Altered volume of the amygdala subregions in patients with chronic low back pain.

Background: Neuroimaging studies have suggested a pivotal role for the amygdala involvement in chronic low back pain (CLBP). However, the relationship between the amygdala subregions and CLBP has not yet been delineated. This study aimed to analyze whether the amygdala subregions were linked to the development of CLBP. Methods: A total of 45 patients with CLBP and 45 healthy controls (HCs) were included in this study. All subjects were asked to complete a three-dimensional T1-weighted magnetic resonance imaging (3D-T1 MRI) scan. FreeSurfer 7.3.2 was applied to preprocess the structural MRI images and segment the amygdala into nine subregions. Afterwards, comparisons were made between the two groups in terms of the volumes of the amygdala subregions. Correlation analysis is utilized to examine the relationship between the amygdala subregion and the scale scores, as well as the pain duration in patients with CLBP. Additionally, logistic regression was used to explore the risk of the amygdala and its subregions for CLBP. Results: In comparison to HCs, patients with CLBP exhibited a significant enlargement of the left central nucleus (Ce) and left cortical nucleus (Co). Furthermore, the increased volume of the left Ce was associated with a higher risk of CLBP. Conclusion: Our study suggests that the left Ce and left Co may be involved in the pathophysiological processes of CLBP. Moreover, the volume of the left Ce may be a biomarker for detecting the risk of CLBP.

Altered cortical thickness and structural covariance networks in chronic low back pain.

BACKGROUND: Despite regional brain structural changes having been reported in patients with chronic low back pain (CLBP), the topological properties of structural covariance networks (SCNs), which refer to the organization of the SCNs, remain unclear. This study applied graph theoretical analysis to explore the alterations of the topological properties of SCNs, aiming to comprehend the integration and separation of SCNs in patients with CLBP. METHODS: A total of 38 patients with CLBP and 38 healthy controls (HCs), balanced for age and sex, were scanned using three-dimensional T1-weighted magnetic resonance imaging. The cortical thickness was extracted from 68 brain regions, according to the Desikan-Killiany atlas, and used to reconstruct the SCNs. Subsequently, graph theoretical analysis was employed to evaluate the alterations of the topological properties in the SCNs of patients with CLBP. RESULTS: In comparison to HCs, patients with CLBP had less cortical thickness in the left superior frontal cortex. Additionally, the cortical thickness of the left superior frontal cortex was negatively correlated with the Visual Analogue Scale scores of patients with CLBP. Furthermore, patients with CLBP, relative to HCs, exhibited lower global efficiency and small-worldness, as well as a longer characteristic path length. This indicates a decline in the brain's capacity to transmit and process information, potentially impacting the processing of pain signals in patients with CLBP and contributing to the development of CLBP. In contrast, there were no significant differences in the clustering coefficient, local efficiency, nodal efficiency, nodal betweenness centrality, or nodal degree between the two groups. CONCLUSIONS: From the regional cortical thickness to the complex brain network level, our study demonstrated changes in the cortical thickness and topological properties of the SCNs in patients with CLBP, thus aiding in a better understanding of the pathophysiological mechanisms of CLBP.

Knowledge, attitude, and practice of healthcare professionals toward cognitive dysfunction in Parkinson's disease and cognitive rehabilitation.

