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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 $\ell _{2,1-2}$ and $\ell _{1-2}$ 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. [ABSTRACT FROM AUTHOR]

Recent studies show that multi-modal data fusion techniques combine information from diverse sources for comprehensive diagnosis and prognosis of complex brain disorder, often resulting in improved accuracy compared to single-modality approaches. However, many existing data fusion methods extract features from homogeneous networs, ignoring heterogeneous structural information among multiple modalities. To this end, we propose a Hypergraph-based Multi-modal data Fusion algorithm, namely HMF. Specifically, we first generate a hypergraph similarity matrix to represent the high-order relationships among subjects, and then enforce the regularization term based upon both the inter- and intra-modality relationships of the subjects. Finally, we apply HMF to integrate imaging and genetics datasets. Validation of the proposed method is performed on both synthetic data and real samples from schizophrenia study. Results show that our algorithm outperforms several competing methods, and reveals significant interactions among risk genes, environmental factors and abnormal brain regions. [ABSTRACT FROM AUTHOR]

Total anomalous pulmonary venous connection (TAPVC) is a rare but mortal congenital heart disease in children and can be repaired by surgical operations. However, some patients may suffer from pulmonary venous obstruction (PVO) after surgery with insufficient blood supply, necessitating special follow-up strategy and treatment. Therefore, it is a clinically important yet challenging problem to predict such patients before surgery. In this paper, we address this issue and propose a computational framework to determine the risk factors for postoperative PVO (PPVO) from computed tomography angiography (CTA) images and build the PPVO risk prediction model. From clinical experiences, such risk factors are likely from the left atrium (LA) and pulmonary vein (PV) of the patient. Thus, 3D models of LA and PV are first reconstructed from low-dose CTA images. Then, a feature pool is built by computing different morphological features from 3D models of LA and PV, and the coupling spatial features of LA and PV. Finally, four risk factors are identified from the feature pool using the machine learning techniques, followed by a risk prediction model. As a result, not only PPVO patients can be effectively predicted but also qualitative risk factors reported in the literature can now be quantified. Finally, the risk prediction model is evaluated on two independent clinical datasets from two hospitals. The model can achieve the AUC values of 0.88 and 0.87 respectively, demonstrating its effectiveness in risk prediction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Magnetic resonance imagings (MRIs) are providing increased access to neuropsychiatric disorders that can be made available for advanced data analysis. However, the single type of data limits the ability of psychiatrists to distinguish the subclasses of this disease. In this paper, we propose an ensemble hybrid features selection method for the neuropsychiatric disorder classification. The method consists of a 3D DenseNet and a XGBoost, which are used to select the image features from structural MRI images and the phenotypic feature from phenotypic records, respectively. The hybrid feature is composed of image features and phenotypic features. The proposed method is validated in the Consortium for Neuropsychiatric Phenomics (CNP) dataset, where samples are classified into one of the four classes (healthy controls (HC), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), and schizophrenia (SD)). Experimental results show that the hybrid feature can improve the performance of classification methods. The best accuracy of binary and multi-class classification can reach 91.22 and 78.62 percent, respectively. We analyze the importance of phenotypic features and image features in different classification tasks. The importance of the structure MRI images is highlighted by incorporating phenotypic features with image features to generate hybrid features. We also visualize the features of three neuropsychiatric disorders and analyze their locations in the brain region. [ABSTRACT FROM AUTHOR]

