U-shaped convolutional transformer GAN with multi-resolution consistency loss for restoring brain functional time-series and dementia diagnosis.

Introduction: The blood oxygen level-dependent (BOLD) signal derived from functional neuroimaging is commonly used in brain network analysis and dementia diagnosis. Missing the BOLD signal may lead to bad performance and misinterpretation of findings when analyzing neurological disease. Few studies have focused on the restoration of brain functional time-series data. Methods: In this paper, a novel U-shaped convolutional transformer GAN (UCT-GAN) model is proposed to restore the missing brain functional time-series data. The proposed model leverages the power of generative adversarial networks (GANs) while incorporating a U-shaped architecture to effectively capture hierarchical features in the restoration process. Besides, the multi-level temporal-correlated attention and the convolutional sampling in the transformer-based generator are devised to capture the global and local temporal features for the missing time series and associate their long-range relationship with the other brain regions. Furthermore, by introducing multi-resolution consistency loss, the proposed model can promote the learning of diverse temporal patterns and maintain consistency across different temporal resolutions, thus effectively restoring complex brain functional dynamics. Results: We theoretically tested our model on the public Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and our experiments demonstrate that the proposed model outperforms existing methods in terms of both quantitative metrics and qualitative assessments. The model's ability to preserve the underlying topological structure of the brain functional networks during restoration is a particularly notable achievement. Conclusion: Overall, the proposed model offers a promising solution for restoring brain functional time-series and contributes to the advancement of neuroscience research by providing enhanced tools for disease analysis and interpretation.

Prior-Guided Adversarial Learning With Hypergraph for Predicting Abnormal Connections in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by alterations of the brain's structural and functional connectivity during its progressive degenerative processes. Existing auxiliary diagnostic methods have accomplished the classification task, but few of them can accurately evaluate the changing characteristics of brain connectivity. In this work, a prior-guided adversarial learning with hypergraph (PALH) model is proposed to predict abnormal brain connections using triple-modality medical images. Concretely, a prior distribution from anatomical knowledge is estimated to guide multimodal representation learning using an adversarial strategy. Also, the pairwise collaborative discriminator structure is further utilized to narrow the difference in representation distribution. Moreover, the hypergraph perceptual network is developed to effectively fuse the learned representations while establishing high-order relations within and between multimodal images. Experimental results demonstrate that the proposed model outperforms other related methods in analyzing and predicting AD progression. More importantly, the identified abnormal connections are partly consistent with previous neuroscience discoveries. The proposed model can evaluate the characteristics of abnormal brain connections at different stages of AD, which is helpful for cognitive disease study and early treatment.

BDHT: Generative AI Enables Causality Analysis for Mild Cognitive Impairment.

Effective connectivity estimation plays a crucial role in understanding the interactions and information flow between different brain regions. However, the functional time series used for estimating effective connectivity is derived from certain software, which may lead to large computing errors because of different parameter settings and degrade the ability to model complex causal relationships between brain regions. In this paper, a brain diffuser with hierarchical transformer (BDHT) is proposed to estimate effective connectivity for mild cognitive impairment (MCI) analysis. To our best knowledge, the proposed brain diffuser is the first generative model to apply diffusion models to the application of generating and analyzing multimodal brain networks. Specifically, the BDHT leverages structural connectivity to guide the reverse processes in an efficient way. It makes the denoising process more reliable and guarantees effective connectivity estimation accuracy. To improve denoising quality, the hierarchical denoising transformer is designed to learn multi-scale features in topological space. By stacking the multi-head attention and graph convolutional network, the graph convolutional transformer (GraphConformer) module is devised to enhance structure-function complementarity and improve the ability in noise estimation. Experimental evaluations of the denoising diffusion model demonstrate its effectiveness in estimating effective connectivity. The proposed model achieves superior performance in terms of accuracy and robustness compared to existing approaches. Moreover, the proposed model can identify altered directional connections and provide a comprehensive understanding of parthenogenesis for MCI treatment.

Alzheimer's Disease Prediction via Brain Structural-Functional Deep Fusing Network.

Fusing structural-functional images of the brain has shown great potential to analyze the deterioration of Alzheimer's disease (AD). However, it is a big challenge to effectively fuse the correlated and complementary information from multimodal neuroimages. In this work, a novel model termed cross-modal transformer generative adversarial network (CT-GAN) is proposed to effectively fuse the functional and structural information contained in functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). The CT-GAN can learn topological features and generate multimodal connectivity from multimodal imaging data in an efficient end-to-end manner. Moreover, the swapping bi-attention mechanism is designed to gradually align common features and effectively enhance the complementary features between modalities. By analyzing the generated connectivity features, the proposed model can identify AD-related brain connections. Evaluations on the public ADNI dataset show that the proposed CT-GAN can dramatically improve prediction performance and detect AD-related brain regions effectively. The proposed model also provides new insights into detecting AD-related abnormal neural circuits.

