Spontaneous brain activity abnormalities in migraine: A meta-analysis of functional neuroimaging.

Neuroimaging studies have demonstrated that migraine is accompanied by spontaneous brain activity alterations in specific regions. However, these findings are inconsistent, thus hindering our understanding of the potential neuropathology. Hence, we performed a quantitative whole-brain meta-analysis of relevant resting-state functional imaging studies to identify brain regions consistently involved in migraine. A systematic search of studies that investigated the differences in spontaneous brain activity patterns between migraineurs and healthy controls up to April 2022 was conducted. We then performed a whole-brain voxel-wise meta-analysis using the anisotropic effect size version of seed-based d mapping software. Complementary analyses including jackknife sensitivity analysis, heterogeneity test, publication bias test, subgroup analysis, and meta-regression analysis were conducted as well. In total, 24 studies that reported 31 datasets were finally eligible for our meta-analysis, including 748 patients and 690 controls. In contrast to healthy controls, migraineurs demonstrated consistent and robust decreased spontaneous brain activity in the angular gyrus, visual cortex, and cerebellum, while increased activity in the caudate, thalamus, pons, and prefrontal cortex. Results were robust and highly replicable in the following jackknife sensitivity analysis and subgroup analysis. Meta-regression analyses revealed that a higher visual analog scale score in the patient sample was associated with increased spontaneous brain activity in the left thalamus. These findings provided not only a comprehensive overview of spontaneous brain activity patterns impairments, but also useful insights into the pathophysiology of dysfunction in migraine.

Computed tomography-based radiomics machine learning classifiers to differentiate type I and type II epithelial ovarian cancers.

OBJECTIVES: To compare computed tomography (CT)-based radiomics for preoperatively differentiating type I and II epithelial ovarian cancers (EOCs) using different machine learning classifiers and to construct and validate the best diagnostic model. METHODS: A total of 470 patients with EOCs were included retrospectively. Patients were divided into a training dataset (N = 329) and a test dataset (N = 141). A total of 1316 radiomics features were extracted from the portal venous phase of contrast-enhanced CT images for each patient, followed by dimension reduction of the features. The support vector machine (SVM), k-nearest neighbor (KNN), random forest (RF), naïve Bayes (NB), logistic regression (LR), and eXtreme Gradient Boosting (XGBoost) classifiers were trained to obtain the radiomics signatures. The performance of each radiomics signature was evaluated and compared by the area under the receiver operating characteristic curve (AUC) and relative standard deviation (RSD). The best radiomics signature was selected and combined with clinical and radiological features to establish a combined model. The diagnostic value of the combined model was assessed. RESULTS: The LR-based radiomics signature performed well in the test dataset, with an AUC of 0.879 and an accuracy of 0.773. The combined model performed best in both the training and test datasets, with AUCs of 0.900 and 0.934 and accuracies of 0.848 and 0.823, respectively. CONCLUSION: The combined model showed the best diagnostic performance for distinguishing between type I and II EOCs preoperatively. Therefore, it can be a useful tool for clinical individualized EOC classification. KEY POINTS: • Radiomics features extracted from computed tomography (CT) could be used to differentiate type I and II epithelial ovarian cancers (EOCs). • Machine learning can improve the performance of differentiating type I and II EOCs. • The combined model exhibited the best diagnostic capability over the other models in both the training and test datasets.

Voxel- and tensor-based morphometry with machine learning techniques identifying characteristic brain impairment in patients with cervical spondylotic myelopathy.

Aim: The diagnosis of cervical spondylotic myelopathy (CSM) relies on several methods, including x-rays, computed tomography, and magnetic resonance imaging (MRI). Although MRI is the most useful diagnostic tool, strategies to improve the precise and independent diagnosis of CSM using novel MRI imaging techniques are urgently needed. This study aimed to explore potential brain biomarkers to improve the precise diagnosis of CSM through the combination of voxel-based morphometry (VBM) and tensor-based morphometry (TBM) with machine learning techniques. Methods: In this retrospective study, 57 patients with CSM and 57 healthy controls (HCs) were enrolled. The structural changes in the gray matter volume and white matter volume were determined by VBM. Gray and white matter deformations were measured by TBM. The support vector machine (SVM) was used for the classification of CSM patients from HCs based on the structural features of VBM and TBM. Results: CSM patients exhibited characteristic structural abnormalities in the sensorimotor, visual, cognitive, and subcortical regions, as well as in the anterior corona radiata and the corpus callosum [P < 0.05, false discovery rate (FDR) corrected]. A multivariate pattern classification analysis revealed that VBM and TBM could successfully identify CSM patients and HCs [classification accuracy: 81.58%, area under the curve (AUC): 0.85; P < 0.005, Bonferroni corrected] through characteristic gray matter and white matter impairments. Conclusion: CSM may cause widespread and remote impairments in brain structures. This study provided a valuable reference for developing novel diagnostic strategies to identify CSM.

