Exploring General Intelligence via Gated Graph Transformer in Functional Connectivity Studies.

Functional connectivity (FC) as derived from fMRI has emerged as a pivotal tool in elucidating the intricacies of various psychiatric disorders and delineating the neural pathways that underpin cognitive and behavioral dynamics inherent to the human brain. While Graph Neural Networks (GNNs) offer a structured approach to represent neuroimaging data, they are limited by their need for a predefined graph structure to depict associations between brain regions, a detail not solely provided by FCs. To bridge this gap, we introduce the Gated Graph Transformer (GGT) framework, designed to predict cognitive metrics based on FCs. Empirical validation on the Philadelphia Neurodevelopmental Cohort (PNC) underscores the superior predictive prowess of our model, further accentuating its potential in identifying pivotal neural connectivities that correlate with human cognitive processes.

Interpretable Cognitive Ability Prediction: A Comprehensive Gated Graph Transformer Framework for Analyzing Functional Brain Networks.

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.

Latent Similarity Identifies Important Functional Connections for Phenotype Prediction.

OBJECTIVE: Endophenotypes such as brain age and fluid intelligence are important biomarkers of disease status. However, brain imaging studies to identify these biomarkers often encounter limited numbers of subjects but high dimensional imaging features, hindering reproducibility. Therefore, we develop an interpretable, multivariate classification/regression algorithm, called Latent Similarity (LatSim), suitable for small sample size but high feature dimension datasets. METHODS: LatSim combines metric learning with a kernel similarity function and softmax aggregation to identify task-related similarities between subjects. Inter-subject similarity is utilized to improve performance on three prediction tasks using multi-paradigm fMRI data. A greedy selection algorithm, made possible by LatSim's computational efficiency, is developed as an interpretability method. RESULTS: LatSim achieved significantly higher predictive accuracy at small sample sizes on the Philadelphia Neurodevelopmental Cohort (PNC) dataset. Connections identified by LatSim gave superior discriminative power compared to those identified by other methods. We identified 4 functional brain networks enriched in connections for predicting brain age, sex, and intelligence. CONCLUSION: We find that most information for a predictive task comes from only a few (1-5) connections. Additionally, we find that the default mode network is over-represented in the top connections of all predictive tasks. SIGNIFICANCE: We propose a novel prediction algorithm for small sample, high feature dimension datasets and use it to identify connections in task fMRI data. Our work can lead to new insights in both algorithm design and neuroscience research.

Detecting abnormal connectivity in schizophrenia via a joint directed acyclic graph estimation model.

Functional connectivity (FC) between brain region has been widely studied and linked with cognition and behavior of an individual. FC is usually defined as the correlation or partial correlation of fMRI blood oxygen level-dependent (BOLD) signals between two brain regions. Although FC has been effective to understand brain organization, it cannot reveal the direction of interactions. Many directed acyclic graph (DAG) based methods have been applied to study the directed interactions but their performance was limited by the small sample size while high dimensionality of the available data. By enforcing group regularization and utilizing samples from both case and control groups, we propose a joint DAG model to estimate the directed FC. We first demonstrate that the proposed model is efficient and accurate through a series of simulation studies. We then apply it to the case-control study of schizophrenia (SZ) with data collected from the MIND Clinical Imaging Consortium (MCIC). We have successfully identified decreased functional integration, disrupted hub structures and characteristic edges (CtEs) in SZ patients. Those findings have been confirmed by previous studies with some identified to be potential markers for SZ patients. A comparison of the results between the directed FC and undirected FC showed substantial differences in the selected features. In addition, we used the identified features based on directed FC for the classification of SZ patients and achieved better accuracy than using undirected FC or raw features, demonstrating the advantage of using directed FC for brain network analysis.

Distance Correlation-Based Brain Functional Connectivity Estimation and Non-Convex Multi-Task Learning for Developmental fMRI Studies.