Brain Structure-Function Fusing Representation Learning Using Adversarial Decomposed-VAE for Analyzing MCI.

Integrating the brain structural and functional connectivity features is of great significance in both exploring brain science and analyzing cognitive impairment clinically. However, it remains a challenge to effectively fuse structural and functional features in exploring the complex brain network. In this paper, a novel brain structure-function fusing-representation learning (BSFL) model is proposed to effectively learn fused representation from diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) for mild cognitive impairment (MCI) analysis. Specifically, the decomposition-fusion framework is developed to first decompose the feature space into the union of the uniform and unique spaces for each modality, and then adaptively fuse the decomposed features to learn MCI-related representation. Moreover, a knowledge-aware transformer module is designed to automatically capture local and global connectivity features throughout the brain. Also, a uniform-unique contrastive loss is further devised to make the decomposition more effective and enhance the complementarity of structural and functional features. The extensive experiments demonstrate that the proposed model achieves better performance than other competitive methods in predicting and analyzing MCI. More importantly, the proposed model could be a potential tool for reconstructing unified brain networks and predicting abnormal connections during the degenerative processes in MCI.

Brain Functional Network Generation Using Distribution-Regularized Adversarial Graph Autoencoder with Transformer for Dementia Diagnosis.

The topological connectivity information derived from the brain functional network can bring new insights for diagnosing and analyzing dementia disorders. The brain functional network is suitable to bridge the correlation between abnormal connectivities and dementia disorders. However, it is challenging to access considerable amounts of brain functional network data, which hinders the widespread application of data-driven models in dementia diagnosis. In this study, a novel distribution-regularized adversarial graph auto-Encoder (DAGAE) with transformer is proposed to generate new fake brain functional networks to augment the brain functional network dataset, improving the dementia diagnosis accuracy of data-driven models. Specifically, the label distribution is estimated to regularize the latent space learned by the graph encoder, which can make the learning process stable and the learned representation robust. Also, the transformer generator is devised to map the node representations into node-to-node connections by exploring the long-term dependence of highly-correlated distant brain regions. The typical topological properties and discriminative features can be preserved entirely. Furthermore, the generated brain functional networks improve the prediction performance using different classifiers, which can be applied to analyze other cognitive diseases. Attempts on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset demonstrate that the proposed model can generate good brain functional networks. The classification results show adding generated data can achieve the best accuracy value of 85.33%, sensitivity value of 84.00%, specificity value of 86.67%. The proposed model also achieves superior performance compared with other related augmented models. Overall, the proposed model effectively improves cognitive disease diagnosis by generating diverse brain functional networks.

Constructing brain functional network by Adversarial Temporal-Spatial Aligned Transformer for early AD analysis.

Introduction: The brain functional network can describe the spontaneous activity of nerve cells and reveal the subtle abnormal changes associated with brain disease. It has been widely used for analyzing early Alzheimer's disease (AD) and exploring pathological mechanisms. However, the current methods of constructing functional connectivity networks from functional magnetic resonance imaging (fMRI) heavily depend on the software toolboxes, which may lead to errors in connection strength estimation and bad performance in disease analysis because of many subjective settings. Methods: To solve this problem, in this paper, a novel Adversarial Temporal-Spatial Aligned Transformer (ATAT) model is proposed to automatically map 4D fMRI into functional connectivity network for early AD analysis. By incorporating the volume and location of anatomical brain regions, the region-guided feature learning network can roughly focus on local features for each brain region. Also, the spatial-temporal aligned transformer network is developed to adaptively adjust boundary features of adjacent regions and capture global functional connectivity patterns of distant regions. Furthermore, a multi-channel temporal discriminator is devised to distinguish the joint distributions of the multi-region time series from the generator and the real sample. Results: Experimental results on the Alzheimer's Disease Neuroimaging Initiative (ADNI) proved the effectiveness and superior performance of the proposed model in early AD prediction and progression analysis. Discussion: To verify the reliability of the proposed model, the detected important ROIs are compared with clinical studies and show partial consistency. Furthermore, the most significant altered connectivity reflects the main characteristics associated with AD. Conclusion: Generally, the proposed ATAT provides a new perspective in constructing functional connectivity networks and is able to evaluate the disease-related changing characteristics at different stages for neuroscience exploration and clinical disease analysis.