Schizophrenia mediating the effect of smoking phenotypes on antisocial behavior: A Mendelian randomization analysis.

AIMS: Previous studies have indicated that smoking is linked to an increased risk of developing schizophrenia, and that individuals with schizophrenia are more prone to engaging in antisocial behavior. However, the causal effects of smoking behaviors on antisocial behavior and the potential mediating role of schizophrenia remains largely unclear. METHODS: In the present study, using the summary data from genome wide association studies of smoking phenotypes (N = 323,386-805,431), schizophrenia (Ncases = 53,386, Ncontrols = 77,258), and antisocial behavior (N = 85,359), we assessed bidirectional causality between smoking phenotypes and schizophrenia by the Mendelian randomization (MR) approach. Using a two-step MR approach, we further examined whether causal effects of smoking phenotypes/schizophrenia on antisocial behavior were mediated by schizophrenia/smoking phenotypes. RESULTS: The results showed that smoking initiation (SmkInit) and age of smoking initiation (AgeSmk) causally increase the risk of schizophrenia (SmkInit: OR = 2.06, 95% CI = 1.77-2.39, p = 4.36 × 10-21 ; AgeSmk: OR = 0.32, 95% CI = 0.16-0.62, p = 8.11 × 10-4 , Bonferroni corrected). However, there was no causal effect that liability to schizophrenia leads to smoking phenotypes. MR evidence also revealed causal influences of SmkInit and the amount smoked (CigDay) on antisocial behavior (SmkInit: OR = 1.28, 95% CI = 1.17-1.41, p = 2.53 × 10-7 ; CigDay: OR = 1.16, 95% CI = 1.06-1.27, p = 1.60 × 10-3 , Bonferroni corrected). Furthermore, the mediation analysis indicated that the relationship between SmkInit and antisocial behavior was partly mediated by schizophrenia (mediated proportion = 6.92%, 95% CI = 0.004-0.03, p = 9.66 × 10-3 ). CONCLUSIONS: These results provide compelling evidence for taking smoking interventions as a prevention strategy for schizophrenia and its related antisocial behavior.

Mapping the landscape: a bibliometric analysis of resting-state fMRI research on schizophrenia over the past 25 years.

Schizophrenia, a multifaceted mental disorder characterized by disturbances in thought, perception, and emotion, has been extensively investigated through resting-state fMRI, uncovering changes in spontaneous brain activity among those affected. However, a bibliometric examination regarding publication trends in resting-state fMRI studies related to schizophrenia is lacking. This study obtained relevant publications from the Web of Science Core Collection spanning the period from 1998 to 2022. Data extracted from these publications included information on countries/regions, institutions, authors, journals, and keywords. The collected data underwent analysis and visualization using VOSviewer software. The primary analyses included examination of international and institutional collaborations, authorship patterns, co-citation analyses of authors and journals, as well as exploration of keyword co-occurrence and temporal trend networks. A total of 859 publications were retrieved, indicating an overall growth trend from 1998 to 2022. China and the United States emerged as the leading contributors in both publication outputs and citations, with Central South University and the University of New Mexico being identified as the most productive institutions. Vince D. Calhoun had the highest number of publications and citation counts, while Karl J. Friston was recognized as the most influential author based on co-citations. Key journals such as Neuroimage, Schizophrenia Research, Schizophrenia Bulletin, and Biological Psychiatry played pivotal roles in advancing this field. Recent popular keywords included support vector machine, antipsychotic medication, transcranial magnetic stimulation, and related terms. This study systematically synthesizes the historical development, current status, and future trends in resting-state fMRI research in schizophrenia, offering valuable insights for future research directions.