BACKGROUND: To investigate the knowledge, attitude, and practice (KAP) of healthcare professionals regarding cognitive dysfunction and cognitive rehabilitation in Parkinson's disease (PD). METHODS: This multicenter, cross-sectional survey enrolled physicians and nurses in 10 hospitals between October 2022 and November 2022. A self-administered questionnaire was developed to collect the demographic information of the participants and their knowledge, attitude, and practice toward cognitive dysfunction in PD and cognitive rehabilitation. RESULTS: This study enrolled 224 physicians and 229 nurses. The knowledge, attitude, and practice scores were 12.57 ± 3.76 (total score: 22), 29.10 ± 3.71 (total score: 32), and 21.07 ± 8.03 (total score: 28) among physicians, and 9.97 ± 4.70 (total score: 22), 25.27 ± 8.96 (total score: 32), and 25.27 ± 8.96 (total score: 28) among nurses. Among physicians, the knowledge scores (OR = 4.23, 95%CI: 2.36-7.58, P < 0.001) and attitude scores (OR = 3.00, 95%CI: 1.67-5.37, P < 0.001) were independently associated with good practice. Among nurses, the knowledge scores (OR = 4.31, 95%CI: 2.31-8.05, P < 0.001), attitude scores (OR = 5.18, 95%CI: 2.82-9.53, P < 0.001), working department (Ref: rehabilitation; neurology: OR = 2.26, 95%CI: 1.01-5.08, P = 0.048; public health service/chronic disease follow-up center: OR = 2.98, 95%CI: 1.12-7.92, P = 0.028) were independently associated with good practice. CONCLUSIONS: Physicians and nurses have insufficient knowledge, favorable attitudes, and active practice regarding cognitive dysfunction and cognitive rehabilitation in PD. This study identified gaps in KAP and suggested education activities to improve the KAP toward cognitive dysfunction in PD.

Factors correlated with excessive daytime sleepiness in patients with Parkinson's disease: A polysomnography study.

OBJECTIVE: To explore the factors correlated with excessive daytime sleepiness (EDS) in patients with Parkinson's disease (PD). METHODS: A total of 239 PD patients were divided into two groups based on the presence of EDS (Epworth Sleepiness Scale score≥10) (PD-EDS vs. PD-non-EDS). Participants underwent an extensive assessment to determine demographic features, disease severity, polysomnography characteristics, and nonmotor symptoms. RESULTS: Of the 239 patients, 56 patients (23.4%) were classified as having PD combined with EDS. Binary logistic regression analysis showed that fatigue (Fatigue Severity Scale [FSS] score ≥4) (odds ratio [OR] [95% CI] = 4.897 [2.376-10.095], p < .001) and the respiratory-related microarousal index (OR [95% CI] = 2.063 [1.085-3.923], p = .027) were independent risk factors for EDS in PD patients. A priori-determined stratified analysis showed that after adjustment for confounding factors, the association of the respiratory-related microarousal index with EDS was significant (OR = 4.404, 95% CI 1.673-11.592, p trend = .036) in patients with respiratory arousal index scores in the highest quintile compared with those with scores in the lowest quintile. CONCLUSION: Our data revealed a close association among the respiratory-related microarousal index, FSS scores, and EDS. It can be speculated that fragmented sleep and pathological abnormalities of the central nervous system resulting in changes in arousal are major influencing factors of EDS in PD.

Effect of cerebral small vessel disease on cognitive impairment in Parkinson's disease.

OBJECTIVES: To explore the association between cerebral small vessel disease (cSVD) and cognitive impairment (CI) in Parkinson's disease (PD). METHODS: 81 PD patients were recruited into the study from September 2018 to December 2020. The demographic characteristics and radiologic and laboratory data were collected. Cognitive assessments were carried out using the Montreal Cognitive Assessment. The association between cSVD and cognitive impairment was analyzed using univariate and binary logistic regression analysis. RESULTS: The binary logistic regression analysis showed that, after correcting for age, educational years, hyperhomocysteinemia, hypertension, and diabetes mellitus, total cSVD scores (OR 1.55, 95% CI 1.07-2.27, P = 0.02), the presence of paraventricular white matter hyperintensity (PVH) (OR 11.78, 95% CI 3.08-45.01, P < 0.001), white matter hyperintensity (WMH) (OR 7.95, 95% CI 2.28-27.79, P = 0.001), and perivascular space (PVS) (OR 6.66, 95% CI 2.08-21.40, P = 0.001) were independent risk factors for PD-CI. CONCLUSION: The presence of cSVD was associated with cognitive dysfunction in patients with PD. It may be beneficial to manage cSVD to prevent the progression of cognitive impairment in patients with PD.

Theory of mind and facial emotion recognition in adults with temporal lobe epilepsy: A meta-analysis.

