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Abnormal brain regions with altered nodal parameters in brain white matter structural networks in the patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE) and the healthy controls (HC). The red nodes indicate that the nodal efficiency in the non-NPSLE patients was uniformly significantly decreased compared to the controls. The pink nodes indicate no significant between-group differences in the nodal efficiency. The size of the red nodes is proportion to the nodal efficiency value for the non-NPSLE patients. The brain networks, which were visualized using BrainNet Viewer software (http://www.nitrc.org/projects/bnv/), are for illustration purposes only. Abbreviations: PreCG, precentral gyrus; MFG, middle frontal gyrus; IPL, inferior parietal lobe; DCG, median cingulate and paracingulate gyri; and MTG, middle temporal gyrus
Source publication
Previous neuroimaging studies have revealed cognitive dysfunction in patients with systemic lupus erythematosus (SLE) and suggested that it may be related to disrupted brain white matter (WM) connectivity. However, no study has examined the topological properties of brain WM structural networks in SLE patients, especially in patients with non-neuro...
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Citations
... Decreased AD indicates axonal injury, reduced axonal caliber, or less coherent orientation of axons [28]. Our results about AD metrics are different from findings reported by previous DTI studies on SLE [29,30]. For example,. ...
... For example,. Zhao et al. reported non-NPSLE patients had increased AD in bilateral corticospinal tracts and reduced AD in right superior longitudinal fasciculus-temporal terminations [30]. These discrepant results may be explained by the fact that complex cellular components and structures cannot be well described using the DTI model. ...
Background
Diffusion kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) provide more comprehensive and informative perspective on microstructural alterations of cerebral white matter (WM) than single-shell diffusion tensor imaging (DTI), especially in the detection of crossing fiber. However, studies on systemic lupus erythematosus patients without neuropsychiatric symptoms (non-NPSLE patients) using multi-shell diffusion imaging remain scarce.
Methods
Totally 49 non-NPSLE patients and 41 age-, sex-, and education-matched healthy controls underwent multi-shell diffusion magnetic resonance imaging. Totally 10 diffusion metrics based on DKI (fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis and radial kurtosis) and NODDI (neurite density index, orientation dispersion index and volume fraction of the isotropic diffusion compartment) were evaluated. Tract-based spatial statistics (TBSS) and atlas-based region-of-interest (ROI) analyses were performed to determine group differences in brain WM microstructure. The associations of multi-shell diffusion metrics with clinical indicators were determined for further investigation.
Results
TBSS analysis revealed reduced FA, AD and RK and increased ODI in the WM of non-NPSLE patients (P < 0.05, family-wise error corrected), and ODI showed the best discriminative ability. Atlas-based ROI analysis found increased ODI values in anterior thalamic radiation (ATR), inferior frontal-occipital fasciculus (IFOF), forceps major (F_major), forceps minor (F_minor) and uncinate fasciculus (UF) in non-NPSLE patients, and the right ATR showed the best discriminative ability. ODI in the F_major was positively correlated to C3.
Conclusion
This study suggested that DKI and NODDI metrics can complementarily detect WM abnormalities in non-NPSLE patients and revealed ODI as a more sensitive and specific biomarker than DKI, guiding further understanding of the pathophysiological mechanism of normal-appearing WM injury in SLE.
... 9,10 In another study, a topology model that was created showed significantly lowered global and local network efficiency, prolonged feature path length, and reduced strength of connections. 11 Furthermore, DTI indicated that the extent of brain impairment was related to the severity, activity, and course of the disease. 12 In comparison with DTI, diffusional kurtosis imaging (DKI) is a more accurate and noninvasive imaging technology that can accurately detect changes in tissue structure, particularly in non-homogenous tissue. ...
Purpose
The purpose of this study was to observe cerebral microstructure and microcirculation features, as well as changes in white matter (WM) and gray matter (GM) among patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE).
Methods
We compared 36 female patients with non-NPSLE and 20 age- and gender-matched healthy controls (HCs) who underwent 3.0T MRI imaging with diffusion kurtosis imaging (DKI) and 3D pseudo-continuous Arterial Spin Labeling (pCASL). Mean kurtosis (MK), mean kurtosis tensor (MKT), and cerebral blood flow (CBF) values were obtained from 25 brain regions, including WM and GM. We analyzed the correlation between imaging indicators and clinical data.
