Pathogenicity, tissue tropism and potential vertical transmission of SARSr-CoV-2 in Malayan pangolins.

Malayan pangolin SARS-CoV-2-related coronavirus (SARSr-CoV-2) is closely related to SARS-CoV-2. However, little is known about its pathogenicity in pangolins. Using CT scans we show that SARSr-CoV-2 positive Malayan pangolins are characterized by bilateral ground-glass opacities in lungs in a similar manner to COVID-19 patients. Histological examination and blood gas tests are indicative of dyspnea. SARSr-CoV-2 infected multiple organs in pangolins, with the lungs the major target, and histological expression data revealed that ACE2 and TMPRSS2 were co-expressed with viral RNA. Transcriptome analysis indicated that virus-positive pangolins were likely to have inadequate interferon responses, with relative greater cytokine and chemokine activity in the lung and spleen. Notably, both viral RNA and viral proteins were detected in three pangolin fetuses, providing initial evidence for vertical virus transmission. In sum, our study outlines the biological framework of SARSr-CoV-2 in pangolins, revealing striking similarities to COVID-19 in humans.

Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases.

Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.

Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus.

AIM: Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram. METHODS: In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model. RESULTS: Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability. CONCLUSION: The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.

Resting-state brain plasticity is associated with the severity in cervical spondylotic myelopathy.

OBJECTIVE: To investigate the brain mechanism of non-correspondence between imaging presentations and clinical symptoms in cervical spondylotic myelopathy (CSM) patients and to test the utility of brain imaging biomarkers for predicting prognosis of CSM. METHODS: Forty patients with CSM (22 mild-moderate CSM, 18 severe CSM) and 25 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. DTI at the spinal cord (level C2/3) with fractional anisotropy (FA) and degree centrality (DC) were recorded. Then one-way analysis of covariance (ANCOVA) was conducted to detect the group differences in the DC and FA values across the three groups. Pearson correlation analysis was then separately performed between JOA with FA and DC. RESULTS: Among them, degree centrality value of left middle temporal gyrus exhibited a progressive increase in CSM groups compared with HCs, the DC value in severe CSM group was higher compared with mild-moderate CSM group. (P < 0.05), and the DC values of the right superior temporal gyrus and precuneus showed a decrease after increase. Among them, DC values in the area of precuneus in severe CSM group were significantly lower than those in mild-moderate CSM and HCs. (P < 0.05). The fractional anisotropy (FA) values of the level C2/3 showed a progressive decrease in different clinical stages, that severe CSM group was the lowest, significantly lower than those in mild-moderate CSM and HCs (P < 0.05). There was negative correlation between DC value of left middle temporal gyrus and JOA scores (P < 0.001), and the FA values of dorsal column in the level C2/3 positively correlated with the JOA scores (P < 0.001). CONCLUSION: Structural and functional changes have taken place in the cervical spinal cord and brain of CSM patients. The Brain reorganization plays an important role in maintaining the symptoms and signs of CSM, aberrant DC values in the left middle temporal gyrus may be the possible mechanism of inconsistency between imaging findings and clinical symptoms. Degree centrality is a potentially useful prognostic functional biomarker in cervical spondylotic myelopathy.

Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

Brain age gap in neuromyelitis optica spectrum disorders and multiple sclerosis.