Background: Mounting studies have investigated impairments in social cognitive domains (including theory of mind [ToM] and facial emotion recognition [FER] in adult patients with temporal lobe epilepsy (TLE). However, to date, inconsistent findings remain. Methods: A search of PubMed, Web of Science, and Embase databases was conducted until December 2021. Hedges g effect sizes were computed with a random-effects model. Meta-regressions were used to assess the potential confounding factors of between-study variability in effect sizes. Results: The meta-analysis included 41 studies, with a combined sample of 1,749 adult patients with TLE and 1,324 healthy controls (HCs). Relative to HCs, adult patients with TLE showed large impairments in ToM (g = -0.92) and cognitive ToM (g = -0.92), followed by medium impairments in affective ToM (g = -0.79) and FER (g = -0.77). Besides, no (statistically) significant differences were observed between the magnitude of social cognition impairment in adult with TLE who underwent and those who did not undergo epilepsy surgery. Meta-regressions exhibited that greater severity of executive functioning was associated with more severe ToM defects, and older age was associated with more severe FER defects. Conclusions: Results of this meta-analysis suggest that adult patients with TLE show differential impairments in the core aspects of social cognitive domains (including ToM and FER), which may help in planning individualized treatment with appropriate cognitive and behavioral interventions.

Social cognition in children and adolescents with epilepsy: A meta-analysis.

Many studies have investigated impairments in two key domains of social cognition (theory of mind [ToM] and facial emotion recognition [FER]) in children and adolescents with epilepsy. However, inconsistent conclusions were found. Our objective was to characterize social cognition performance of children and adolescents with epilepsy. A literature search was conducted using Web of Science, PubMed, and Embase databases. The article retrieval, screening, quality assessment (Newcastle-Ottawa-Scale), and data extraction were performed independently by two investigators. A random-effects model was used to examine estimates. The meta-analysis included 19 studies, with a combined sample of 623 children and adolescents with epilepsy (mean [SD] age, 12.13 [2.62] years; 46.1% female) and 677 healthy controls [HCs]) (mean [SD] age, 11.48 [2.71] years; 50.7% female). The results revealed that relative to HCs, children and adolescents with epilepsy exhibited deficits in ToM (g = -1.08, 95% CI [-1.38, -0.78], p < 0.001, the number of studies [k] = 13), FER (g = -0.98, 95% CI [-1.33, -0.64], p < 0.001, k = 12), and ToM subcomponents (cognitive ToM: g = -1.04, 95% CI [-1.35, -0.72], p < 0.001, k = 12] and affective ToM: g = -0.73, 95% CI [-1.12, -0.34], p < 0.001, k = 8). In addition, there were no statistically significant differences in social cognition deficits between children and adolescents with focal epilepsy and generalized epilepsy. Meta-regressions confirmed the robustness of the results. These quantitative results further deepen our understanding of the two core domains of social cognition in children and adolescents with epilepsy and may assist in the development of cognitive interventions for this patient population. Systematic review registration: https://inplasy.com/inplasy-2022-3-0011/, identifier INPLASY202230011.

Selenium Alleviates Cerebral Ischemia/Reperfusion Injury by Regulating Oxidative Stress, Mitochondrial Fusion and Ferroptosis.

To clarify the potential role of selenium (Se) on cerebral ischemia/reperfusion (I/R) injury, we utilized mouse middle cerebral artery occlusion (MCAO) followed by reperfusion as an animal model and oxygen-glucose deprivation and reoxygenation (OGD/R) to treat N2a cells as a cell model, respectively. MCAO model was established in mice and then divided into different groups with or without Se treatment. TTC staining was used to observe whether the cerebral I/R modeling was successful, and the apoptosis level was determined by TUNEL staining. The expression of GPx-4 and p22phox was assessed by western blot. In vitro experiments, the OGD/R induced oxidative stress in N2a cells was assessed by levels of GSH/GSSG, malondialdehyde, superoxide dismutase and iron content, respectively. QRT-PCR was used to detect the mRNA levels of Cox-2, Fth1, Mfn1 and mtDNA in N2a cells. JC-1 staining and flow cytometry was performed to detect the mitochondrial membrane potential. Se treatment alleviated cerebral I/R injury and improved the survival rate of mice. Additionally, Se treatment apparently attenuated oxidative stress and inhibited iron accumulation in MCAO model mice and OGD/R model of N2a cells. In terms of its mechanism, Se could up-regulate Mfn1 expression to alleviate oxidative stress and ferroptosis by promoting mitochondrial fusion in vivo and vitro. These findings suggest that Se may have great potential in alleviating cerebral I/R injury.

