Altered Effective Connectivity Among the Cerebellum and Cerebrum in Patients with Major Depressive Disorder Using Multisite Resting-State fMRI.

Major depressive disorder (MDD) is a serious and widespread psychiatric disorder. Previous studies mainly focused on cerebrum functional connectivity, and the sample size was relatively small. However, functional connectivity is undirected. And, there is increasing evidence that the cerebellum is also involved in emotion and cognitive processing and makes outstanding contributions to the symptomology and pathology of depression. Therefore, we used a large sample size of resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate the altered effective connectivity (EC) among the cerebellum and other cerebral cortex in patients with MDD. Here, from the perspective of data-driven analysis, we used two different atlases to divide the whole brain into different regions and analyzed the alterations of EC and EC networks in the MDD group compared with healthy controls group (HCs). The results showed that compared with HCs, there were significantly altered EC in the cerebellum-neocortex and cerebellum-basal ganglia circuits in MDD patients, which implied that the cerebellum may be a potential biomarker of depressive disorders. And, the alterations of EC brain networks in MDD patients may provide new insights into the pathophysiological mechanisms of depression.

The alterations of brain functional connectivity networks in major depressive disorder detected by machine learning through multisite rs-fMRI data.

BACKGROUND: The current diagnosis of major depressive disorder (MDD) is mainly based on the patient's self-report and clinical symptoms. Machine learning methods are used to identify MDD using resting-state functional magnetic resonance imaging (rs-fMRI) data. However, due to large site differences in multisite rs-fMRI data and the difficulty of sample collection, most of the current machine learning studies use small sample sizes of rs-fMRI datasets to detect the alterations of functional connectivity (FC) or network attribute (NA), which may affect the reliability of the experimental results. METHODS: Multisite rs-fMRI data were used to increase the size of the sample, and then we extracted the functional connectivity (FC) and network attribute (NA) features from 1611 rs-fMRI data (832 patients with MDD (MDDs) and 779 healthy controls (HCs)). ComBat algorithm was used to harmonize the data variances caused by the multisite effect, and multivariate linear regression was used to remove age and sex covariates. Two-sample t-test and wrapper-based feature selection methods (support vector machine recursive feature elimination with cross-validation (SVM-RFECV) and LightGBM's "feature_importances_" function) were used to select important features. The Shapley additive explanations (SHAP) method was used to assign the contribution of features to the best classification effect model. RESULTS: The best result was obtained from the LinearSVM model trained with the 136 important features selected by SVMRFE-CV. In the nested five-fold cross-validation (consisting of an outer and an inner loop of five-fold cross-validation) of 1611 data, the model achieved the accuracy, sensitivity, and specificity of 68.90 %, 71.75 %, and 65.84 %, respectively. The 136 important features were tested in a small dataset and obtained excellent classification results after balancing the ratio between patients with depression and HCs. CONCLUSIONS: The combined use of FC and NA features is effective for classifying MDDs and HCs. The important FC and NA features extracted from the large sample dataset have some generalization performance and may be used as a reference for the altered brain functional connectivity networks in MDD.

A strategy of model space search for dynamic causal modeling in task fMRI data exploratory analysis.

Dynamic causal modeling (DCM) is a tool used for effective connectivity (EC) estimation in neuroimage analysis. But it is a model-driven analysis method, and the structure of the EC network needs to be determined in advance based on a large amount of prior knowledge. This characteristic makes it difficult to apply DCM to the exploratory brain network analysis. The exploratory analysis of DCM can be realized from two perspectives: one is to reduce the computational cost of the model; the other is to reduce the model space. From the perspective of model space reduction, a model space exploration strategy is proposed, including two algorithms. One algorithm, named GreedyEC, starts with reducing EC from full model, and the other, named GreedyROI, start with adding EC from one node model. Then the two algorithms were applied to the task state functional magnetic resonance imaging (fMRI) data of visual object recognition and selected the best DCM model from the perspective of model comparison based on Bayesian model compare method. Results show that combining the results of the two algorithms can further improve the effect of DCM exploratory analysis. For convenience in application, the algorithms were encapsulated into MATLAB function based on SPM to help neuroscience researchers to analyze the brain causal information flow network. The strategy provides a model space exploration tool that may obtain the best model from the perspective of model comparison and lower the threshold of DCM analysis.

Aggressive humor style and cyberbullying perpetration: Normative tolerance and moral disengagement perspective.

The literature has acknowledged the correlation between aggressive humor style and cyberbullying perpetration; however, little is known about how this occurs. In this study, we sought to gain an understanding of how and when someone with an aggressive humor style may develop into a perpetrator of cyberbullying. We propose that whether an individual's aggressive humor style results in cyberbullying perpetration depends on online social norms of tolerance for aggressive humor. When online normative tolerance for aggressive humor is high, individuals' aggressive humor style is positively correlated with their moral disengagement, which, in turn, increases their intention to commit cyberbullying. When online normative tolerance for aggressive humor is low, the effect of individuals' aggressive humor style on their moral disengagement is attenuated, which, in turn, weakens the relationship between aggressive humor style and cyberbullying perpetration. A total of 305 Chinese university students were recruited to participate in the experiment, and we found support for this hypothesis across the experiment. Several theoretical and practical implications are discussed.

Altered Effective Connectivity of Children and Young Adults With Unilateral Amblyopia: A Resting-State Functional Magnetic Resonance Imaging Study.

The altered functional connectivity (FC) in amblyopia has been investigated by many studies, but the specific causality of brain connectivity needs to be explored further to understand the brain activity of amblyopia. We investigated whether the effective connectivity (EC) of children and young adults with amblyopia was altered. The subjects included 16 children and young adults with left eye amblyopia and 17 healthy controls (HCs). The abnormalities between the left/right primary visual cortex (PVC) and the other brain regions were investigated in a voxel-wise manner using the Granger causality analysis (GCA). According to the EC results in the HCs and the distribution of visual pathways, 12 regions of interest (ROIs) were selected to construct an EC network. The alteration of the EC network of the children and young adults with amblyopia was analyzed. In the voxel-wise manner analysis, amblyopia showed significantly decreased EC between the left/right of the PVC and the left middle frontal gyrus/left inferior frontal gyrus compared with the HCs. In the EC network analysis, compared with the HCs, amblyopia showed significantly decreased EC from the left calcarine fissure, posterior cingulate gyrus, left lingual gyrus, right lingual gyrus, and right fusiform gyrus to the right calcarine fissure. Amblyopia also showed significantly decreased EC from the right inferior frontal gyrus and right lingual gyrus to the left superior temporal gyrus compared with the HCs in the EC network analysis. The results may indicate that amblyopia altered the visual feedforward and feedback pathway, and amblyopia may have a greater relevance with the feedback pathway than the feedforward pathway. Amblyopia may also correlate with the feedforward of the third visual pathway.