Results
When compared with HCs, patients with non-NPSLE had reduced MK and MKT values in regional WM, deep GM, and the left frontal lobe cortical GM, and increased CBF in the right parietal lobe WM and right semioval center (SOC). The MK and MKT values were weakly correlated with CBF in some regions, including WM and GM. Complement 3 (C3) and Complement 4 (C4) showed a weak positive correlation with MK and MKT in some regions, including WM and deep GM, while platelet (PLT) was positively correlated with MKT in the left frontal lobe WM; dsDNA antibody was correlated negatively with MK in the right occipital lobe WM; and erythrocyte sedimentation rate (ESR) was correlated negatively with CBF in the left SOC.
Conclusion
Our findings revealed the presence of brain microstructural and microvascular abnormalities in non-NPSLE patients, indicating microstructural damage in the cortical GM, which was less commonly reported. We found DKI and pCASL useful in detecting early brain lesions, and MK was a more sensitive and beneficial indicator.
... The fiber numbers were used as edges for 90 x 90 structural network matrix of individual participant. Because structural network matrix constructed by FA and fiber numbers exhibited similar network topology [6,25], we only analyzed structural network matrix based on fiber numbers in current study. ...
In patients with Parkinson’s disease (PD), cognitive impairment is common and substantially exacerbates disease severity. The objective of this study is to investigate whether cognitive decline affects disease severity and whether structural network disruption contributes to cognitive impairment in PD patients. PD patients (n = 146) receiving structural and functional magnetic resonance imaging from Parkinson’s Progression Markers Initiative (PPMI) database were included. Based on the scores of Symbol Digit Modalities Test (SDMT), patients were classified into lower quartile group (SDMT score rank: 0%∼25%), interquartile group (SDMT score rank: 26%∼75%), and upper quartile group (SDMT score rank: 76%∼100%) according to their SDMT score quartiles to assess how cognitive function shapes disease manifestations and brain network topology. Patients in the lower quartile group exhibited more severe motor symptoms, non-motor symptoms, and striatal dopamine depletion compared to interquartile group and upper quartile group. In addition, they also showed impaired structural network topology both at global and local levels compared to interquartile group and upper quartile group. Furthermore, different nodal network metrics in structural network contributed to cognitive and motor impairment of PD patients. Taken together, PD patients with worse cognitive function exhibited more severe motor and non-motor symptoms and aberrant structural network metrics were associated with both cognitive and motor decline of PD patients.
... Regarding white matter network, we obtained similar profiles of global and nodal network metrics in FN network and EW network. This indicated that FN network and EW network had almost identical network topology, which was in agreement with the results of a previous study (Zhao et al., 2018). Our finding that MAPT rs17649553 T allele was associated with higher small-worldness γ, λ, and σ of white matter network is novel and significant. ...
Currently, over 90 genetic loci have been found to be associated with Parkinson's disease (PD) in genome-wide association studies, nevertheless, the effects of these genetic variants on the clinical features and brain structure of PD patients are largely unknown. This study investigated the effects of microtubule-associated protein tau (MAPT) rs17649553 (C>T), a genetic variant associated with reduced PD risk, on the clinical manifestations and brain networks of PD patients. We found MAPT rs17649553 T allele was associated with better verbal memory in PD patients. In addition, MAPT rs17649553 significantly shaped the topology of gray matter covariance network and white matter network. Both the network metrics in gray matter covariance network and white matter network were correlated with verbal memory, however, the mediation analysis showed that it was the small-world properties in white matter network that mediated the effects of MAPT rs17649553 on verbal memory. These results suggest that MAPT rs17649553 T allele is associated with higher small-world properties in structural network and better verbal memory in PD.
... Furthermore, diffusion magnetic resonance imaging (dMRI) studies have associated the SLF in working memory of neurotypical children (Farah, Tzafrir, & Horowitz-Kraus, 2020;Vestergaard et al., 2011), adolescents (Østby, Tamnes, Fjell, & Walhovd, 2011;Peters et al., 2012) and adults (Metzler-Baddeley et al., 2017). Research examining working memory difficulties in clinical populations, such as schizophrenia (Karlsgodt et al., 2008) and systemic lupus erythematosus (Zhao et al., 2018), also suggest significant association between SLF organization and their poor performance on a working memory task. Together, this research highlights the potential importance of the SLF in neurotypical working memory and provides a target tract to examine in association with working memory difficulties. ...