Correlation Between Intracranial Carotid Artery Calcification and Prognosis of Acute Ischemic Stroke After Intravenous Thrombolysis.

Objective: To investigate the correlation between prognosis and intracranial carotid artery calcification (ICAC) in patients with acute ischemic stroke (AIS) who receive intravenous thrombolysis (IVT). Methods: A total of 156 AIS patients who received IVT from March 2019 to March 2020 were enrolled. The modified Woodcock visual score was used to evaluate ICAC in nonenhanced head CT scans. Patients were divided into high calcification burden (HCB; score ≥3) and low calcification burden (LCB; score <3) groups. Demographic, laboratory, imaging and clinical data were compared between the two groups, and whether HCB was a prognostic factor was evaluated. Results: Compared with the LCB group, the HCB group had a higher incidence of atrial fibrillation (49.2 vs.22.1%, P < 0.001) and coronary heart disease (24.6 vs. 10.0%, P = 0.019) and higher serum homocysteine [15.31 (12.15, 17.50) vs. 14.40 (11.20, 16.20), P = 0.036] and hemoglobin A1c (6.93 ± 1.77 vs. 6.37 ± 0.74, P = 0.023) levels. Binary logistic regression analysis showed that atrial fibrillation (OR = 3.031, 95% CI: 1.312-7.006, P = 0.009) and HbA1c (OR = 1.488, 95% CI: 1.050-2.109, P = 0.026) were independent risk factors for ICAC. After adjusting for other risk factors, symptomatic-side and bilateral ICACs were independent risk factors for poor prognosis (OR = 1.969, 95% CI: 1.220-3.178, P = 0.006), (OR = 1.354, 95% CI: 1.065-1.722, P = 0.013) and mortality (OR = 4.245, 95% CI: 1.114-16.171, P = 0.034), (OR = 2.414, 95% CI = 1.152-5.060, P = 0.020) in patients with AIS who received IVT. Conclusion: ICAC is closely related to the prognosis of acute ischemic stroke after intravenous thrombolysis.

Theory of Mind and Empathy in Adults With Epilepsy: A Meta-Analysis.

Mounting evidence suggests that social cognitive abilities [including theory of mind (ToM) and empathy] are impaired in adult patients with epilepsy. Although the deficits in overall ToM in epilepsy have been documented well, the effects of epilepsy on empathic ability and specific subcomponents of ToM remain unclear. The primary aim of this study was to provide the first meta-analytic integration of ToM and empathy in adult patients with epilepsy, and to decompose these constructs to clearly differentiate their distinct (cognitive ToM and affective empathy) and overlapping (affective ToM/cognitive empathy) components. This meta-analysis included 28 studies. Adult patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) showed impairments in cognitive ToM and affective ToM/cognitive empathy compared to the healthy controls (HCs); no group differences were identified for affective empathy. Besides, cognitive ToM was impaired in adult patients with idiopathic generalized epilepsy (IGE) and focal seizures (caused by epileptogenic foci) outside the temporal and frontal lobes (extra-TLE/FLE) and no group differences were evident for affective ToM/cognitive empathy compared to the HCs. Moreover, relative to the HCs, no group differences were identified for affective empathy in adult patients with IGE. Additionally, no (statistically) significant difference was observed between the magnitude of ToM/empathy impairment in adult patients who underwent and those who did not undergo epilepsy surgery. These quantitative findings suggest differential impairment of the core aspects of social cognitive processing in adult patients with epilepsy, which may contribute to the development of structured cognitive interventions (i.e., social cognitive training) for adult patients with epilepsy.

