in the frontal WM, corpus callosum, and corona radiata in adolescents, which may be associated with hypomyelination and demyelination. Moreover, WM integrity may serve as a potential new treatment target.

Overexpression of miR‑185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease

Parkinsons disease (PD) is an age-associated neurodegenerative disorder characterized by the death of dopaminergic neurons in the substantia nigra pars compacta. Activation of 5′-adenosine monophosphate-activated protein kinase (AMPK) has been suggested to be associated with PD pathogenesis. The aim of the present study was to investigate the effects of the aberrant expression of microRNA-185 (miR-185) in PD. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced in vitro model of PD was generated using the human SH-SY5Y dopaminergic neuroblastoma cell line, in order to examine the potential molecular mechanisms underlying the roles of miR-185 in PD. miR-185 expression was assessed in MPTP-treated SH-SY5Y cells using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, MPTP-treated SH-SY5Y cells were transfected with a miR-185 mimic or scramble miRNA, and flow cytometry was used to evaluate the level of cellular apoptosis. The expression of autophagy markers, including Beclin 1, microtubule-associated protein light chain 3 (LC3) I and LC3II, as well as key molecules involved in the AMPK/mechanistic target of rapamycin (mTOR) signaling pathway, such as phosphorylated (p)-AMPK and p-mTOR, was examined using RT-qPCR and western blot analyses. In addition, SH-SY5Y cells were treated with the AMPK inhibitor, Compound C, and its effects on cellular apoptosis were assessed. The results demonstrated that miR-185 was significantly downregulated in SH-SY5Y cells treated with MPTP at concentrations of >100 µM when compared with untreated controls. Following transfection with a miR-185 mimic, miR-185 expression in SH-SY5Y cells was significantly increased when compared with blank control cells. Notably, miR-185 overexpression was revealed to significantly reduce the MPTP-induced increase in cellular apoptosis. In addition, the expression levels of Beclin 1, LC3I/II, p-AMPK and p-mTOR were significantly upregulated in MPTP-treated SH-SY5Y cells; whereas miR-185 overexpression significantly downregulated the expression of these factors. Furthermore, miR-185 overexpression significantly suppressed apoptosis of SH-SY5Y cells treated with MPTP plus Compound C when compared with the Compound C group. In conclusion, the results of the present study suggest that overexpression of miR-185 may inhibit autophagy and apoptosis of dopaminergic cells in PD potentially via regulation of the AMPK/mTOR signaling pathway. Therefore, AMPK/mTOR-mediated autophagy and apoptotic signaling pathways may be potential novel therapeutic targets for the development of alternative strategies for the treatment of patients with PD.

Altered Activation in Cerebellum Contralateral to Unilateral Thalamotomy May Mediate Tremor Suppression in Parkinson’s Disease: A Short-Term Regional Homogeneity fMRI Study

Background Ventral intermediate nucleus thalamotomy is an effective treatment for Parkinson’s disease tremor. However, its mechanism is still unclear. Purpose We used resting-state fMRI to investigate short-term ReHo changes after unilateral thalamotomy in tremor-dominant PD, and to speculate about its possible mechanism on tremor suppression. Methods 26 patients and 31 healthy subjects (HS) were recruited. Patients were divided into two groups according to right- (rPD) and left-side (lPD) thalamotomy. Tremor was assessed using the 7-item scale from the Unified Parkinson’s disease rating scale motor score (mUPDRS). Patients were scanned using resting state fMRI after 12h withdrawal of medication, both preoperatively (PDpre) and 7- day postoperatively (PDpost), whereas healthy subjects were scanned once. The regions associated with tremor and altered ReHo due to thalamic ablation were examined. Results The impact of unilateral VIM thalamotomy was characterized in the frontal, parietal, temporal regions, basal ganglia, thalamus, and cerebellum. Compared with PDpre, significantly reduced ReHo was found in the left cerebellum in patients with rPDpost, and slightly decreased ReHo in the cerebellum vermis in patients with lPDpost, which was significantly higher than HS. We demonstrated a positive correlation between the ReHo values in the cerebellum (in rPD, peak coordinate [-12, -54, -21], R = 0.64, P = 0.0025, and peak coordinate [-9, -54, -18], R = 0.71, P = 0.0025; in lPD, peak coordinate [3, -45, -15], R = 0.71, P = 0.004) in the pre-surgical condition, changes of ReHo induced by thalamotomy (in rPD, R = 0.63, P = 0.021, R = 0.6, P = 0.009; in lPD, R = 0.58, P = 0.028) and tremor scores contralateral to the surgical side, respectively. Conclusion The specific area that may be associated with PD tremor and altered ReHo due to thalamic ablation is the cerebellum. The neural basis underlying thalamotomy is complex; cerebellum involvement is far beyond cerebello-thalamic tract breakage.

Structural Covariance of Gray Matter Volume in HIV Vertically Infected Adolescents.

Human immunodeficiency virus (HIV) infection significantly affect neurodevelopmental and behavioral outcomes. We investigated whether alterations of gray matter organization and structural covariance networks with vertical HIV infection adolescents exist, by using the GAT toolbox. MRI data were analysed from 25 HIV vertically infected adolescents and 33 HIV-exposed-uninfected control participants. The gray matter volume (GMV) was calculated, and structural brain networks were reconstructed from gray matter co-variance. Gray matter losses were pronounced in anterior cingulate cortex (ACC), right pallidum, right occipital lobe, inferior parietal lobe, and bilateral cerebellum crus. The global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in frontal, temporal, basal ganglia, cerebellum, and temporal lobes. Brain hubs in the HIV-infected subjects increased in number and tended to shift to sensorimotor and temporal areas. In the HIV-infected subjects, decreased GMVs in ACC and bilateral cerebellum were related to lower Mini-Mental State Examination scores; the CD4 counts were positively related to the GMVs in ACC and sensorimotor areas. These findings suggest that focally reduced gray matter, disrupted nodal profiles of structural wirings, and a shift in hub distribution may represent neuroanatomical biomarkers of HIV infection on the developing brain.