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Major depressive disorder (MDD) is a serious and heterogeneous psychiatric disorder that needs accurate diagnosis. Resting-state functional MRI (rsfMRI), which captures multiple perspectives on brain structure, function, and connectivity, is increasingly applied in the diagnosis and pathological research of MDD. Different machine learning algorithms are then developed to exploit the rich information in rsfMRI and discriminate MDD patients from normal controls. Despite recent advances reported, the MDD discrimination accuracy has room for further improvement. The generalizability and interpretability of the discrimination method are not sufficiently addressed either. Here, we propose a machine learning method (MFMC) for MDD discrimination by concatenating multiple features and stacking multiple classifiers. MFMC is tested on the REST-meta-MDD data set that contains 2428 subjects collected from 25 different sites. MFMC yields 96.9% MDD discrimination accuracy, demonstrating a significant improvement over existing methods. In addition, the generalizability of MFMC is validated by the good performance when the training and testing subjects are from independent sites. The use of XGBoost as the meta classifier allows us to probe the decision process of MFMC. We identify 13 feature values related to 9 brain regions including the posterior cingulate gyrus, superior frontal gyrus orbital part, and angular gyrus, which contribute most to the classification and also demonstrate significant differences at the group level. The use of these 13 feature values alone can reach 87% of MFMC’s full performance when taking all feature values. These features may serve as clinically useful diagnostic and prognostic biomarkers for MDD in the future.

Accumulating evidence showed that major depressive disorder (MDD) is characterized by a dysfunction of serotonin neurotransmission. Raphe nuclei are the sources of most serotonergic neurons that project throughout the brain. Incorporating measurements of activity within the raphe nuclei into the analysis of connectivity characteristics may contribute to understanding how neurotransmitter synthesized centers are involved in the pathogenesis of MDD. Here, we analyzed the resting-state functional magnetic resonance imaging (RS-fMRI) dataset from 1,148 MDD patients and 1,079 healthy individuals recruited across nine centers. A seed-based analysis with the dorsal raphe and median raphe nuclei was performed to explore the functional connectivity (FC) alterations. Compared to controls, for dorsal raphe, the significantly decreased FC linking with the right precuneus and median cingulate cortex were found; for median raphe, the increased FC linking with right superior cerebellum (lobules V/VI) was found in MDD patients. In further exploratory analyzes, MDD-related connectivity alterations in dorsal and median raphe nuclei in different clinical factors remained highly similar to the main findings, indicating these abnormal connectivities are a disease-related alteration. Our study highlights a functional dysconnection pattern of raphe nuclei in MDD with multi-site big data. These findings help improve our understanding of the pathophysiology of depression and provide evidence of the theoretical foundation for the development of novel pharmacotherapies.

Resting-state functional magnetic resonance imaging (rsfMRI) is a powerful tool for investigating the relationship between brain function and cognitive processes as it allows for the functional organization of the brain to be captured without relying on a specific task or stimuli. In this paper, we present a novel modeling architecture called BrainRGIN for predicting intelligence (fluid, crystallized and total intelligence) using graph neural networks on rsfMRI derived static functional network connectivity matrices. Extending from the existing graph convolution networks, our approach incorporates a clustering-based embedding and graph isomorphism network in the graph convolutional layer to reflect the nature of the brain sub-network organization and efficient network expression, in combination with TopK pooling and attention-based readout functions. We evaluated our proposed architecture on a large dataset, specifically the Adolescent Brain Cognitive Development Dataset, and demonstrated its effectiveness in predicting individual differences in intelligence. Our model achieved lower mean squared errors, and higher correlation scores than existing relevant graph architectures and other traditional machine learning models for all of the intelligence prediction tasks. The middle frontal gyrus exhibited a significant contribution to both fluid and crystallized intelligence, suggesting their pivotal role in these cognitive processes. Total composite scores identified a diverse set of brain regions to be relevant which underscores the complex nature of total intelligence., Competing Interests: Financial Disclosures Section All authors declare that they have no conflicts of interest.

Spatial source phase, the phase information of spatial maps extracted from functional magnetic resonance imaging (fMRI) data by data‐driven methods such as independent component analysis (ICA), has rarely been studied. While the observed phase has been shown to convey unique brain information, the role of spatial source phase in representing the intrinsic activity of the brain is yet not clear. This study explores the spatial source phase for identifying spatial differences between patients with schizophrenia (SZs) and healthy controls (HCs) using complex‐valued resting‐state fMRI data from 82 individuals. ICA is first applied to preprocess fMRI data, and post‐ICA phase de‐ambiguity and denoising are then performed. The ability of spatial source phase to characterize spatial differences is examined by the homogeneity of variance test (voxel‐wise F‐test) with false discovery rate correction. Resampling techniques are performed to ensure that the observations are significant and reliable. We focus on two components of interest widely used in analyzing SZs, including the default mode network (DMN) and auditory cortex. Results show that the spatial source phase exhibits more significant variance changes and higher sensitivity to the spatial differences between SZs and HCs in the anterior areas of DMN and the left auditory cortex, compared to the magnitude of spatial activations. Our findings show that the spatial source phase can potentially serve as a new brain imaging biomarker and provide a novel perspective on differences in SZs compared to HCs, consistent with but extending previous work showing increased variability in patient data. [ABSTRACT FROM AUTHOR]

Aim: In this work, we propose the novel use of adaptively constrained independent vector analysis (acIVA) to effectively capture the temporal and spatial properties of dynamic blood-oxygen-level-dependent (BOLD) activity (dBA), and we efficiently quantify the spatial property of dBA (sdBA). We also propose to incorporate dBA into the study of brain dynamics to gain insight into activity-connectivity co-evolution patterns. Introduction: Studies of the dynamics of the human brain using functional magnetic resonance imaging (fMRI) have enabled the identification of unique functional network connectivity (FNC) states and provided new insights into mental disorders. There is evidence showing that both BOLD activity, which is captured by fMRI, and FNC are related to mental and cognitive processes. However, a few studies have evaluated the inter-relationships of these two domains of function. Moreover, the identification of subgroups of schizophrenia has gained significant clinical importance due to a need to study the heterogeneity of schizophrenia. Methods: We design a simulation study to verify the effectiveness of acIVA and apply acIVA to the dynamic study of resting-state fMRI data collected from individuals with schizophrenia and healthy controls (HCs) to investigate the relationship between dBA and dynamic FNC (dFNC). Results: The simulation study demonstrates that acIVA accurately captures the spatial variability and provides an efficient quantification of sdBA. The fMRI analysis yields synchronized sdBA-temporal property of dBA (tdBA) patterns and shows that the dBA and dFNC are significantly correlated in the spatial domain. Using these dynamic features, we identify schizophrenia subgroups with significant differences in terms of their clinical symptoms. Conclusion: We find that brain function is abnormally organized in schizophrenia compared with HCs since there are less synchronized sdBA-tdBA patterns in schizophrenia and schizophrenia prefers a component that merges multiple brain regions. Identification of schizophrenia subgroups using dynamic features inspires the use of neuroimaging in studying the heterogeneity of disorders. Impact statement This work introduces the use of joint blind source separation for the study of brain dynamics to enable efficient quantification of the spatial property of dynamic blood-oxygen-level-dependent (BOLD) activity to provide insight into the relationship of dynamic BOLD activity and dynamic functional network connectivity. The identification of subgroups of schizophrenia using dynamic features allows the study of heterogeneity of schizophrenia, emphasizing the importance of functional magnetic resonance imaging analysis in the study of brain activity and functional connectivity to gain a better understanding of the human brain, especially the brain with a mental disorder.