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Social cognition in multiple sclerosis and its subtypes: A meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated demyelinating disease that disrupts several social cognitive abilities, including the theory of mind (ToM) and facial emotion recognition (FER). It is unclear how specific ToM subcomponents, including cognitive and affective ToM, are affected in patients with MS and the social cognitive abilities in MS subtypes. METHODS: A search of PubMed, Web of Science, and Embase databases was conducted until June 2020. Effect sizes were calculated using Hedges g with a random-effects model. RESULTS: A total of 45 studies were included. Relative to health controls (HCs), patients with MS and its subtypes (including relapsing-remitting MS [RRMS] and progressive MS) exhibited impairments in ToM (g = -0.77, g = -0.70, g = -0.75, respectively), cognitive ToM (g = -0.72, g = -0.83, g = -0.73, respectively), affective ToM (g = -0.84, g = -0.63, g = -0. 50, respectively), and FER (g = -0.62, g = -0.53, g = -1.07, respectively). In addition, there was no difference between progressive primary MS and secondary progressive MS in overall ToM, cognitive ToM, affective ToM, and FER. Compared to patients with RRMS, patients with progressive MS showed no difference in overall ToM, cognitive ToM, and affective ToM but had more serious defects in FER (g = -0.57). CONCLUSIONS: These quantitative results indicate that patients with MS and its subtypes have a differential impairment of the core aspects of social cognitive processing (including ToM and FER), which may help develop the structured social cognitive interventions in MS.

MicroRNA-532-5p protects against cerebral ischemia-reperfusion injury by directly targeting CXCL1.

We investigated the function of microRNA (miR)-532-5p in cerebral ischemia-reperfusion injury (CI/RI) and the underlying mechanisms using oxygen-glucose deprivation and reperfusion (OGD/R)-treated SH-SY5Y cells and middle cerebral artery occlusion (MCAO) model rats. MiR-532-5p levels were significantly downregulated in OGD/R-treated SH-SY5Y cells and the brain tissues of MCAO model rats. MiR-532-5p overexpression significantly reduced apoptosis, reactive oxygen species (ROS), and inflammation in the OGD/R-induced SH-SY5Y cells. Bioinformatics analysis using the targetscan and miRDB databases as well as dual luciferase reporter assays confirmed that miR-532-5p directly binds to the 3'UTR of C-X-C Motif Ligand 1 (CXCL1). Methylation-specific PCR (MSP) analysis showed that miR-532-5p expression was reduced in OGD/R-treated SH-SY5Y cells because of miR-532-5p promoter hypermethylation. Moreover, 5-azacytidine, a methylation inhibitor, restored miR-532-5p expression in OGD/R-treated SH-SY5Y cells. Brain tissues of MCAO model rats showed significantly increased cerebral infarction areas, cerebral water, neuronal apoptosis, and activated CXCL1/CXCR2/NF-κB signaling, but these effects were alleviated by intraventricular injection of miR-532-5p agomir. These findings demonstrate that miR-532-5p overexpression significantly reduces in vitro and in vivo CI/RI by targeting CXCL1. Thus, miR-532-5p is a potential therapeutic target for patients with CI/RI.

Empathy and Theory of Mind in Multiple Sclerosis: A Meta-Analysis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Studies have shown that MS disrupts several social cognitive abilities [including empathy and theory of mind (ToM)]. Overall ToM deficits in MS are well documented, but how the specific ToM subcomponents and empathic capacity are affected remains unclear. For this meta-analysis, we searched PubMed, Web of Science, and Embase from inception to July 2020. Effect sizes were calculated using Hedges g with a random-effects model. Thirty-three studies were included. Relative to healthy controls (HCs), patients with MS were moderately impaired in overall empathy (g = -0.67), overall ToM (g = -74), cognitive ToM (g = -0.72), and the overlapping domains of cognitive empathy/affective ToM (g = -0.79); no group differences were identified for affective empathy (g = -0.19). Compared with HCs, patients with relapsing-remitting MS (RRMS) and progressive MS were impaired in overall empathy, overall ToM, cognitive ToM, and cognitive empathy/affective ToM, without significant RRMS-progressive MS differences in impairment degree. We conducted the first meta-analytic review investigating the empathy and ToM functioning patterns in patients with MS and examined the overlapping and distinct subcomponents of these constructs. The findings suggest differential impairment of the core aspects of social cognitive processing in patients with MS, which may importantly inform the development of structured social cognitive MS interventions.