Introduction: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder with many functional impairments thought to be underpinned by difficulties in executive function domains such as working memory. The superior longitudinal fasciculus (SLF) plays an integral role in the development of working memory in neurotypical children. Neuroimaging research suggests reduced white matter organization of the SLF may contribute to working memory difficulties commonly seen in ADHD. This study aimed to examine the relationship between white matter organization of the SLF and working memory in children with ADHD.
Methods: We examined the association of tract volume and apparent fibre density (AFD) of the SLF with working memory in children with ADHD (n=64) and controls (n=58) aged 9-11years. Children completed a computerized spatial n-back task and underwent diffusion magnetic resonance imaging (dMRI). Constrained spherical deconvolution-based tractography was used to construct the three branches of the SLF bilaterally and examine volume and AFD of the SLF.
Results: Regression analyses revealed children with ADHD exhibited poorer working memory, and lower volume and AFD of the left SLF-II compared to healthy controls. There was also an association between reaction time and variability (RT and RT-V) and the left SLF-II. Further analyses revealed volume of the left SLF-II mediated the relationship between ADHD and working memory performance (RT and RT-V).
Discussion: These findings add to the current body of ADHD literature, revealing the potential role of frontoparietal white matter in working memory difficulties in ADHD.
... Regarding white matter network, we obtained similar profiles of global and nodal network metrics in FN network and EW network. This indicated that FN network and EW network had almost identical network topology, which was in agreement with the results of a previous study (Zhao et al., 2018). Our findings suggested that gray matter covariance network and white matter network exhibited divergent network topology as previously reported (Gong et al., 2012;Nestor et al., 2017). ...
Background: Currently, over 90 genetic loci have been found to be associated with Parkinson's disease (PD) in genome-wide association studies, nevertheless, the effects of these genetic variants on the clinical features and brain structure of PD patients are largely unknown.
Objective: This study investigated the effects of microtubule-associated protein tau (MAPT), rs17649553 (C>T), a genetic variant associated with reduced PD risk, on the functional and structural networks of PD patients.
Methods: Totally 83 PD subjects from Parkinson's Progression Markers Initiative database were included for this study. They all received structural and functional magnetic resonance imaging and whole exome sequencing. The effects of MAPT rs17649553 on brain structural and functional networks were systematically assessed.
Results: MAPT rs17649553 T allele was associated with better verbal memory in PD patients. In addition, MAPT rs17649553 significantly reshaped the topology of gray matter covariance network and white matter network but not that of functional network. Both the network metrics in gray matter covariance network and white matter network were correlated with verbal memory, however, the mediation analysis showed that it was the small-worldness topology in white matter network that mediated the effects of MAPT rs17649553 on verbal memory.
Conclusion: In sum, we proposed that MAPT rs17649553 T allele was associated with superior structural network topology and better verbal memory in PD. Future studies are needed to determine the role of MAPT rs17649553 in PD initiation and progression.
... Since previous studies have analyzed the volumetric measurements of the entire corpus callosum, no data are available in the literature for comparison. Previous studies on DTI have analyzed different brain areas and observed a significant reduction in DTI-based scalar maps in SLE patients with and without neuropsychiatric manifestations and controls [40][41][42][43][44][45][46][47][48][49][50][51][52]. ...
Central nervous system (CNS) involvement in childhood-onset systemic lupus erythematosus (cSLE) occurs in more than 50% of patients. Structural magnetic resonance imaging (MRI) has identified global cerebral atrophy, as well as the involvement of the corpus callosum and hippocampus, which is associated with cognitive impairment. In this cross-sectional study we included 71 cSLE (mean age 24.7 years (SD 4.6) patients and a disease duration of 11.8 years (SD 4.8) and two control groups: (1) 49 adult-onset SLE (aSLE) patients (mean age of 33.2 (SD 3.7) with a similar disease duration and (2) 58 healthy control patients (mean age of 29.9 years (DP 4.1)) of a similar age. All of the individuals were evaluated on the day of the MRI scan (Phillips 3T scanner). We reviewed medical charts to obtain the clinical and immunological features and treatment history of the SLE patients. Segmentation of the corpus callosum was performed through an automated segmentation method. Patients with cSLE had a similar mid-sagittal area of the corpus callosum in comparison to the aSLE patients. When compared to the control groups, cSLE and aSLE had a significant reduction in the mid-sagittal area in the posterior region of the corpus callosum. We observed significantly lower FA values and significantly higher MD, RD, and AD values in the total area of the corpus callosum and in the parcels B, C, D, and E in cSLE patients when compared to the aSLE patients. Low complement, the presence of anticardiolipin antibodies, and cognitive impairment were associated with microstructural changes. In conclusion, we observed greater microstructural changes in the corpus callosum in adults with cSLE when compared to those with aSLE. Longitudinal studies are necessary to follow these changes, however they may explain the worse cognitive function and disability observed in adults with cSLE when compared to aSLE.