Tucker decomposition can provide an intuitive summary to understand brain function by decomposing multi-subject fMRI data into a core tensor and multiple factor matrices, and was mostly used to extract functional connectivity patterns across time/subjects using orthogonality constraints. However, these algorithms are unsuitable for extracting common spatial and temporal patterns across subjects due to distinct characteristics such as high-level noise. Motivated by a successful application of Tucker decomposition to image denoising and the intrinsic sparsity of spatial activations in fMRI, we propose a low-rank Tucker-2 model with spatial sparsity constraint to analyze multi-subject fMRI data. More precisely, we propose to impose a sparsity constraint on spatial maps by using an $ \ell _{p} $ norm (${0}< {p}\le {1}$), in addition to adding low-rank constraints on factor matrices via the Frobenius norm. We solve the constrained Tucker-2 model using alternating direction method of multipliers, and propose to update both sparsity and low-rank constrained spatial maps using half quadratic splitting. Moreover, we extract new spatial and temporal features in addition to subject-specific intensities from the core tensor, and use these features to classify multiple subjects. The results from both simulated and experimental fMRI data verify the improvement of the proposed method, compared with four related algorithms including robust Kronecker component analysis, Tucker decomposition with orthogonality constraints, canonical polyadic decomposition, and block term decomposition in extracting common spatial and temporal components across subjects. The spatial and temporal features extracted from the core tensor show promise for characterizing subjects within the same group of patients or healthy controls as well. [ABSTRACT FROM AUTHOR]

Deep learning (DL) has been extremely successful when applied to the analysis of natural images. By contrast, analyzing neuroimaging data presents some unique challenges, including higher dimensionality, smaller sample sizes, multiple heterogeneous modalities, and a limited ground truth. In this article, we discuss DL methods in the context of four diverse and important categories in the neuroimaging field: classification/prediction, dynamic activity/connectivity, multimodal fusion, and interpretation/visualization. We highlight recent progress in each of these categories, discuss the benefits of combining data characteristics and model architectures, and derive guidelines for the use of DL in neuroimaging data. For each category, we also assess promising applications and major challenges to overcome. Finally, we discuss future directions of neuroimaging DL for clinical applications, a topic of great interest, touching on all four categories. [ABSTRACT FROM AUTHOR]

With the development of multi-model neuroimaging technology and gene detection technology, the efforts of integrating multi-model imaging genetics data to explore the virulence factors of schizophrenia (SZ) are still limited. To address this issue, we propose a novel algorithm called group sparse of joint non-negative matrix factorization on orthogonal subspace (GJNMFO). Our algorithm fuses single nucleotide polymorphism (SNP) data, function magnetic resonance imaging (fMRI) data and epigenetic factors (DNA methylation) by projecting three-model data into a common basis matrix and three different coefficient matrices to identify risk genes, epigenetic factors and abnormal brain regions associated with SZ. Specifically, we introduce orthogonal constraints on the basis matrix to discard unimportant features in the row of coefficient matrices. Since imaging genetics data have rich group information, we draw into group sparse on three coefficient matrices to make the extracted features more accurate. Both the simulated and real Mind Clinical Imaging Consortium (MCIC) datasets are performed to validate our approach. Simulation results show that our algorithm works better than other competing methods. Through the experiments of MCIC datasets, GJNMFO reveals a set of risk genes, epigenetic factors and abnormal brain functional regions, which have been verified to be both statistically and biologically significant. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To understand the association between brain networks and behaviors of an individual, most studies build predictive models based on functional connectivity (FC) from a single dataset with linear analysis techniques. Such approaches may fail to capture the nonlinear structure of brain networks and neglect the complementary information contained in FC networks (FCNs) from multiple datasets. To address this challenging issue, we use multiview dimensionality reduction to extract a coherent low-dimensional representation of the FCNs from resting-state and emotion identification task-based functional magnetic resonance imaging (fMRI) datasets. Methods: We propose a scheme based on multiview diffusion map to extract intrinsic features while preserving the underlying geometric structure of high dimensional datasets. This method is robust to noise and small variations in the data. Results: After validation on the Philadelphia Neurodevelopmental Cohort data, the predictive model built from both resting-state and emotion identification task-based fMRI datasets outperforms the one using each individual fMRI dataset. In addition, the proposed model achieves better prediction performance than principal component analysis (PCA) and three other competing data fusion methods. Conclusion: Our framework for combing multiple FCNs in one predictive model exhibits improved prediction performance. Significance: To our knowledge, we demonstrate a first application of multiview diffusion map to successfully fuse different types of fMRI data for predicting fluid intelligence (gF). [ABSTRACT FROM AUTHOR]