Grey matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

Brain structural abnormalities in idiopathic restless legs syndrome have long been debated. Voxel-based morphometry is an objective structural magnetic resonance imaging technique to investigate regional grey matter volume or density differences between groups. In the last decade, voxel-based morphometry studies have exhibited inconsistent and conflicting findings regarding the presence and localization of brain grey matter alterations in restless legs syndrome. We therefore conducted a coordinate-based meta-analysis to quantitatively examine whether there were consistent grey matter findings in restless legs syndrome using the latest algorithms, seed-based d mapping with permutation of subject images. We included 12 voxel-based morphometry studies (13 datasets, 375 patients and 385 healthy controls). Our coordinate-based meta-analysis did not identify evidence of consistent grey matter alterations in restless legs syndrome. Grey matter alterations via voxel-based morphometry analysis are not therefore recommended to be used as a reliable surrogate neuroimaging marker for restless legs syndrome. This lack of consistency may be attributed to differences in sample size, genetics, gender distribution and age at onset, clinical heterogeneity (clinical course, anatomical distribution of symptoms, disease severity, disease duration, abnormal sensory profiles and comorbidity), and variations in imaging acquisition, data processing and statistical strategies. Longitudinal studies with multimodal neuroimaging techniques are needed to determine whether structural changes are dynamic and secondary to functional abnormalities.

Retinal nerve fiber layer changes in migraine: a systematic review and meta-analysis.

BACKGROUND: Migraine is one of the most common disabling diseases in the world. Its recurrent attacks may lead to abnormalities in the structure of the brain and retina. An increasing number of studies have investigated retinal nerve fiber layer (RNFL) thickness alterations in migraine by the optical coherence tomography (OCT); however, no consensus has yet reached. METHOD: We searched Pubmed, Embase, and Web of Science databases to identify studies that investigated RNFL thickness in migraine by OCT measurement and performed a meta-analysis of eligible studies. RESULTS: Twenty-six studies were included in the meta-analysis, comprising 1530 migraine patients and 1105 healthy controls. The mean RNFL thickness was thinner in the migraine group compared to the control group (SMD =- 0.53). In the subgroup analyses, RNFL thickness were decreased most significantly in the superior (SMD = - 0.71) and inferior (SMD = - 0.63) quadrants among all quadrants. Migraine with aura (SMD = - 0.91) showed a greater effect size of RNFL thickness reduction than migraine without aura (SMD =- 0.47). Spectral-domain OCT (SMD = - 0.55) seems more sensitive to detect RNFL thickness reduction than time-domain OCT (SMD = - 0.44). In addition, age, sex, disease duration, attack frequency, and intraocular pressure were not significantly associated with RNFL thickness. CONCLUSIONS: The findings from our comprehensive meta-analysis with large datasets strengthen the clinical evidence of the RNFL thickness reduction in migraine. RNFL thickness via spectral-domain OCT measurement demonstrates the potential role in differentiating patients with migraine, especially migraine with aura, from healthy controls.

Cortical thickness in Parkinson's disease: a coordinate-based meta-analysis.

Parkinson's disease (PD) is a common age-related neurodegenerative disease that affects the structural architecture of the cerebral cortex. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis is a popular measure to assess brain structural alterations in the gray matter in PD. However, the results of CTh analysis in PD lack consistency and have not been systematically reviewed. We conducted a comprehensive coordinate-based meta-analysis (CBMA) of 38 CTh studies (57 comparison datasets) in 1,843 patients with PD using the latest seed-based d mapping software. Compared with 1,172 healthy controls, no significantly consistent CTh alterations were found in patients with PD, suggesting CTh as an unreliable neuroimaging marker for PD. The lack of consistent CTh alterations in PD could be ascribed to the heterogeneity in clinical populations, variations in imaging methods, and underpowered small sample sizes. These results highlight the need to control for potential confounding factors to produce robust and reproducible CTh results in PD.