OBJECTIVE: Resting-state functional magnetic resonance imaging (rs-fMRI)-derived functional connectivity (FC) patterns have been extensively used to delineate global functional organization of the human brain in healthy development and neuropsychiatric disorders. In this paper, we investigate how FC in males and females differs in an age prediction framework. METHODS: We first estimate FC between regions-of-interest (ROIs) using distance correlation instead of Pearson's correlation. Distance correlation, as a multivariate statistical method, explores spatial relations of voxel-wise time courses within individual ROIs and measures both linear and nonlinear dependence, capturing more complex between-ROI interactions. Then, we propose a novel non-convex multi-task learning (NC-MTL) model to study age-related gender differences in FC, where age prediction for each gender group is viewed as one task, and a composite regularizer with a combination of the non-convex l2,1-2 and l1-2 terms is introduced for selecting both common and task-specific features. RESULTS AND CONCLUSION: We validate the effectiveness of our NC-MTL model with distance correlation-based FC derived from rs-fMRI for predicting ages of both genders. The experimental results on the Philadelphia Neurodevelopmental Cohort demonstrate that our NC-MTL model outperforms several other competing MTL models in age prediction. We also compare the age prediction performance of our NC-MTL model using FC estimated by Pearson's correlation and distance correlation, which shows that distance correlation-based FC is more discriminative for age prediction than Pearson's correlation-based FC. SIGNIFICANCE: This paper presents a novel framework for functional connectome developmental studies, characterizing developmental gender differences in FC patterns.

Functional connectomes incorporating phase synchronization for the characterization and prediction of individual differences.

BACKGROUND: Functional connectomes have been proven to be able to predict an individual's traits, acting as a fingerprint. A majority of studies use the amplitude information of fMRI signals to construct the connectivity but it remains unknown whether phase synchronization can be incorporated for improved prediction of individual cognitive behaviors. METHODS: In this paper, we address the issue by extracting phase information from the fMRI time series with a phase locking approach, followed by the construction of functional connectomes. RESULTS: We first examine the identification and prediction performance using phase-based profiles in comparison with amplitude-based connectomes. We then combine both phase-based and amplitude-based connectivity to extract subject-specific information enabled by the phase synchronization. Results show that high individual identification rates (from 82.7% to 92.6%) can be achieved by phase-based connectomes. Phase-based connectivity offers unique information complementary to amplitude-based signals. Intra-network phase-locking appears more informative for individual prediction. In addition, phase synchronization can be used to predict cognitive behaviors. COMPARISON WITH EXISTING METHOD: The amplitude-based connectivity cannot capture the subject-specific information due to neural synchronization. The comparison with other phase-based methods has been involved in the discussion session. CONCLUSIONS: Our findings suggest that neural synchronization carries subject-specific information, which can be captured by phase locking value. The incorporation of phase information into connectomes presents a promising approach to understand each individual brain's uniqueness.

Functional connectome fingerprinting: Identifying individuals and predicting cognitive functions via autoencoder.

Functional network connectivity has been widely acknowledged to characterize brain functions, which can be regarded as "brain fingerprinting" to identify an individual from a pool of subjects. Both common and unique information has been shown to exist in the connectomes across individuals. However, very little is known about whether and how this information can be used to predict the individual variability of the brain. In this paper, we propose to enhance the uniqueness of individual connectome based on an autoencoder network. Specifically, we hypothesize that the common neural activities shared across individuals may reduce the individual identification. By removing contributions from shared activities, inter-subject variability can be enhanced. Our experimental results on HCP data show that the refined connectomes obtained by utilizing autoencoder with sparse dictionary learning can distinguish an individual from the remaining participants with high accuracy (up to 99.5% for the rest-rest pair). Furthermore, high-level cognitive behaviors (e.g., fluid intelligence, executive function, and language comprehension) can also be better predicted with the obtained refined connectomes. We also find that high-order association cortices contribute more to both individual discrimination and behavior prediction. In summary, our proposed framework provides a promising way to leverage functional connectivity networks for cognition and behavior study, in addition to a better understanding of brain functions.

Interpretable Multimodal Fusion Networks Reveal Mechanisms of Brain Cognition.

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.

Multi-Paradigm fMRI Fusion via Sparse Tensor Decomposition in Brain Functional Connectivity Study.

Functional magnetic resonance imaging (fMRI) is a powerful technique with the potential to estimate individual variations in behavioral and cognitive traits. Joint learning of multiple datasets can utilize their complementary information so as to improve learning performance, but it also gives rise to the challenge for data fusion to effectively integrate brain patterns elicited by multiple fMRI data. However, most of the current data fusion methods analyze each single dataset separately and further infer the relationship among them, which fail to utilize the multidimensional structure inherent across modalities and may ignore complex but important interactions. To address this issue, we propose a novel sparse tensor decomposition method to integrate multiple task-stimulus (paradigm) fMRI data. Seeing each paradigm fMRI as one modality, our proposed method considers the relationships across subjects and modalities simultaneously. In specific, a third-order tensor is first modeled by using the functional network connectivity (FNC) of subjects in multiple fMRI paradigms. A novel sparse tensor decomposition with the regularization terms is designed to factorize the tensor into a series of rank-one components, which can extract the shared components across modalities as the embedded features. The L2,1-norm regularizer (i.e., group sparsity) is enforced to select a few common features among multiple subjects. Validation of the proposed method is performed on realistic three paradigm fMRI datasets from the Philadelphia Neurodevelopmental Cohort (PNC) study, for the study of the relationship between the FNC and human cognitive abilities. Experimental results show our method outperforms several other competing methods in the prediction of individuals with different cognitive behaviors via the wide range achievement test (WRAT). Furthermore, our method discovers the FNC related to the cognitive behaviors, such as the connectivity associated with the default mode network (DMN) for three paradigms, and the connectivity between DMN and visual (VIS) domains within the emotion task.