Recent advances in imaging genetics make it possible to combine different types of data including medical images like functional magnetic resonance imaging (fMRI) and genetic data like single nucleotide polymorphisms (SNPs) for comprehensive diagnosis of mental disorders. Understanding complex interactions among these heterogeneous data may give rise to a new perspective, while at the same time demand statistical models for their integration. Various graphical models have been proposed for the study of interaction or association networks with continuous, binary, and count data as well as the mixture of them. However, limited efforts have been made for the multinomial case, for instance, SNP data. Our goal is therefore to fill the void by developing a graphical model for the integration of fMRI image and SNP data, which can provide deeper understanding of the unknown neurogenetic mechanism. In this article, we propose a latent Gaussian copula model for mixed data containing multinomial components. We assume that the discrete variable is obtained by discretizing a latent (unobserved) continuous variable and then create a semi-rank based estimator of the graph structure. The simulation results demonstrate that the proposed latent correlation has more steady and accurate performance than several existing methods in detecting graph structure. When applying to a real schizophrenia data consisting of SNP array and fMRI image collected by the Mind Clinical Imaging Consortium (MCIC), the proposed method reveals a set of distinct SNP-brain associations, which are verified to be biologically significant. The proposed model is statistically promising in handling mixed types of data including multinomial components, which can find widespread applications. To promote reproducible research, the R code is available at https://github.com/Aiying0512/LGCM. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Recently, functional magnetic resonance imaging (fMRI)-derived brain functional connectivity (FC) patterns have been used as fingerprints to predict individual differences in phenotypic measures, and cognitive dysfunction associated with brain diseases. In these applications, how to accurately estimate FC patterns is crucial yet technically challenging. Methods: In this article, we propose a correlation guided graph learning (CGGL) method to estimate FC patterns for establishing brain-behavior relationships. Different from the existing graph learning methods which only consider the graph structure across brain regions-of-interest (ROIs), our proposed CGGL takes into account both the temporal correlation of ROIs across time points, and the graph structure across ROIs. The resulting FC patterns reflect substantial inter-individual variations related to the behavioral measure of interest. Results: We validate the effectiveness of our proposed CGGL on the Philadelphia Neurodevelopmental Cohort data for separately predicting three behavioral measures based on resting-state fMRI. Experimental results demonstrate that the proposed CGGL outperforms other competing FC pattern estimation methods. Conclusion: Our method increases the predictive power of the constructed FC patterns when establishing brain-behavior relationships, and gains meaningful insights into relevant biological mechanisms. Significance: The proposed CGGL offers a more powerful, and reliable method to estimate FC patterns, which can be used as fingerprints in many brain network studies. [ABSTRACT FROM AUTHOR]

With the development of neuroimaging techniques, a growing amount of multi-modal brain imaging data are collected, facilitating comprehensive study of the brain. In this paper, we jointly analyzed functional magnetic resonance imaging (fMRI) collected under different paradigms in order to understand cognitive behaviors of an individual. To this end, we proposed a novel multi-view learning algorithm called structure-enforced collaborative regression (SCoRe) to extract co-expressed discriminative brain regions under the guidance of anatomical structure of the brain. An advantage of SCoRe over its predecessor collaborative regression (CoRe) lies in its incorporation of group structures in the brain imaging data, which makes the model biologically more meaningful. Results from real data analysis has confirmed that by incorporating prior knowledge of brain structure, SCoRe can deliver better prediction performance and is less sensitive to hyper-parameters than CoRe. After validation with simulation experiments, we applied SCoRe to fMRI data collected from the Philadelphia Neurodevelopmental Cohort and adopted the scores from the wide range achievement test (WRAT) to evaluate an individual’s cognitive skills. We located 14 relevant brain regions that can efficiently predict WRAT scores and these brain regions were further confirmed by other independent studies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The context-based convolutional neural network (CNN) is one of the most well-known CNNs to improve the performance of semantic segmentation. It has achieved remarkable success in various medical image segmentation tasks. However, extracting rich and useful context information from complex and changeable medical images is a challenge for medical image segmentation. In this study, a novel Multi-Receptive-Field CNN (MRFNet) is proposed to tackle this challenge. MRFNet offers the optimal receptive field for each subnet in the encoder-decoder module (EDM) and generates multi-receptive-field context information at the feature map level. Moreover, MRFNet fuses these multi-feature maps by the concatenation operation. MRFNet is evaluated on 3 public medical image data sets, including SISS, 3DIRCADb, and SPES. Experimental results show that MRFNet achieves the outstanding performance on all 3 data sets, and outperforms other segmentation methods on 3DIRCADb test set without pre-training the model. [ABSTRACT FROM AUTHOR]