Exploring functional dysconnectivity in schizophrenia: alterations in eigenvector centrality mapping and insights into related genes from transcriptional profiles.

Schizophrenia is a mental health disorder characterized by functional dysconnectivity. Eigenvector centrality mapping (ECM) has been employed to investigate alterations in functional connectivity in schizophrenia, yet the results lack consistency, and the genetic mechanisms underlying these changes remain unclear. In this study, whole-brain voxel-wise ECM analyses were conducted on resting-state functional magnetic resonance imaging data. A cohort of 91 patients with schizophrenia and 91 matched healthy controls were included during the discovery stage. Additionally, in the replication stage, 153 individuals with schizophrenia and 182 healthy individuals participated. Subsequently, a comprehensive analysis was performed using an independent transcriptional database derived from six postmortem healthy adult brains to explore potential genetic factors influencing the observed functional dysconnectivity, and to investigate the roles of identified genes in neural processes and pathways. The results revealed significant and reliable alterations in the ECM across multiple brain regions in schizophrenia. Specifically, there was a significant decrease in ECM in the bilateral superior and middle temporal gyrus, and an increase in the bilateral thalamus in both the discovery and replication stages. Furthermore, transcriptional analysis revealed 420 genes whose expression patterns were related to changes in ECM, and these genes were enriched mainly in biological processes associated with synaptic signaling and transmission. Together, this study enhances our knowledge of the neural processes and pathways involved in schizophrenia, shedding light on the genetic factors that may be linked to functional dysconnectivity in this disorder.

CT-Based Radiomics for the Preoperative Prediction of Occult Peritoneal Metastasis in Epithelial Ovarian Cancers.

RATIONALE AND OBJECTIVES: The objective of this study was to develop a comprehensive combined model for predicting occult peritoneal metastasis (OPM) in epithelial ovarian cancers (EOCs) using radiomics features derived from computed tomography (CT) and clinical-radiological predictors. MATERIALS AND METHODS: A total of 224 patients with EOCs were randomly divided into training dataset (N = 156) and test dataset (N = 86). Five clinical factors and seven radiological features were collected. The radiomics features were extracted from CT images of each patient. Multivariate logistic regression was employed to construct clinical and radiological models. The correlation analysis and least absolute shrinkage and selection operator algorithm were used to select radiomics features and build radiomics model. The important clinical, radiological factors, and radiomics features were integrated into a combined model by multivariate logistic regression. Receiver operating characteristics curve with area under the curve (AUC) were used to evaluate and compare predictive performance. RESULTS: Carbohydrate antigen 125 (CA-125) and human epididymal protein 4 (HE-4) were independent clinical predictors. Laterality, thickened septa and margin were independent radiological predictors. In the training dataset, the AUCs for the clinical, radiological and radiomics models in evaluating OPM were 0.759, 0.819, and 0.830, respectively. In the test dataset, the AUCs for these models were 0.846, 0.835, and 0.779, respectively. The combined model outperformed other models in both the training and the test datasets with AUCs of 0.901 and 0.912, respectively. Decision curve analysis indicated that the combined model yielded a higher net benefit compared to the other models. CONCLUSION: The combined model, integrating radiomics features with clinical and radiological predictors exhibited improved accuracy in predicting OPM in EOCs.

Individual-level brain morphological similarity networks: Current methodologies and applications.

AIMS: The human brain is an extremely complex system in which neurons, clusters of neurons, or regions are connected to form a complex network. With the development of neuroimaging techniques, magnetic resonance imaging (MRI)-based brain networks play a key role in our understanding of the intricate architecture of human brain. Among them, the structural MRI-based brain morphological network approach has attracted increasing attention due to the advantages in data acquisition, image quality, and in revealing the structural organizing principles intrinsic to the brain. This review is to summarize the methodology and related applications of individual-level morphological networks. BACKGROUND: There have been a growing number of studies related to brain morphological similarity networks. Conventional morphological networks are intersubject covariance networks constructed using a certain morphological indicator of a group of subjects; individual-level morphological networks, on the other hand, measure the morphological similarity between brain regions for individual brains and can reflect the morphological information of single subjects. In recent years, individual morphological networks have demonstrated significant worth in exploring the topological changes of the human brain under both normal and disease conditions. Such studies provided novel perspectives for understanding human brain development and exploring the pathological mechanisms of neuropsychiatric disorders. CONCLUSION: This paper mainly focuses on the studies of brain morphological networks at the individual level, introduces several ways for network construction, reviews representative work in this field, and finally points out current problems and future directions.

