Major depressive disorder (MDD) is a mental disorder characterized by at least 2 weeks of low mood, which is present across most situations. Diagnosis of MDD using rest-state functional magnetic resonance imaging (fMRI) data faces many challenges due to the high dimensionality, small samples, noisy and individual variability. To our best knowledge, no studies aim at classification with effective connectivity and functional connectivity measures between MDD patients and healthy controls. In this study, we performed a data-driving classification analysis using the whole brain connectivity measures which included the functional connectivity from two brain templates and effective connectivity measures created by the default mode network (DMN), dorsal attention network (DAN), frontal-parietal network (FPN), and silence network (SN). Effective connectivity measures were extracted using spectral Dynamic Causal Modeling (spDCM) and transformed into a vectorial feature space. Linear Support Vector Machine (linear SVM), non-linear SVM, k-Nearest Neighbor (KNN), and Logistic Regression (LR) were used as the classifiers to identify the differences between MDD patients and healthy controls. Our results showed that the highest accuracy achieved 91.67% (p < 0.0001) when using 19 effective connections and 89.36% when using 6,650 functional connections. The functional connections with high discriminative power were mainly located within or across the whole brain resting-state networks while the discriminative effective connections located in several specific regions, such as posterior cingulate cortex (PCC), ventromedial prefrontal cortex (vmPFC), dorsal cingulate cortex (dACC), and inferior parietal lobes (IPL). To further compare the discriminative power of functional connections and effective connections, a classification analysis only using the functional connections from those four networks was conducted and the highest accuracy achieved 78.33% (p < 0.0001). Our study demonstrated that the effective connectivity measures might play a more important role than functional connectivity in exploring the alterations between patients and health controls and afford a better mechanistic interpretability. Moreover, our results showed a diagnostic potential of the effective connectivity for the diagnosis of MDD patients with high accuracies allowing for earlier prevention or intervention.

The application of deep learning methods in brain disease diagnosis is becoming a new research hotspot. This study constructed brain functional networks based on the functional magnetic resonance imaging (fMRI) data, and proposed a novel convolutional neural network combined with a prototype learning (CNNPL) framework to classify brain functional networks for the diagnosis of autism spectrum disorder (ASD). At the bottom of CNNPL, traditional CNN was employed as the basic feature extractor, while at the top of CNNPL multiple prototypes were automatically learnt on the features to represent different categories. A generalized prototype loss based on distance cross-entropy was proposed to jointly learn the parameters of the CNN feature extractor and the prototypes. The classification was implemented with prototype matching. A transfer learning strategy was introduced to our CNNPL for weight initialization in the subsequent fine-tuning phase to promote model training. We conducted systematic experiments on the aggregate multi-sites ASD dataset. Experimental results revealed that our model outperforms the current state-of-the-art methods in ASD classification and can reliably learn inter-site biomarkers, indicating the robustness of our model on large-scale dataset with inter-site variability. Furthermore, our model demonstrated robust learning capability for high-level organization of brain functionality. Our study also identified important brain regions as biomarkers associated with ASD classification. Together, our proposed model provides a promising solution for learning and classifying brain functional networks, and thus contributes to the biomarker extraction and imaging diagnosis of ASD.

The default mode network (DMN) is thought to reflect endogenous neural activity, which is considered as one of the most intriguing phenomena in cognitive neuroscience. Previous studies have found that key regions within the DMN are highly interconnected. Here, we characterized the genetic influences on causal or directed information flow within the DMN during the resting state. In this study, we recruited 46 pairs of twins and collected fMRI imaging data using a 3.0 T scanner. Dynamic causal modeling was conducted for each participant, and a structural equation model was used to calculate the heritability of DMN in terms of its effective connectivity. Model comparison favored a full-connected model. Structural equal modeling was used to estimate the additive genetics (A), common environment (C) and unique environment (E) contributions to variance for the DMN effective connectivity. The ACE model was preferred in the comparison of structural equation models. Heritability of DMN effective connectivity was 0.54, suggesting that the genetic made a greater contribution to the effective connectivity within DMN. Establishing the heritability of default-mode effective connectivity endorses the use of resting-state networks as endophenotypes or intermediate phenotypes in the search for the genetic basis of psychiatric or neurological illnesses.