Current developments of neuroimaging and genetics promote an integrative and compressive study of schizophrenia. However, it is still difficult to explore how gene mutations are related to brain abnormalities due to the high dimension but low sample size of these data. Conventional approaches reduce the dimension of dataset separately and then calculate the correlation, but ignore the effects of the response variables and the structure of data. To improve the identification of risk genes and abnormal brain regions on schizophrenia, in this paper, we propose a novel method called Independence and Structural sparsity Canonical Correlation Analysis (ISCCA). ISCCA combines independent component analysis (ICA) and Canonical Correlation Analysis (CCA) to reduce the collinear effects, which also incorporate graph structure of the data into the model to improve the accuracy of feature selection. The results from simulation studies demonstrate its higher accuracy in discovering correlations compared with other competing methods. Moreover, applying ISCCA to a real imaging genetics dataset collected by Mind Clinical Imaging Consortium (MCIC), a set of distinct gene-ROI interactions are identified, which are verified to be both statistically and biologically significant. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a complex disease. Single nucleotide polymorphism (SNP), brain activity measured by functional magnetic resonance imaging (fMRI) and DNA methylation are all important biomarkers that can be used for the study of SZ. To our knowledge, there has been little effort to combine these three datasets together. In this study, we propose a group sparse joint nonnegative matrix factorization (GSJNMF) model to integrate SNP, fMRI, and DNA methylation for the identification of multi-dimensional modules associated with SZ, which can be used to study regulatory mechanisms underlying SZ at multiple levels. The proposed GSJNMF model projects multiple types of data onto a common feature space, in which heterogeneous variables with large coefficients on the same projected bases are used to identify multi-dimensional modules. We also incorporate group structure information available from each dataset. The genomic factors in such modules have significant correlations or functional associations with several brain activities. At the end, we have applied the method to the analysis of real data collected from the Mind Clinical Imaging Consortium (MCIC) for the study of SZ and identified significant biomarkers. These biomarkers were further used to discover genes and corresponding brain regions, which were confirmed to be significantly associated with SZ. [ABSTRACT FROM AUTHOR]

With the rapid development of high-throughput technologies, a growing amount of multi-omics data are collected, giving rise to a great demand for combining such data for biomedical discovery. Due to the cost and time to label the data manually, the number of labelled samples is limited. This motivated the need for semi-supervised learning algorithms. In this work, we applied a graph-based semi-supervised learning (GSSL) to classify a severe chronic mental disorder, schizophrenia (SZ). An advantage of GSSL is that it can simultaneously analyse more than two types of data, while many existing models focus on pairwise data analysis. In particular, we applied GSSL to the analysis of single nucleotide polymorphism (SNP), functional magnetic resonance imaging (fMRI) and DNA methylation data, which accounts for genetics, brain imaging (endophenotypes), and environmental factors (epigenomics) respectively. While parameter selection has been an open challenge for most models, another key contribution of this work is that we explored the parameter space to interpret their meaning and established practical guidelines. Based on the practical significance of each hyper-parameter, a relatively small range of candidate values can be determined in a data-driven way to both optimize and speed up the parameter tuning process. We validated the model through both synthetic data and a real SZ dataset of 184 subjects from the Mental Illness and Neuroscience Discovery (MIND) Clinical Imaging Consortium. In comparison to several existing approaches, our algorithm achieved better performance in terms of classification accuracy. We also confirmed the significance of several brain regions associated with SZ. [ABSTRACT FROM AUTHOR]