Identifying the mediating role of socioeconomic status on the relationship between schizophrenia and major depressive disorder: a Mendelian randomisation analysis.

Depressive disorder prevalence in patients with schizophrenia has been reported to be 40%. People with low socioeconomic status (SES) are more likely to suffer from schizophrenia and major depressive disorder (MDD). However, the causal relationship between schizophrenia and depression and the potential mediating role of SES remains unclear. Two-sample Mendelian randomization (MR) analyses were conducted to explore the bidirectional causal relationship between schizophrenia and MDD with the largest sample size of European ancestry from public genome-wide association studies (sample size ranged from 130,644 to 480,359). Inverse variance weighted (IVW) method was used as the primary analysis, and several canonical MR methods were used as validation analyses. The mediating role of SES (educational years, household income, employment status, and Townsend deprivation index) was estimated by the two-step MR method. MR analyses showed that genetically predicted schizophrenia was associated with an increased risk of MDD (IVW odds ratio [OR] = 1.137 [95% CI 1.095, 1.181]). Reversely, MDD was also associated with an increased risk of schizophrenia (IVW OR = 1.323 [95% CI 1.118, 1.565]). The mediation analysis via the two-step MR method revealed that the causal effect of schizophrenia on MDD was partly mediated by the Townsend deprivation index with a proportion of 10.27%, but no significant mediation effect was found of SES on the causal effect of MDD on schizophrenia. These results suggest a robust bidirectional causal effect between schizophrenia and MDD. Patients with schizophrenia could benefit from the early and effective intervention of the Townsend deprivation index.

Transcriptional signatures of the whole-brain voxel-wise resting-state functional network centrality alterations in schizophrenia.

Neuroimaging studies have revealed that patients with schizophrenia exhibit disrupted resting-state functional connectivity. However, the inconsistent findings across these studies have hindered our comprehensive understanding of the functional connectivity changes associated with schizophrenia, and the molecular mechanisms associated with these alterations remain largely unclear. A quantitative meta-analysis was first conducted on 21 datasets, involving 1057 patients and 1186 healthy controls, to examine disrupted resting-state functional connectivity in schizophrenia, as measured by whole-brain voxel-wise functional network centrality (FNC). Subsequently, partial least squares regression analysis was employed to investigate the relationship between FNC changes and gene expression profiles obtained from the Allen Human Brain Atlas database. Finally, gene enrichment analysis was performed to unveil the biological significance of the altered FNC-related genes. Compared with healthy controls, patients with schizophrenia show consistently increased FNC in the right inferior parietal cortex extending to the supramarginal gyrus, angular gyrus, bilateral medial prefrontal cortex, and right dorsolateral prefrontal cortex, while decreased FNC in the bilateral insula, bilateral postcentral gyrus, and right inferior temporal gyrus. Meta-regression analysis revealed that increased FNC in the right inferior parietal cortex was positively correlated with clinical score. In addition, these observed functional connectivity changes were found to be spatially associated with the brain-wide expression of specific genes, which were enriched in diverse biological pathways and cell types. These findings highlight the aberrant functional connectivity observed in schizophrenia and its potential molecular underpinnings, providing valuable insights into the neuropathology of dysconnectivity associated with this disorder.

Machine-learning-based contrast-enhanced computed tomography radiomic analysis for categorization of ovarian tumors.