OBJECTIVE: To evaluate the clinical significance of deep learning-derived brain age prediction in neuromyelitis optica spectrum disorder (NMOSD) relative to relapsing-remitting multiple sclerosis (RRMS). METHODS: This cohort study used data retrospectively collected from 6 tertiary neurological centres in China between 2009 and 2018. In total, 199 patients with NMOSD and 200 patients with RRMS were studied alongside 269 healthy controls. Clinical follow-up was available in 85 patients with NMOSD and 124 patients with RRMS (mean duration NMOSD=5.8±1.9 (1.9-9.9) years, RRMS=5.2±1.7 (1.5-9.2) years). Deep learning was used to learn 'brain age' from MRI scans in the healthy controls and estimate the brain age gap (BAG) in patients. RESULTS: A significantly higher BAG was found in the NMOSD (5.4±8.2 years) and RRMS (13.0±14.7 years) groups compared with healthy controls. A higher baseline disability score and advanced brain volume loss were associated with increased BAG in both patient groups. A longer disease duration was associated with increased BAG in RRMS. BAG significantly predicted Expanded Disability Status Scale worsening in patients with NMOSD and RRMS. CONCLUSIONS: There is a clear BAG in NMOSD, although smaller than in RRMS. The BAG is a clinically relevant MRI marker in NMOSD and RRMS.

The Relationship Between Cortical Morphological and Functional Topological Properties and Clinical Manifestations in Patients with Posttraumatic Diffuse Axonal Injury: An Individual Brain Network Study.

To evaluate the altered network topological properties and their clinical relevance in patients with posttraumatic diffuse axonal injury (DAI). Forty-seven participants were recruited in this study, underwent 3D T1-weighted and resting-state functional MRI, and had single-subject morphological brain networks (MBNs) constructed by Kullback-Leibler divergence and functional brain networks (FBNs) constructed by Pearson correlation measurement interregional similarity. The global and regional properties were analyzed and compared using graph theory and network-based statistics (NBS), and the relationship with clinical manifestations was assessed. Compared with those of the healthy subjects, MBNs of patients with DAI showed a higher path length ([Formula: see text]: P = 0.021, [Formula: see text]: P = 0.011), lower clustering ([Formula: see text]: P = 0.002) and less small-worldness ([Formula: see text]: P = 0.002), but there was no significant difference in the global properties of FBNs (P: 0.161-0.216). For nodal properties of MBNs and FBNs, several regions showed significant differences between patients with DAI and healthy controls (HCs) (P < 0.05, FDR corrected). NBS analysis revealed that MBNs have more altered morphological connections in the frontal parietal control network and interhemispheric connections (P < 0.05). DAI-related global or nodal properties of MBNs were correlated with physical disability or dyscognition (P < 0.05/7, with Bonferroni correction), and the alteration of functional topology properties mediates this relationship. Our results suggested that disrupted morphological topology properties, which are mediated by FBNs and correlated with clinical manifestations of DAI, play a critical role in the short-term and medium-term phases after trauma.

Structural and functional hippocampal alterations in Multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. METHODS: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. RESULTS: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC (p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS (p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS (R = -0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). CONCLUSIONS: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.

Deep learning-based methods may minimize GBCA dosage in brain MRI.

OBJECTIVES: To evaluate the clinical performance of a deep learning (DL)-based method for brain MRI exams with reduced gadolinium-based contrast agent (GBCA) dose to provide better understanding of the readiness and limitations of this method. METHODS: Eighty-three consecutive patients (from March 2019 to August 2019) who underwent brain contrast-enhanced (CE) MRI were included. Three 3D T1-weighted images with zero-dose, low-dose (10%), and full-dose (100%) GBCA were collected. The first 30 cases were used to train a DL model to synthesize the full-dose GBCA images from the zero-dose and low-dose image pairs. The remaining 53 cases were used for testing. The enhancement pattern, number, and location of enhancing lesions were recorded. Overall image quality, image signal noise ratio (SNR), lesion conspicuity, and lesion enhancement were assessed. RESULTS: Lesion detection from the DL-synthesized CE-MRI image accurately matched those from the true full-dose CE-MRI images in 48 of 53 cases (90.6%). The DL method identified the lesions in 34 of 36 cases (94.4%) with a single enhanced lesion and all lesions in 3 of 6 cases (50.0%) in cases with multiple enhancing lesions. The agreement between synthesized and true full-dose CE-MRI images were 0.73, 0.63, 0.89, and 0.87 for image quality, image SNR, lesion conspicuity, and lesion enhancement, respectively. CONCLUSIONS: The proposed DL method is a feasible way to minimize the dosage of GBCAs in brain MRI without sacrificing the diagnostic information. Missing enhancement of small lesions in patients with multiple lesions was observed, requiring improvements in algorithms or dosage design. KEY POINTS: • This study evaluated the clinical performance of a DL-based reconstruction method for significant dose reduction in GBCA contrast-enhanced MRI exams. • The proposed DL method has the potential to satisfy the routine radiological diagnosis needs in certain clinical applications.