Prediction and classification of sleep quality based on phase synchronization related whole-brain dynamic connectivity using resting state fMRI.

Recently, functional network connectivity (FNC) has been extended from static to dynamic analysis to explore the time-varying functional organization of brain networks. Nowadays, a majority of dynamic FNC (dFNC) analysis frameworks identified recurring FNC patterns with linear correlations based on the amplitude of fMRI time series. However, the brain is a complex dynamical system and phase synchronization provides more informative measures. This paper proposes a novel framework for the prediction/classification of behaviors and cognitions based on the dFNCs derived from phase locking value. When applying to the analysis of fMRI data from Human Connectome Project (HCP), four dFNC states are identified for the study of sleep quality. State 1 exhibits most intense phase synchronization across the whole brain. States 2 and 3 have low and weak connections, respectively. State 4 exhibits strong phase synchronization in intra and inter-connections of somatomotor, visual and cognitive control networks. Through the two-sample t-test, we reveal that for the group with bad sleep quality, state 4 shows decreased phase synchronization within and between networks such as subcortical, auditory, somatomotor and visual, but increased phase synchronization within cognitive control network, and between this network and somatomotor/visual/default-mode/cerebellar networks. The networks with increased phase synchronization in state 4 behave oppositely in state 2. Group differences are absent in state 3, and weak in state 1. We establish a prediction model by linear regression of FNC against sleep quality, and adopt a support vector machine approach for the classification. We compare the performance between conventional FNC and PLV-based dFNC with cross-validation. Results show that the PLV-based dFNC significantly outperforms the conventional FNC in terms of both predictive power and classification accuracy. We also observe that combining static and dynamic features does not significantly improve the classification over using dFNC features alone. Overall, the proposed approach provides a novel means to assess dFNC, which can be used as brain fingerprints to facilitate prediction and classification.

Causality-Based Feature Fusion for Brain Neuro-Developmental Analysis.

Human brain development is a complex and dynamic process caused by several factors such as genetics, sex hormones, and environmental changes. A number of recent studies on brain development have examined functional connectivity (FC) defined by the temporal correlation between time series of different brain regions. We propose to add the directional flow of information during brain maturation. To do so, we extract effective connectivity (EC) through Granger causality (GC) for two different groups of subjects, i.e., children and young adults. The motivation is that the inclusion of causal interaction may further discriminate brain connections between two age groups and help to discover new connections between brain regions. The contributions of this study are threefold. First, there has been a lack of attention to EC-based feature extraction in the context of brain development. To this end, we propose a new kernel-based GC (KGC) method to learn nonlinearity of complex brain network, where a reduced Sine hyperbolic polynomial (RSP) neural network was used as our proposed learner. Second, we used causality values as the weight for the directional connectivity between brain regions. Our findings indicated that the strength of connections was significantly higher in young adults relative to children. In addition, our new EC-based feature outperformed FC-based analysis from Philadelphia neurocohort (PNC) study with better discrimination of different age groups. Moreover, the fusion of these two sets of features (FC + EC) improved brain age prediction accuracy by more than 4%, indicating that they should be used together for brain development studies.

Estimating Dynamic Functional Brain Connectivity With a Sparse Hidden Markov Model.