Objectives: This study aims to evaluate the diagnostic performance of machine-learning-based contrast-enhanced CT radiomic analysis for categorizing benign and malignant ovarian tumors. Methods: A total of 1,329 patients with ovarian tumors were randomly divided into a training cohort (N=930) and a validation cohort (N=399). All tumors were resected, and pathological findings were confirmed. Radiomic features were extracted from the portal venous phase images of contrast-enhanced CT. The clinical predictors included age, CA-125, HE-4, ascites, and margin of tumor. Both radiomics model (including selected radiomic features) and mixed model (incorporating selected radiomic features and clinical predictors) were constructed respectively. Six classifiers [k-nearest neighbor (KNN), support vector machines (SVM), random forest (RF), logistic regression (LR), multi-layer perceptron (MLP), and eXtreme Gradient Boosting (XGBoost)] were used for each model. The mean relative standard deviation (RSD) and area under the receiver operating characteristic curve (AUC) were applied to evaluate and select the best classifiers. Then, the performances of the two models with selected classifiers were assessed in the validation cohort. Results: The MLP classifier with the least RSD (1.21 and 0.53, respectively) was selected as the best classifier in both radiomics and mixed models. The two models with MLP classifier performed well in the validation cohort, with the AUCs of 0.91 and 0.96 and with accuracies (ACCs) of 0.83 and 0.87, respectively. The Delong test showed that the AUC of mixed model was statistically different from that of radiomics model (p<0.001). Conclusions: Machine-learning-based CT radiomic analysis could categorize ovarian tumors with good performance preoperatively. The mixed model with MLP classifier may be a potential tool in clinical applications.

Frequency-dependent white-matter functional network changes associated with cognitive deficits in subcortical vascular cognitive impairment.

Vascular cognitive impairment (VCI) refers to all forms of cognitive decline associated with cerebrovascular diseases, in which white matter (WM) is highly vulnerable. Although previous studies have shown that blood oxygen level-dependent (BOLD) signals inside WM can effectively reflect neural activities, whether WM BOLD signal alterations are present and their roles underlying cognitive impairment in VCI remain largely unknown. In this study, 36 subcortical VCI (SVCI) patients and 36 healthy controls were enrolled to evaluate WM dysfunction. Specifically, fourteen distinct WM networks were identified from resting-state functional MRI using K-means clustering analysis. Subsequently, between-network functional connectivity (FC) and within-network BOLD signal amplitude of WM networks were calculated in three frequency bands (band A: 0.01-0.15 Hz, band B: 0.08-0.15 Hz, and band C: 0.01-0.08 Hz). Patients with SVCI manifested decreased FC mainly in bilateral parietal WM regions, forceps major, superior and inferior longitudinal fasciculi. These connections extensively linked with distinct WM networks and with gray-matter networks such as frontoparietal control, dorsal and ventral attention networks, which exhibited frequency-specific alterations in SVCI. Additionally, extensive amplitude reductions were found in SVCI, showing frequency-dependent properties in parietal, anterior corona radiate, pre/post central, superior and inferior longitudinal fasciculus networks. Furthermore, these decreased FC and amplitudes showed significant positive correlations with cognitive performances in SVCI, and high diagnostic performances for SVCI especially combining all bands. Our study indicated that VCI-related cognitive deficits were characterized by frequency-dependent WM functional abnormalities, which offered novel applicable neuromarkers for VCI.

Selective Aberrant Functional-Structural Coupling of Multiscale Brain Networks in Subcortical Vascular Mild Cognitive Impairment.

Subcortical vascular mild cognitive impairment (svMCI) is a common prodromal stage of vascular dementia. Although mounting evidence has suggested abnormalities in several single brain network metrics, few studies have explored the consistency between functional and structural connectivity networks in svMCI. Here, we constructed such networks using resting-state fMRI for functional connectivity and diffusion tensor imaging for structural connectivity in 30 patients with svMCI and 30 normal controls. The functional networks were then parcellated into topological modules, corresponding to several well-defined functional domains. The coupling between the functional and structural networks was finally estimated and compared at the multiscale network level (whole brain and modular level). We found no significant intergroup differences in the functional-structural coupling within the whole brain; however, there was significantly increased functional-structural coupling within the dorsal attention module and decreased functional-structural coupling within the ventral attention module in the svMCI group. In addition, the svMCI patients demonstrated decreased intramodular connectivity strength in the visual, somatomotor, and dorsal attention modules as well as decreased intermodular connectivity strength between several modules in the functional network, mainly linking the visual, somatomotor, dorsal attention, ventral attention, and frontoparietal control modules. There was no significant correlation between the altered module-level functional-structural coupling and cognitive performance in patients with svMCI. These findings demonstrate for the first time that svMCI is reflected in a selective aberrant topological organization in multiscale brain networks and may improve our understanding of the pathophysiological mechanisms underlying svMCI.