... Recently, brain connectivity has been increasingly used to study the pathological mechanisms of brain involvement. For SLE, studies have also found abnormalities in functional connectivity [42] and white matter connectivity [70,71]. SCN studies on SLE cortex are yet unavailable. ...
Background
Non-neuropsychiatric systemic lupus erythematosus (non-NPSLE) has been confirmed to have subtle changes in brain structure before the appearance of obvious neuropsychiatric symptoms. Previous literature mainly focuses on brain structure loss in non-NPSLE; however, the results are heterogeneous, and the impact of structural changes on the topological structure of patients’ brain networks remains to be determined. In this study, we combined neuroimaging and network analysis methods to evaluate the changes in cortical thickness and its structural covariance networks (SCNs) in patients with non-NPSLE.
Methods
We compare the cortical thickness of non-NPSLE patients ( N =108) and healthy controls (HCs, N =88) using both surface-based morphometry (SBM) and regions of interest (ROI) methods, respectively. After that, we analyzed the correlation between the abnormal cortical thickness results found in the ROI method and a series of clinical features. Finally, we constructed the SCNs of two groups using the regional cortical thickness and analyzed the abnormal SCNs of non-NPSLE.
Results
By SBM method, we found that cortical thickness of 34 clusters in the non-NPSLE group was thinner than that in the HC group. ROI method based on Destrieux atlas showed that cortical thickness of 57 regions in the non-NPSLE group was thinner than that in the HC group and related to the course of disease, autoantibodies, the cumulative amount of immunosuppressive agents, and cognitive psychological scale. In the SCN analysis, the cortical thickness SCNs of the non-NPSLE group did not follow the small-world attribute at a few densities, and the global clustering coefficient appeared to increase. The area under the curve analysis showed that there were significant differences between the two groups in clustering coefficient, degree, betweenness, and local efficiency. There are a total of seven hubs for non-NPSLE, and five hubs in HCs, the two groups do not share a common hub distribution.
Conclusion
Extensive and obvious reduction in cortical thickness and abnormal topological organization of SCNs are observed in non-NPSLE patients. The observed abnormalities may not only be the realization of brain damage caused by the disease, but also the contribution of the compensatory changes within the nervous system.
... This might be another piece of evidence of the lupus-mediated inflammation involving the brain, which is in accordance with previously reported literature (7,91). Although most of the lupus patients in the non-ICVD group did not have MRI scans, multiple previous studies have reported that even in SLE patients without neuropsychiatric manifestations, there is increased WMH lesion load (92)(93)(94), which has been demonstrated to be closely associated with cerebral infarcts, aPLs, and high general SLE activity, along with traditional factors such as age and hypertension (92). Moreover, several prospective MRI studies have indicated that a higher load of deep WMH lesions would progress over time and were independently associated with new stroke onset (95, 96). ...
Objectives
Ischemic cerebrovascular disease (ICVD) is one of the most common and severe complications in systemic lupus erythematosus (SLE). We aim to explore the risk factors for ICVD in SLE and to assess their associated clinical characteristics.
Methods
In this study, 44 lupus patients with ICVD (ICVD-SLE) and 80 age- and sex-matched lupus patients without ICVD (non-ICVD-SLE) who were hospitalized in our center between 2014 and 2021 were enrolled. A comprehensive set of clinical and socio-demographic data was recorded. In the ICVD-SLE group, the modified Rankin score (mRS) at 90 days after the occurrence of ICVD, the brain MRI, and arterial ultrasonography findings were collected. Group comparisons were made with continuous variables using an independent t-test or the Mann–Whitney test, and with categorical variables using the chi-square test or Fisher exact test. Multivariate logistic regression analysis was performed to identify the risk factors for ICVD in SLE. Patients with ICVD-SLE were divided into three subgroups according to the gradations of intracranial arterial stenosis (ICAS). The subgroup comparisons were performed by one-way ANOVA test or Kruskal–Wallis test.