Estimating dynamic functional network connectivity (dFNC) of the brain from functional magnetic resonance imaging (fMRI) data can reveal both spatial and temporal organization and can be applied to track the developmental trajectory of brain maturity as well as to study mental illness. Resting state fMRI (rs-fMRI) is regarded as a promising task since it reflects the spontaneous brain activity without an external stimulus. The sliding window method has been successfully used to extract dFNC but typically assumes a fixed window size. The hidden Markov model (HMM) based method is an alternative approach for estimating time-varying connectivity. In this paper, we propose a sparse HMM based on Gaussian HMM and Gaussian graphical model (GGM). In this model, the time-varying neural processes are represented as discrete brain states which are described with functional connectivity networks. By enforcing the sparsity on the precision matrix, we can get interpretable connectivity between different functional regions. The optimization of our model can be realized with the expectation maximization (EM) and graphical least absolute shrinkage and selection operator (glasso) algorithms. The proposed model is validated on both simulated blood oxygenation-level dependent (BOLD) time series and rs-fMRI data. Results indicate that the proposed model can capture both stationary and abrupt brain activity fluctuations. We also compare dFNC patterns between children and young adults from the Philadelphia Neurodevelopmental Cohort (PNC) study. Both spatial and temporal behavior of the dFNC are analyzed and compared. The results provide insight into the developmental trajectory across childhood and motivate further research on brain connectivity.

A GICA-TVGL framework to study sex differences in resting state fMRI dynamic connectivity.

BACKGROUND: Functional magnetic resonance imaging (fMRI) has been implemented widely to study brain connectivity. In particular, time-varying connectivity analysis has emerged as an important measure to uncover essential knowledge within the network. On the other hand, independent component analysis (ICA) has served as a powerful tool to preprocess fMRI data before performing network analysis. Together, they may lead to novel findings. METHODS: We propose a new framework (GICA-TVGL) that combines group ICA (GICA) with time-varying graphical LASSO (TVGL) to improve the power of analyzing functional connectivity (FNC) changes, which is then applied for neuro-developmental study. To investigate the performance of our proposed approach, we apply it to capture dynamic FNC using both the Philadelphia Neurodevelopmental Cohort (PNC) and the Pediatric Imaging, Neurocognition, and Genetics (PING) datasets. RESULTS: Our results indicate that females and males in young adult group possess substantial difference related to visual network. In addition, some other consistent conclusions have been reached by using these two datasets. Furthermore, the GICA-TVGL model indicated that females had a higher probability to stay in a stable state. Males had a higher tendency to remain in a globally disconnected mode. COMPARISON WITH EXISTING METHOD: The performance of sliding window approach is largely affected by the window size selection. In addition, it also assumes temporal locality hypothesis. CONCLUSION: Our proposed framework provides a feasible method to investigate brain dynamics and has the potential to become a widely used tool in neuroimaging studies.

Refined measure of functional connectomes for improved identifiability and prediction.

Brain functional connectome analysis is commonly based on population-wise inference. However, in this way precious information provided at the individual subject level may be overlooked. Recently, several studies have shown that individual differences contribute strongly to the functional connectivity patterns. In particular, functional connectomes have been proven to offer a fingerprint measure, which can reliably identify a given individual from a pool of participants. In this work, we propose to refine the standard measure of individual functional connectomes using dictionary learning. More specifically, we rely on the assumption that each functional connectivity is dominated by stable group and individual factors. By subtracting population-wise contributions from connectivity patterns facilitated by dictionary representation, intersubject variability should be increased within the group. We validate our approach using several types of analyses. For example, we observe that refined connectivity profiles significantly increase subject-specific identifiability across functional magnetic resonance imaging (fMRI) session combinations. Besides, refined connectomes can also improve the prediction power for cognitive behaviors. In accordance with results from the literature, we find that individual distinctiveness is closely linked with differences in neurocognitive activity within the brain. In summary, our results indicate that individual connectivity analysis benefits from the group-wise inferences and refined connectomes are indeed desirable for brain mapping.

Capturing Dynamic Connectivity from Resting State fMRI using Time-Varying Graphical Lasso.

Functional connectivity (FC) within the human brain evaluated through functional magnetic resonance imaging (fMRI) data has attracted increasing attention and has been employed to study the development of the brain or health conditions of the brain. Many different approaches have been proposed to estimate FC from fMRI data, whereas many of them rely on an implicit assumption that functional connectivity should be static throughout the fMRI scan session. Recently, the fMRI community has realized the limitation of assuming static connectivity and dynamic approaches are more prominent in the resting state fMRI (rs-fMRI) analysis. The sliding window technique has been widely used in many studies to capture network dynamics, but has a number of limitations. In this study, we apply a time-varying graphical lasso (TVGL) model, an extension from the traditional graphical lasso, to address the challenge, which can greatly improve the estimation of FC. The performance of estimating dynamic FC is evaluated with the TVGL through both simulated experiments and real rs-fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC) project. Improved performance is achieved over the sliding window technique. In particular, group differences and transition behaviours between young adults and children are investigated using the estimated dynamic connectivity networks, which help us to better unveil the mechanisms underlying the evolution of the brain over time.