Pre-training techniques based on functional connectivity (FC) have demonstrated great potential in brain disease diagnosis. However, previous studies may disrupt the functional information of training data when designing pre-training tasks, and may be limited by biases stemming from single-task learning or insufficient coordination among multiple task components, thereby hindering the acquisition of robust and generalizable feature representations. To address these limitations, we proposed a novel pre-training framework, named Multi-view Contrastive and Masked ROI Learning (CoMa), to learn general representations from healthy datasets through improved learning tasks, with flexible domain-adaptive fine-tuning for downstream tasks. Results showed that the proposed CoMa achieved superior performance across a broad spectrum of diagnostic tasks, significantly outperforming the alternative methods, emphasizing its generalization and effectiveness. Furthermore, the model can further enhance the diagnostic accuracy through task-specific fine-tuning within particular disease domains, indicating its potential for adaptive disease diagnosis. Additionally, we also identified interpretable diagnostic biomarkers for childhood developmental disorders, psychiatric disorders, and neurodegenerative disorders. Overall, the proposed CoMa is instrumental toward the application of fundamental model for disease diagnosis and improves our understanding of underlying mechanisms of common brain disorders.

The cross-modal synthesis between structural magnetic resonance imaging (sMRI) and functional network connectivity (FNC) is a relatively unexplored area in medical imaging, especially with respect to schizophrenia. This study employs conditional Vision Transformer Generative Adversarial Networks (cViT-GANs) to generate FNC data based on sMRI inputs. After training on a comprehensive dataset that included both individuals with schizophrenia and healthy control subjects, our cViT-GAN model effectively synthesized the FNC matrix for each subject, and then formed a group difference FNC matrix, obtaining a Pearson correlation of 0.73 with the actual FNC matrix. In addition, our FNC visualization results demonstrate significant correlations in particular subcortical brain regions, highlighting the model’s capability of capturing detailed structural-functional associations. This performance distinguishes our model from conditional CNN-based GAN alternatives such as Pix2Pix. Our research is one of the first attempts to link sMRI and FNC synthesis, setting it apart from other cross-modal studies that concentrate on T1- and T2-weighted MR images or the fusion of MRI and CT scans.

Neurocognitive impairment continues to be common comorbidity for people living with HIV (PLWH). Given the chronic nature of HIV disease, identifying reliable biomarkers of these impairments is essential to advance our understanding of the underlying neural foundation and facilitate screening and diagnosis in clinical care. While neuroimaging provides immense potential for such biomarkers, to date, investigations in PLWH have been mostly limited to either univariate mass techniques or a single neuroimaging modality. In the present study, connectome-based predictive modeling (CPM) was proposed to predict individual differences of cognitive functioning in PLWH, using resting-state functional connectivity (FC), white matter structural connectivity (SC), and clinical relevant measures. We also adopted an efficient feature selection approach to identify the most predictive features, which achieved an optimal prediction accuracy of r = 0.61 in the discovery dataset (n = 102) and r = 0.45 in an independent validation HIV cohort (n = 88). Two brain templates and nine distinct prediction models were also tested for better modeling generalizability. Results show that combining multimodal FC and SC features enabled higher prediction accuracy of cognitive scores in PLWH, while adding clinical and demographic metrics may further improve the prediction by introducing complementary information, which may help better evaluate the individual-level cognitive performance in PLWH.

Convolutional neural networks (CNNs) have shown promising results in classifying individuals with mental disorders such as schizophrenia using resting-state fMRI data. However, complex-valued fMRI data is rarely used since additional phase data introduces high-level noise though it is potentially useful information for the context of classification. As such, we propose to use spatial source phase (SSP) maps derived from complex-valued fMRI data as the CNN input. The SSP maps are not only less noisy, but also more sensitive to spatial activation changes caused by mental disorders than magnitude maps. We build a 3D-CNN framework with two convolutional layers (named SSPNet) to fully explore the 3D structure and voxel-level relationships from the SSP maps. Two interpretability modules, consisting of saliency map generation and gradient-weighted class activation mapping (Grad-CAM), are incorporated into the well-trained SSPNet to provide additional information helpful for understanding the output. Experimental results from classifying schizophrenia patients (SZs) and healthy controls (HCs) show that the proposed SSPNet significantly improved accuracy and AUC compared to CNN using magnitude maps extracted from either magnitude-only (by 23.4 and 23.6% for DMN) or complex-valued fMRI data (by 10.6 and 5.8% for DMN). SSPNet captured more prominent HC-SZ differences in saliency maps, and Grad-CAM localized all contributing brain regions with opposite strengths for HCs and SZs within SSP maps. These results indicate the potential of SSPNet as a sensitive tool that may be useful for the development of brain-based biomarkers of mental disorders.