Distributed causality in resting-state network connectivity in the acute and remitting phases of RRMS.

BACKGROUND: Although previous studies have shown that intra-network abnormalities in brain functional networks are correlated with clinical/cognitive impairment in multiple sclerosis (MS), there is little information regarding the pattern of causal interactions among cognition-related resting-state networks (RSNs) in different disease stages of relapsing-remitting MS (RRMS) patients. We hypothesized that abnormalities of causal interactions among RSNs occurred in RRMS patients in the acute and remitting phases. METHODS: Seventeen patients in the acute phases of RRMS, 24 patients in the remitting phases of RRMS, and 23 appropriately matched healthy controls participated in this study. First, we used group independent component analysis to extract the time courses of the spatially independent components from all the subjects. Then, the Granger causality analysis was used to investigate the causal relationships among RSNs in the spectral domain and to identify correlations with clinical indices. RESULTS: Compared with the patients in the acute phase of RRMS, patients in the remitting phase of RRMS showed a significantly lower expanded disability status scale, modified fatigue impact scale scores, and significantly higher paced auditory serial addition test (PASAT) scores. Compared with healthy subjects, during the acute phase, RRMS patients had significantly increased driving connectivity from the right executive control network (rECN) to the anterior salience network (aSN), and the causal coefficient was negatively correlated with the PASAT score. During the remitting phase, RRMS patients had significantly increased driving connectivity from the rECN to the aSN and from the rECN to the visuospatial network. CONCLUSIONS: Together with the disease duration (mean disease duration < 5 years) and relatively better clinical scores than those in the acute phase, abnormal connections, such as the information flow from the rECN to the aSN and the rECN to the visuospatial network, might provide adaptive compensation in the remitting phase of RRMS.

Resting cerebral blood flow alterations specific to the comitant exophoria patients revealed by arterial spin labeling perfusion magnetic resonance imaging.

PURPOSE: It has been shown in many previous studies that there were significant changes of the brain anatomy and function in strabismus. However, the significance of the alterations of resting cerebral blood flow (CBF) in comitant exophoria (CE) remains obscure. Arterial spin labeling (ASL) MRI, which is a noninvasive method, could be applied to detect the cerebral blood flow quantitatively. Our study aimed to compare the resting CBF between the comitant exophoria and health controls using pseudo-continuous arterial spin labeling (pCASL) perfusion MRI method. METHODS: 32 patients (25 males and 7 females) with CE (study group), and 32 (25 males and 7 females) healthy individuals with matched age and sex status (control group) underwent a whole-brain pCASL magnetic resonance (MR) examination at the resting state. The resting CBF were voxel-wise compared between the two groups using an analysis of variance designed in a statistical parametric mapping program. The CE patients were distinguishable from the healthy controls (HCs) by receiver operating characteristic (ROC) curves. RESULTS: Compared with the control group, the CE group showed significantly increased resting CBF values in the right parahippocampal regions, bilateral medial frontal gyrus/anterior cingulate cortex, left inferior frontal gyrus, right inferior frontal gyrus, left superior frontal gyrus, bilateral medial cingulate cortex, right middle frontal gyrus, and right paracentral lobule. CONCLUSION: Comitant exophoria showed increased resting CBF in eye movement-related brain areas including supplementary eye field, cingulate eye field and frontal eye field, which could be an explanation of the brain function compensation for the ocular motility disorders in the CE patients.