Results
Of the 44 patients with ICVD, 45% had a large-vessel ischemic stroke, 50% had a symptomatic lacunar stroke, and 9% had a transient ischemic attack. 2 (4.5%) had both large-vessel ischemic stroke and symptomatic lacunar stroke. Multivariate logistic regression analysis showed that cutaneous vasculitis (OR=7.36, 95% CI=2.11–25.65), anticardiolipin antibody (aCL) (OR=4.38, 95% CI=1.435–13.350), and lupus anticoagulant (LA) (OR=7.543,95% CI=1.789–31.808) were the risk factors, and hydroxychloroquine (HCQ) therapy (OR=0.198, 95% CI=0.078–0.502) was the protective factor, after controlling for confounders. During the analysis of the subgroups, no significant difference was observed between the patients in the group without internal carotid arterial occlusion (ICAS) and those with severe ICAS except for diagnostic delay. However, patients in the moderate ICAS group were older when SLE occurred (P<0.01), had a longer diagnostic delay (P<0.01), a lower percentage of hypocomplementemia (P=0.05) and steroids and HCQ therapy (P=0.01, P=0.05, respectively), a trend toward lower mRS score, but a higher incidence of carotid atherosclerotic plaque (P<0.01), when compared with the other two subgroups.
Conclusion
Cutaneous vasculitis and antiphospholipid antibodies (aPLs) are associated with an increased risk of ICVD, while HCQ therapy may provide protection against ICVD in SLE. The ICVD in younger lupus patients is associated with complement-mediated inflammation and poorer outcome, and require immunosuppressive therapy, whereas the ICVD in elderly patients are characterized by moderate ICAS and carotid atherosclerotic plaques.
... In recent years, brain connectivity has been widely used to study the pathological mechanism of brain damage. For SLE, studies have also found abnormalities in functional connectivity [42] and white matter connectivity [70,71]. SCNs studies on SLE cortex are yet unavailable. ...
Background
Non-neuropsychiatric systemic lupus erythematosus (non-NPSLE) has been confirmed to have subtle changes in brain structure before the appearance of obvious neuropsychiatric symptoms. Previous literature mainly focuses on brain structure loss in non-NPSLE; however, the results are heterogeneous, and the impact of structural changes on the topological structure of patients' brain network remains to be determined. In this study, we combined neuroimaging and network analysis methods to evaluate the changes in cortical thickness and its structural covariance networks (SCNs) in patients with non-NPSLE.
Methods
We compare the cortical thickness of non-NPSLE patients (N = 108) and healthy controls (HCs, N = 88) using both surface-based morphometry (SBM) and regions of interest (ROIs) method, respectively. After that, we analyzed the correlation between the abnormal cortical thickness results found in the ROIs method and a series of clinical features. Finally, we constructed the SCNs of two groups using the regional cortical thickness, and analyzed the abnormal SCNs of non-NPSLE.
Results
By SBM method, we found that cortical thickness of 34 clusters in the non-NPSLE group was thinner than that in the HCs group. ROIs method based on Destrieux altas showed that cortical thickness of 57 regions in the non-NPSLE group was thinner than that in the HCs group and related to the course of disease, autoantibodies, the cumulative amount of immunosuppressive agents, and cognitive psychological scale. In the SCNs analysis, the cortical thickness SCNs of the non-NPSLE group did not follow the small-world attribute at a few densities, and the global clustering coefficient appeared to increase. The area under the curve analysis showed that there were significant differences between the two groups in clustering coefficient, degree, betweenness, and local efficiency. There are a total of seven hubs for non-NPSLE, and five hubs in HCs, the two groups do not share a common hub distribution.
Conclusion
Extensive and obvious reduction in cortical thickness and abnormal topological organization of SCNs are observed in non-NPSLE patients. The observed abnormalities may not only be the realization of brain damage caused by the disease, but also the contribution of the compensatory changes within the nervous system.
