The combination of multimodal imaging and genomics provides a more comprehensive way for the study of mental illnesses and brain functions. Deep network-based data fusion models have been developed to capture their complex associations, resulting in improved diagnosis of diseases. However, deep learning models are often difficult to interpret, bringing about challenges for uncovering biological mechanisms using these models. In this work, we develop an interpretable multimodal fusion model to perform automated diagnosis and result interpretation simultaneously. We name it Grad-CAM guided convolutional collaborative learning (gCAM-CCL), which is achieved by combining intermediate feature maps with gradient-based weights. The gCAM-CCL model can generate interpretable activation maps to quantify pixel-level contributions of the input features. Moreover, the estimated activation maps are class-specific, which can therefore facilitate the identification of biomarkers underlying different groups. We validate the gCAM-CCL model on a brain imaging-genetic study, and demonstrate its applications to both the classification of cognitive function groups and the discovery of underlying biological mechanisms. Specifically, our analysis results suggest that during task-fMRI scans, several object recognition related regions of interests (ROIs) are activated followed by several downstream encoding ROIs. In addition, the high cognitive group may have stronger neurotransmission signaling while the low cognitive group may have problems in brain/neuron development due to genetic variations.

Objective: Multi-modal functional magnetic resonance imaging (fMRI) can be used to make predictions about individual behavioral and cognitive traits based on brain connectivity networks. Methods: To take advantage of complementary information from multi-modal fMRI, we propose an interpretable multi-modal graph convolutional network (MGCN) model, incorporating both fMRI time series and functional connectivity (FC) between each pair of brain regions. Specifically, our model learns a graph embedding from individual brain networks derived from multi-modal data. A manifold-based regularization term is enforced to consider the relationships of subjects both within and between modalities. Furthermore, we propose the gradient-weighted regression activation mapping (Grad-RAM) and the edge mask learning to interpret the model, which is then used to identify significant cognition-related biomarkers. Results: We validate our MGCN model on the Philadelphia Neurodevelopmental Cohort to predict individual wide range achievement test (WRAT) score. Our model obtains superior predictive performance over GCN with a single modality and other competing approaches. The identified biomarkers are cross-validated from different approaches. Conclusion and Significance: This paper develops a new interpretable graph deep learning framework for cognition prediction, with the potential to overcome the limitations of several current data-fusion models. The results demonstrate the power of MGCN in analyzing multi-modal fMRI and discovering significant biomarkers for human brain studies.

Multimodal neuroimaging data modeling has become a widely used approach but confronts considerable challenges due to their heterogeneity, which encompasses variability in data types, scales, and formats across modalities. This variability necessitates the deployment of advanced computational methods to integrate and interpret diverse datasets within a cohesive analytical framework. In our research, we combine functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), and structural MRI (sMRI) for joint analysis. This integration capitalizes on the unique strengths of each modality and their inherent interconnections, aiming for a comprehensive understanding of the brain's connectivity and anatomical characteristics. Utilizing the Glasser atlas for parcellation, we integrate imaging-derived features from multiple modalities - functional connectivity from fMRI, structural connectivity from DTI, and anatomical features from sMRI - within consistent regions. Our approach incorporates a masking strategy to differentially weight neural connections, thereby facilitating an amalgamation of multimodal imaging data. This technique enhances interpretability at the connectivity level, transcending traditional analyses centered on singular regional attributes. The model is applied to the Human Connectome Project's Development study to elucidate the associations between multimodal imaging and cognitive functions throughout youth. The analysis demonstrates improved prediction accuracy and uncovers crucial anatomical features and neural connections, deepening our understanding of brain structure and function. This study not only advances multimodal neuroimaging analytics by offering a novel method for integrative analysis of diverse imaging modalities but also improves the understanding of intricate relationships between brain's structural and functional networks and cognitive development.

Objective: Graphical deep learning models provide a desirable way for brain functional connectivity analysis. However, the application of current graph deep learning models to brain network analysis is challenging due to the limited sample size and complex relationships between different brain regions. Method: In this work, a graph convolutional network (GCN) based framework is proposed by exploiting the information from both region-to-region connectivities of the brain and subject-subject relationships. We first construct an affinity subject-subject graph followed by GCN analysis. A Laplacian regularization term is introduced in our model to tackle the overfitting problem. We apply and validate the proposed model to the Philadelphia Neurodevelopmental Cohort for the brain cognition study. Results: Experimental analysis shows that our proposed framework outperforms other competing models in classifying groups with low and high Wide Range Achievement Test (WRAT) scores. Moreover, to examine each brain region’s contribution to cognitive function, we use the occlusion sensitivity analysis method to identify cognition-related brain functional networks. The results are consistent with previous research yet yield new findings. Conclusion and significance: Our study demonstrates that GCN incorporating prior knowledge about brain networks offers a powerful way to detect important brain networks and regions associated with cognitive functions.

Graph convolutional deep learning has emerged as a promising method to explore the functional organization of the human brain in neuroscience research. This paper presents a novel framework that utilizes the gated graph transformer (GGT) model to predict individuals’ cognitive ability based on functional connectivity (FC) derived from fMRI. Our framework incorporates prior spatial knowledge and uses a random-walk diffusion strategy that captures the intricate structural and functional relationships between different brain regions. Specifically, our approach employs learnable structural and positional encodings (LSPE) in conjunction with a gating mechanism to efficiently disentangle the learning of positional encoding (PE) and graph embeddings. Additionally, we utilize the attention mechanism to derive multi-view node feature embeddings and dynamically distribute propagation weights between each node and its neighbors, which facilitates the identification of significant biomarkers from functional brain networks and thus enhances the interpretability of the findings. To evaluate our proposed model in cognitive ability prediction, we conduct experiments on two large-scale brain imaging datasets: the Philadelphia Neurodevelopmental Cohort (PNC) and the Human Connectome Project (HCP). The results show that our approach not only outperforms existing methods in prediction accuracy but also provides superior explainability, which can be used to identify important FCs underlying cognitive behaviors.