Detection of Functional Homotopy in Traumatic Axonal Injury.

OBJECTIVE: This study aimed to explore the interhemispheric intrinsic connectivity in traumatic axonal injury (TAI) patients. METHODS: Twenty-one patients with TAI (14 males, seven females; mean age, 38.71 ± 15.25 years) and 22 well-matched healthy controls (16 males, six females; mean age, 38.50 ± 13.82 years) were recruited, and from them we obtained resting-state fMRI data. Interhemispheric coordination was examined using voxel-mirrored homotopic connectivity (VMHC) and seed-based functional connectivity analysis was performed. RESULTS: We observed significantly decreased VMHC in a number of regions in TAI patients, including the prefrontal, temporal, occipital, parietal, and posterior cingulate cortices, thalami and cerebellar posterior lobes. Subsequent seed-based functional connectivity analysis revealed widely disrupted functional connectivity between the regions of local homotopic connectivity deficits and other areas of the brain, particularly the areas subserving the default, salience, integrative, and executive systems. The lower VMHC of the inferior frontal gyrus and basal ganglia, thalamus, and caudate were significant correlated with the Beck Depression Inventory score, Clinical Dementia Rating score, and Mini-Mental State Examination score, respectively. CONCLUSION: TAI is associated with regionally decreased interhemispheric interactions and extensively disrupted seed-based functional connectivity, generating further evidence of diffuse disconnection being associated with clinical symptoms in TAI patients. KEY POINTS: • Traumatic axonal injury is associated with decreased interhemispheric connectivity • Traumatic axonal injury couples with widely disrupted functional connectivity • These alterations support the default, salience, integrative, and executive functions.

Prolonged CT urography in duplex kidney.

BACKGROUND: Duplex kidney is a common anomaly that is frequently associated with multiple complications. Typical computed tomography urography (CTU) includes four phases (unenhanced, arterial, parenchymal and excretory) and has been suggested to considerably aid in the duplex kidney diagnosi. Unfortunately, regarding duplex kidney with prolonged dilatation, the affected parenchyma and tortuous ureters demonstrate a lack of or delayed excretory opacification. We used prolonged-delay CTU, which consists of another prolonged-delay phase (1- to 72-h delay; mean delay: 24 h) to opacify the duplicated ureters and affected parenchyma. METHODS: Seventeen patients (9 males and 8 females; age range: 2.5-56 y; mean age: 40.4 y) with duplex kidney were included in this study. Unenhanced scans did not find typical characteristics of duplex kidney, except for irregular perirenal morphology. Duplex kidney could not be confirmed on typical four-phase CTU, whereas it could be easily diagnosed in axial and CT-3D reconstruction using prolonged CTU (prolonged-delay phase). RESULTS: Between January 2005 and October 2010, in this review board-approved study (with waived informed consent), 17 patients (9 males and 8 females; age range: 2.5 ~ 56 y; mean age: 40.4 y) with suspicious duplex kidney underwent prolonged CTU to opacify the duplicated ureters and confirm the diagnosis. CONCLUSION: Our results suggest the validity of prolonged CTU to aid in the evaluation of the function of the affected parenchyma and in the demonstration of urinary tract malformations.

Decreased Regional Homogeneity in Patients With Acute Mild Traumatic Brain Injury: A Resting-State fMRI Study.

Mild traumatic brain injury (mTBI) is characterized by structural disconnection and large-scale neural network dysfunction in the resting state. However, little is known concerning the intrinsic changes in local spontaneous brain activity in patients with mTBI. The aim of the current study was to assess regional synchronization in acute mTBI patients. Fifteen acute mTBI patients and 15 sex-, age-, and education-matched healthy controls (HCs) were studied. We used the regional homogeneity (ReHo) method to map local connectivity across the whole brain and performed a two-sample t-test between the two groups. Compared with HCs, patients with acute mTBI showed significantly decreased ReHo in the left insula, left precentral/postcentral gyrus, and left supramarginal gyrus (p < 0.05, AlphaSim corrected). The ReHo index of the left insula showed a positive correlation with the Mini-Mental State Examination (MMSE) scores across all acute mTBI patients (p < 0.05, uncorrected). The ReHo method may provide an objective biomarker for evaluating the functional abnormity of mTBI in the acute setting.