Recently, a hypergraph constructed from functional magnetic resonance imaging (fMRI) was utilized to explore brain functional connectivity networks (FCNs) for the classification of neurodegenerative diseases. Each edge of a hypergraph (called hyperedge) can connect any number of brain regions-of-interest (ROIs) instead of only two ROIs, and thus characterizes high-order relations among multiple ROIs that cannot be uncovered by a simple graph in the traditional graph based FCN construction methods. Unlike the existing hypergraph based methods where all hyperedges are assumed to have equal weights and only certain topological features are extracted from the hypergraphs, we propose a hypergraph learning based method for FCN construction in this paper. Specifically, we first generate hyperedges from fMRI time series based on sparse representation, then employ hypergraph learning to adaptively learn hyperedge weights, and finally define a hypergraph similarity matrix to represent the FCN. In our proposed method, weighting hyperedges results in better discriminative FCNs across subjects, and the defined hypergraph similarity matrix can better reveal the overall structure of brain network than using those hypergraph topological features. Moreover, we propose a multi-hypergraph learning based method by integrating multi-paradigm fMRI data, where the hyperedge weights associated with each fMRI paradigm are jointly learned and then a unified hypergraph similarity matrix is computed to represent the FCN. We validate the effectiveness of the proposed method on the Philadelphia Neurodevelopmental Cohort dataset for the classification of individuals’ learning ability from three paradigms of fMRI data. Experimental results demonstrate that our proposed approach outperforms the traditional graph based methods (i.e., Pearson’s correlation and partial correlation with the graphical Lasso) and the existing unweighted hypergraph based methods, which sheds light on how to optimize estimation of FCNs for cognitive and behavioral study. [ABSTRACT FROM AUTHOR]

Objective: Integration of multiple datasets is a hot topic in many fields. When studying complex mental disorders, great effort has been dedicated to fusing genetic and brain imaging data. However, an increasing number of studies have pointed out the importance of epigenetic factors in the cause of psychiatric diseases. In this study, we endeavor to fill the gap by combining epigenetics (e.g., DNA methylation) with imaging data (e.g., fMRI) to identify biomarkers for schizophrenia (SZ). Methods: We propose to combine linear regression with canonical correlation analysis (CCA) in a relaxed yet coupled manner to extract discriminative features for SZ that are co-expressed in the fMRI and DNA methylation data. Result: After validation through simulations, we applied our method to real imaging epigenetics data of 184 subjects from the Mental Illness and Neuroscience Discovery Clinical Imaging Consortium. After significance test, we identified 14 brain regions and 44 cytosine-phosphate-guanine(CpG) sites. Average classification accuracy is $\text{88.89}\%$. By linking the CpG sites to genes, we identified pathways Guanosine ribonucleotides de novo biosynthesis and Guanosine nucleotides de novo biosynthesis, and a GO term Perikaryon. Conclusion: This imaging epigenetics study has identified both brain regions and genes that are associated with neuron development and memory processing. These biomarkers contribute to a good understanding of the mechanism underlying SZ but are overlooked by previous imaging genetics studies. Significance: Our study sheds light on the understanding and diagnosis of SZ with a imaging epigenetics approach, which is demonstrated to be effective in extracting novel biomarkers associated with SZ. [ABSTRACT FROM AUTHOR]