Convolutional neural network (CNN) can achieve better classification by using independent component analysis (ICA) components derived from complex-valued fMRI data than from magnitude-only fMRI data due to incorporating additional phase information. However, thus far magnitude slices of only a single brain network (i.e. spatial component) has been used in the classification. This study aims to take advantages of multiple ICA components in providing rich information and to provide a conclusion for efficient multiple-component fusion. More precisely, we present three fusion approaches: 1) averaging multiple ICA components as inputs of a single-component CNN, 2) concatenating features of multiple single-component CNN, and 3) averaging predictive probabilities of multiple single-component CNN. We evaluate the proposed methods using resting-state fMRI data collected from 42 schizophrenia patients and 40 healthy controls. Experimental results show that all three fusion approaches can improve classification accuracy compared to the single-component CNN, and the first approach performs the best. No matter which fusion method is used, we reach the same conclusion that four-component fusion is sufficient to obtain satisfying performance, and two-component fusion yields higher improvement and better performance than the single-component classification, especially when using components having good accuracy for single-component CNN classification.

Brain connectivity alterations associated with mental disorders have been widely reported in both functional MRI (fMRI) and diffusion MRI (dMRI). However, extracting useful information from the vast amount of information afforded by brain networks remains a great challenge. Capturing network topology, graph convolutional networks (GCNs) have demonstrated to be superior in learning network representations tailored for identifying specific brain disorders. Existing graph construction techniques generally rely on a specific brain parcellation to define regions-of-interest (ROIs) to construct networks, often limiting the analysis into a single spatial scale. In addition, most methods focus on the pairwise relationships between the ROIs and ignore high-order associations between subjects. In this letter, we propose a mutual multi-scale triplet graph convolutional network (MMTGCN) to analyze functional and structural connectivity for brain disorder diagnosis. We first employ several templates with different scales of ROI parcellation to construct coarse-to-fine brain connectivity networks for each subject. Then, a triplet GCN (TGCN) module is developed to learn functional/structural representations of brain connectivity networks at each scale, with the triplet relationship among subjects explicitly incorporated into the learning process. Finally, we propose a template mutual learning strategy to train different scale TGCNs collaboratively for disease classification. Experimental results on 1,160 subjects from three datasets with fMRI or dMRI data demonstrate that our MMTGCN outperforms several state-of-the-art methods in identifying three types of brain disorders.

Human brain connectivity is complex. Graph theory based analysis has become a powerful and popular approach for analyzing brain imaging data, largely because of its potential to quantitatively illuminate the networks, the static architecture in structure and function, the organization of dynamic behavior over time, and disease related brain changes. The first step in creating brain graphs is to define the nodes and edges connecting them. We review a number of approaches for defining brain nodes including fixed versus data-driven nodes. Expanding the narrow view of most studies which focus on static and/or single modality brain connectivity, we also survey advanced approaches and their performances in building dynamic and multi-modal brain graphs. We show results from both simulated and real data from healthy controls and patients with mental illnesse. We outline the advantages and challenges of these various techniques. By summarizing and inspecting recent studies which analyzed brain imaging data based on graph theory, this article provides a guide for developing new powerful tools to explore complex brain networks.

By exploiting cross-information among multiple imaging data, multimodal fusion has often been used to better understand brain diseases. However, most current fusion approaches are blind, without adopting any prior information. There is increasing interest to uncover the neurocognitive mapping of specific clinical measurements on enriched brain imaging data; hence, a supervised, goal-directed model that employs prior information as a reference to guide multimodal data fusion is much needed and becomes a natural option. Here, we proposed a fusion with reference model called "multi-site canonical correlation analysis with reference + joint-independent component analysis" (MCCAR+jICA), which can precisely identify co-varying multimodal imaging patterns closely related to the reference, such as cognitive scores. In a three-way fusion simulation, the proposed method was compared with its alternatives on multiple facets; MCCAR+jICA outperforms others with higher estimation precision and high accuracy on identifying a target component with the right correspondence. In human imaging data, working memory performance was utilized as a reference to investigate the co-varying working memory-associated brain patterns among three modalities and how they are impaired in schizophrenia. Two independent cohorts (294 and 83 subjects respectively) were used. Similar brain maps were identified between the two cohorts along with substantial overlaps in the central executive network in fMRI, salience network in sMRI, and major white matter tracts in dMRI. These regions have been linked with working memory deficits in schizophrenia in multiple reports and MCCAR+jICA further verified them in a repeatable, joint manner, demonstrating the ability of the proposed method to identify potential neuromarkers for mental disorders.

Independent component analysis (ICA) is a statistical and computational technique for revealing hidden factors that underlie sets of signals. We propose an improved ICA framework for group data analysis by adding an adaptive constraint to the mixing coefficients, namely, constrained coefficients ICA (CCICA). The method is dedicated to identification and increasing the accuracy of components that show significant group differences reflected in the mixing coefficients. Performance of CCICA is assessed by simulations under different signal to noise ratios. An application to multitask functional magnetic resonance imaging analysis is conducted to illustrate the advantages of CCICA. It is shown that CCICA provides stable results and can estimate both the components and the mixing coefficients with a relatively high accuracy compared to Infomax, hence is a promising tool for the identification of biomarkers from brain imaging data.