The association between glymphatic system dysfunction and alterations in cerebral function and structure in patients with white matter hyperintensities.

The objective of this study is to explore the relationship between the glymphatic system and alterations in the structure and function of the brain in white matter hyperintensity (WMH) patients. MRI data were collected from 27 WMH patients and 23 healthy controls. We calculated the along perivascular space (ALPS) indices, the anterior corner distance of the lateral ventricle, and the width of the third ventricle for each subject. The DPABISurf tool was used to calculate the cortical thickness and cortical area. In addition, data processing assistant for resting-state fMRI was used to calculate regional homogeneity, degree centrality, amplitude low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and voxel-mirrored homotopic connectivity (VMHC). In addition, each WMH patient was evaluated on the Fazekas scale. Finally, the correlation analysis of structural indicators and functional indicators with bilateral ALPS indices was investigated using Spearman correlation analysis. The ALPS indices of WMH patients were lower than those of healthy controls (left: t = -4.949, P < 0.001; right: t = -3.840, P < 0.001). This study found that ALFF, fALFF, regional homogeneity, degree centrality, and VMHC values in some brain regions of WMH patients were alternated (AlphaSim corrected, P < 0.005, cluster size > 26 voxel, rmm value = 5), and the cortical thickness and cortical area of WMH patients showed trend changes (P < 0.01, cluster size > 20 mm2, uncorrected). Interestingly, we found significantly positive correlations between the left ALPS indices and degree centrality values in the superior temporal gyrus (r = 0.494, P = 0.009, P × 5 < 0.05, Bonferroni correction). Our results suggest that glymphatic system impairment is related to the functional centrality of local connections in patients with WMH. This provides a new perspective for understanding the pathological mechanisms of cognitive impairment in the WMH population.

Glymphatic system dysfunction in recovered patients with mild COVID-19: A DTI-ALPS study.

Central nervous sequelae are often reported in recovered patients with COVID-19. It is not clear whether recovered COVID-19 patients have glymphatic impairment and clinical correlation. In this study, we demonstrated that mild COVID-19 patients experienced asymmetric bilateral glymphatic function decline after four months of recovery, and the decrease in glymphatic function was more obvious in older recovered patients. Our results further showed that recovered patients with right-sided glymphatic dysfunction experienced a greater proportion of cognitive decline (MoCA score <26) than patients with left-sided glymphatic dysfunction. With COVID-19 infection over 90% of the general population currently, future studies of cognitive disorders in the older population should consider the impact of COVID-19 infection.

Hypo-connectivity of the primary somatosensory cortex in Parkinson's disease: a resting-state functional MRI study.

Background: Parkinson's disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a "pure" sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson's disease (PD), an area that has received limited attention in previous neuroimaging studies. Methods: This study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients. Results: In the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p < 0.001, corrected using network-based methods). In connectivity maps, hypo-connectivity was primarily observed in the sensorimotor network as common patterns (p < 0.001, corrected for false discovery rate) and in the default mode network (DMN) as distinct patterns. Moreover, this study identified a negative association between the correlation matrix within S1 subregions and the scores for axial symptoms and postural instability/gait difficulty (PIGD) in PD patients. Nevertheless, a direct relationship between the connectivity maps of S1 subregions and clinical assessment scales was not established. Conclusion: This study offers novel insights into the neurobiological mechanisms that contribute to S1 dysfunction in PD, highlighting the significant involvement of S1 hypo-connectivity in the motor disturbances observed in PD patients.