Focusing on Comorbidity-A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders.

BACKGROUND: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. OBJECTIVES: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities. METHODS: The novel approach consists of a modification of Seed-based d Mapping-with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults. DISCUSSION: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools.

Blood neurofilament light chain in Parkinson disease and atypical parkinsonisms: A protocol for systematic review and meta-analysis.

BACKGROUND: Neurofilament light chain (NfL), an index of neuroaxonal injury, is a promising diagnostic and prognostic fluid biomarker with high translational value in many neurodegenerative disorders. Blood NfL measurement has been an exciting and active field of research in idiopathic Parkinson disease (PD) and atypical parkinsonisms. However, blood NfL levels in these parkinsonisms from existing literature were inconsistent. No comprehensive meta-analysis has ever been conducted. METHODS: Three major biomedical electronic databases PubMed, Embase, and Web of Science were comprehensively searched from inception to July 10, 2020. This protocol will be prepared based on the guidelines recommended by the statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Original observational studies that measured blood (serum/plasma) NfL concentrations in patients with parkinsonisms (multiple system atrophy [MSA], progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], and dementia with Lewy bodies [DLB]), and healthy controls (HCs) will be included. Quality assessment of the included studies will be performed using the Newcastle Ottawa Scale (NOS). Meta-analyses will be conducted using the STATA software version 13.0. The standardized mean differences as the measure of effect size and 95% confidence intervals were calculated for each comparison of blood NfL levels. Heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be carried out to test the robustness of the results. RESULTS: The meta-analysis will obtain the effect sizes of blood NfL levels in the following comparisons: PD versus HC, MSA versus HC, PSP versus HC, CBS versus HC, DLB versus HC, MSA versus PD, PSP versus PD, CBS versus PD, and DLB versus PD. CONCLUSIONS: The present meta-analysis will provide the quantitative evidence of NfL levels in idiopathic PD and atypical parkinsonisms, hoping to facilitate differential diagnoses in clinical practice. REGISTRATION NUMBER: INPLASY202070091.

Retinal nerve fiber layer changes in migraine: A protocol for systematic review and meta-analysis.

BACKGROUND: Migraine is a common neurological disease, which seriously affects the quality of life and daily activities of patients. Although migraine is a transient phenomenon of cerebral vasoconstriction, it is well documented that recurrent attacks of migraine may lead to abnormalities in retinal structure. Optical coherence tomography (OCT) is a sensitive method to detect subtle damage in retinal nerve fiber layer (RNFL). There have been many studies investigating the difference in RNFL thickness with optical coherence tomography (OCT) between migraine patients and healthy controls. However, the results were not consistent. Our purpose is to perform a meta-analysis to investigate RNFL alterations in migraine. METHODS: We will search PubMed, Embase, Web of science for studies assessing the differences in RNFL measured by OCT between patients with migraine and healthy controls. Case-control studies published in English will be included. Two reviewers will independently screen eligible articles, extract data, and assess quality. This meta-analysis will synthesize selected research data and compare the difference in RNFL thickness between patients with migraine and healthy controls. We will use Stata 15 in this meta-analysis. I statistics will be used to assess heterogeneity. If I ≤ 50%, the data are synthesized will use a fixed effect model. Otherwise, a random effect model will be performed. Publication bias will be determined by the Egger test. The methodological quality of all included studies will be evaluated by the Newcastle-Ottawa Scale (NOS). We will perform subgroup analysis, sensitivity analysis, and meta-regression analysis to test the robustness of the results. RESULTS: We will obtain quantitative results regarding the difference in RNFL thickness between migraine patients and healthy controls. The results will be published in a peer-reviewed journal. CONCLUSIONS: The results of this study provide a high-quality synthesis of existing evidence and provide a basis for assessing the effect of migraine on the thickness of RNFL. REGISTRATION NUMBER: INPLASY 202060033.