Canonical polyadic decomposition (CPD) of multi-subject complex-valued fMRI data can be used to provide spatially and temporally shared components among groups with both magnitude and phase information. However, the CPD model is not well formulated due to the large subject variability in the spatial and temporal modalities, as well as the high noise level in complex-valued fMRI data. Considering that the shift-invariant CPD can model temporal variability across subjects, we propose to further impose a phase sparsity constraint on the shared spatial maps to denoise the complex-valued components and to model the inter-subject spatial variability as well. More precisely, subject-specific time delays are first estimated for the complex-valued shared time courses in the framework of real-valued shift-invariant CPD. Source phase sparsity is then imposed on the complex-valued shared spatial maps. A smoothed l0 norm is specifically used to reduce voxels with large phase values after phase de-ambiguity based on the small phase characteristic of BOLD-related voxels. The results from both the simulated and experimental fMRI data demonstrate improvements of the proposed method over three complex-valued algorithms, namely, tensor-based spatial ICA, shift-invariant CPD and CPD without spatiotemporal constraints. When comparing with a real-valued algorithm combining shift-invariant CPD and ICA, the proposed method detects 178.7% more contiguous task-related activations. [ABSTRACT FROM AUTHOR]

Objective: Multi-modal brain functional connectivity (FC) data have shown great potential for providing insights into individual variations in behavioral and cognitive traits. The joint learning of multi-modal data can utilize intrinsic association, and thus can boost learning performance. Although several multi-task based learning models have already been proposed by viewing feature learning on each modality as one task, most of them ignore the structural information inherent across the modalities, which may play an important role in extracting discriminative features. Methods: In this paper, we propose a new manifold regularized multi-task learning model by simultaneously considering between-subject and between-modality relationships. Specifically, the $l_{2,1}$ -norm (i.e., group-sparsity) regularizer is enforced to jointly select a few common features across different modalities. A novelly designed manifold regularizer is further imposed as a crucial underpinning to preserve the structural information both within and between modalities. Such designed regularizers will make our model more adaptive to realistic neuroimaging data, which are usually of small sample size but high dimensional features. Results: Our model is validated on the Philadelphia Neurodevelopmental Cohort dataset, where our modalities are regarded as two types of functional MRI (fMRI) data collected under two paradigms. We conduct experimental studies on fMRI-based FC network data in two task conditions for intelligence quotient (IQ) prediction. The results show that our proposed model can not only achieve improved prediction performance, but also yield a set of IQ-relevant biomarkers. Conclusion and Significance: This paper develops a new multi-task learning model, enabling the discovery of significant biomarkers that may account for a proportion of the variance in human intelligence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The study of healthy brain development helps to better understand both brain transformation and connectivity patterns, which happen during childhood to adulthood. This study presents a sparse machine learning solution across whole-brain functional connectivity measures of three datasets, derived from resting state functional magnetic resonance imaging (rs-fMRI) and two task fMRI data including a working memory n-back task (nb-fMRI) and an emotion identification task (em-fMRI). The fMRI data are collected from the Philadelphia Neurodevelopmental Cohort (PNC) for the prediction of brain age in adolescents. Due to extremely large variable-to-instance ratio of PNC data, a high-dimensional matrix with several irrelevant and highly correlated features is generated, and hence a sparse learning approach is necessary to extract effective features from fMRI data. We propose a sparse learner based on the residual errors along the estimation of an inverse problem for extreme learning machine (ELM). Our proposed method is able to overcome the overlearning problem by pruning several redundant features and their corresponding output weights. The proposed multimodal sparse ELM classifier based on residual errors is highly competitive in terms of classification accuracy compared to its counterparts such as conventional ELM, and sparse Bayesian learning ELM. [ABSTRACT FROM AUTHOR]

Objective: Multi-modal functional magnetic resonance imaging has been widely used for brain research. Conventional data-fusion methods cannot capture complex relationship (e.g., nonlinear predictive relationship) between multiple data. This paper aims to develop a neural network framework to extract phenotype related cross-data relationships and use it to study the brain development. Methods: We propose a novel method, deep collaborative learning (DCL), to address the limitation of existing methods. DCL first uses a deep network to represent original data and then seeks their correlations, while also linking the data representation with phenotypical information. Results: We studied the difference of functional connectivity (FCs) between different age groups and also use FCs as a fingerprint to predict cognitive abilities. Our experiments demonstrated higher accuracy of using DCL over other conventional models when classifying populations of different ages and cognitive scores. Moreover, DCL revealed that brain connections became stronger at adolescence stage. Furthermore, DCL detected strong correlations between default mode network and other networks which were overlooked by linear canonical correlation analysis, demonstrating DCL's ability of detecting nonlinear correlations. Conclusion: The results verified the superiority of DCL over conventional data-fusion methods. In addition, the stronger brain connection demonstrated the importance of adolescence stage for brain development. Significance: DCL can better combine complex correlations between multiple data sets in addition to their fitting to phenotypes, with the potential to overcome the limitations of several current data-fusion models. [ABSTRACT FROM AUTHOR]

Objective: To explain individual differences in development, behavior, and cognition, most previous studies focused on projecting resting-state functional MRI (fMRI) based functional connectivity (FC) data into a low-dimensional space via linear dimensionality reduction techniques, followed by executing analysis operations. However, linear dimensionality analysis techniques may fail to capture the nonlinearity of brain neuroactivity. Moreover, besides resting-state FC, the FC based on task fMRI can be expected to provide complementary information. Motivated by these considerations, we nonlinearly fuse resting-state and task-based FC networks (FCNs) to seek a better representation in this paper. Methods: We propose a framework based on alternating diffusion map (ADM), which extracts geometry-preserving low-dimensional embeddings that successfully parameterize the intrinsic variables driving the phenomenon of interest. Specifically, we first separately build resting-state and task-based FCNs by symmetric positive definite matrices using sparse inverse covariance estimation for each subject, and then utilize the ADM to fuse them in order to extract significant low-dimensional embeddings, which are used as fingerprints to identify individuals. Results: The proposed framework is validated on the Philadelphia Neurodevelopmental Cohort data, where we conduct extensive experimental study on resting-state and fractal $n$ -back task fMRI for the classification of intelligence quotient (IQ). The fusion of resting-state and $n$ -back task fMRI by the proposed framework achieves better classification accuracy than any single fMRI, and the proposed framework is shown to outperform several other data fusion methods. Conclusion and Significance: To our knowledge, this paper is the first to demonstrate a successful extension of the ADM to fuse resting-state and task-based fMRI data for accurate prediction of IQ. [ABSTRACT FROM AUTHOR]

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 project. Improved performance is achieved over the sliding window technique. In particular, group differences and transition behaviors 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. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) is a chronic and severe mental disorder that affects how a person thinks, feels, and behaves. It has been proposed that this disorder is related to disrupted brain connectivity, which has been verified by many studies. With the development of functional magnetic resonance imaging (fMRI), further exploration of brain connectivity was made possible. Region-based networks are commonly used for mapping brain connectivity. However, they fail to illustrate the connectivity within regions of interest (ROIs) and lose precise location information. Voxel-based networks provide higher precision, but are difficult to construct and interpret due to the high dimensionality of the data. In this paper, we adopt a novel high-dimensional Gaussian graphical model – $\psi$ -learning method, which can help ease computational burden and provide more accurate inference for the underlying networks. This method has been proven to be an equivalent measure of the partial correlation coefficient and, thus, is flexible for network comparison through statistical tests. The fMRI data we used were collected by the mind clinical imaging consortium using an auditory task in which there are 92 SZ patients and 116 healthy controls. We compared the networks at three different scales by using global measurements, community structure, and edge-wise comparisons within the networks. Our results reveal, at the highest voxel resolution, sets of distinct aberrant patterns for the SZ patients, and more precise local structures are provided within ROIs for further investigation. [ABSTRACT FROM AUTHOR]