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Yuhui Du

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17 papers

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JBHI Journal 2026 Journal Article

Group Information Guided Smooth Independent Component Analysis Method for Multi-Subject fMRI Data Analysis

Yuhui Du
Chen Huang
Vince D. Calhoun

Group independent component analysis (ICA) has been extensively used to extract brain functional networks (FNs) and associated neuroimaging measures from multi-subject functional magnetic resonance imaging (fMRI) data. However, the inherent noise in fMRI data can adversely affect the performance of ICA, often leading to noisy FNs and hindering the identification of network-level biomarkers. To address this challenge, we propose a novel method called group information guided smooth independent component analysis (GIG-sICA). Our method effectively generates smoother functional networks with reduced noise and enhanced functional coherence, while preserving intra-subject independence and inter-subject correspondence of FN. Importantly, GIG-sICA is capable of handling different types of noise either separately or in combination. To validate the efficacy of our approach, we conducted comprehensive experiments, comparing GIG-sICA with traditional group ICA methods on both simulated and real fMRI datasets. Experiments on five simulated datasets, generated by adding various types of noise, demonstrate that GIG-sICA produces smoother functional networks with enhanced spatial accuracy. Additionally, experiments on real fMRI data from 137 schizophrenia patients and 144 healthy controls demonstrate that GIG-sICA more effectively captures functionally meaningful brain networks and reveals clearer group differences. Overall, GIG-sICA produces smooth and precise network estimations, supporting the discovery of robust biomarkers at the network level for neuroscience research.

JBHI Journal 2025 Journal Article

An orthogonal semi-nonnegative matrix factorization method for dynamic functional connectivity analysis and its application to schizophrenia

Xingyu He
Vince D. Calhoun
Godfrey D. Pearlson
Peter Kochunov
Theo G.M. van Erp
Yuhui Du

Dynamic functional connectivity (dFC) analysis investigates how the functional interactions between brain regions change over time by identifying recurring connectivity patterns, known as dFC states, and tracking transitions between them. Non-negative matrix factorization (NMF) has been used in dFC analysis because it produces non-negative dFC states and coefficients, interpreting dFC states and their transitions straightforwardly. However, existing NMF-based methods are limited to processing dFC data with exclusively positive values, failing to align with the functional correlations and anti-correlations between brain regions. This paper proposes an orthogonal semi-nonnegative matrix factorization (OSemiNMF) method, extending NMF to directly handle mixed-sign dFC data. Furthermore, an orthogonality constraint on the bases (i. e. , dFC states) is incorporated to enhance the uniqueness of dFC states. For 10 simulated datasets with varying properties, our method outperforms comparison methods, supporting its superior ability to capture dFC states and state transitions. Using four resting-state fMRI datasets consisting of 708 healthy controls (HCs) and 537 schizophrenia patients (SZs), our method identifies reproducible dFC states and state transitions across datasets. Further, our findings reveal that SZs spend less time in high-connectivity states compared to HCs. Our study identifies meaningful and reproducible biomarkers of schizophrenia, mainly involving the connectivity associated with the sub-cortical domain. In summary, the OSemiNMF method facilitates the dFC analysis for understanding brain dynamics.

YNIMG Journal 2024 Journal Article

Local-structure-preservation and redundancy-removal-based feature selection method and its application to the identification of biomarkers for schizophrenia

Ying Xing
Godfrey D. Pearlson
Peter Kochunov
Vince D. Calhoun
Yuhui Du

Accurate diagnosis of mental disorders is expected to be achieved through the identification of reliable neuroimaging biomarkers with the help of cutting-edge feature selection techniques. However, existing feature selection methods often fall short in capturing the local structural characteristics among samples and effectively eliminating redundant features, resulting in inadequate performance in disorder prediction. To address this gap, we propose a novel supervised method named local-structure-preservation and redundancy-removal-based feature selection (LRFS), and then apply it to the identification of meaningful biomarkers for schizophrenia (SZ). LRFS method leverages graph-based regularization to preserve original sample similarity relationships during data transformation, thus retaining crucial local structure information. Additionally, it introduces redundancy-removal regularization based on interrelationships among features to exclude similar and redundant features from high-dimensional data. Moreover, LRFS method incorporates l 2, 1 sparse regularization that enables selecting a sparse and noise-robust feature subset. Experimental evaluations on eight public datasets with diverse properties demonstrate the superior performance of our method over nine popular feature selection methods in identifying discriminative features, with average classification accuracy gains ranging from 1. 30 % to 9. 11 %. Furthermore, the LRFS method demonstrates superior discriminability in four functional magnetic resonance imaging (fMRI) datasets from 708 healthy controls (HCs) and 537 SZ patients, with an average increase in classification accuracy ranging from 1. 89 % to 9. 24 % compared to other nine methods. Notably, our method reveals reproducible and significant changes in SZ patients relative to HCs across the four datasets, predominantly in the thalamus-related functional network connectivity, which exhibit a significant correlation with clinical symptoms. Convergence analysis, parameter sensitivity analysis, and ablation studies further demonstrate the effectiveness and robustness of our method. In short, our proposed feature selection method effectively identifies discriminative and reliable features that hold the potential to be biomarkers, paving the way for the elucidation of brain abnormalities and the advancement of precise diagnosis of mental disorders.

YNIMG Journal 2024 Journal Article

Searching Reproducible Brain Features using NeuroMark: Templates for Different Age Populations and Imaging Modalities

Zening Fu
Ishaan Batta
Lei Wu
Anees Abrol
Oktay Agcaoglu
Mustafa S Salman
Yuhui Du
Armin Iraji

A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations.

JBHI Journal 2023 Journal Article

A Novel Neighborhood Rough Set-Based Feature Selection Method and Its Application to Biomarker Identification of Schizophrenia

Ying Xing
Peter Kochunov
Theo G.M. van Erp
Tianzhou Ma
Vince D. Calhoun
Yuhui Du

Feature selection can disclose biomarkers of mental disorders that have unclear biological mechanisms. Although neighborhood rough set (NRS) has been applied to discover important sparse features, it has hardly ever been utilized in neuroimaging-based biomarker identification, probably due to the inadequate feature evaluation metric and incomplete information provided under a single-granularity. Here, we propose a new NRS-based feature selection method and successfully identify brain functional connectivity biomarkers of schizophrenia (SZ) using functional magnetic resonance imaging (fMRI) data. Specifically, we develop a new weighted metric based on NRS combined with information entropy to evaluate the capacity of features in distinguishing different groups. Inspired by multi-granularity information maximization theory, we further take advantage of the complementary information from different neighborhood sizes via a multi-granularity fusion to obtain the most discriminative and stable features. For validation, we compare our method with six popular feature selection methods using three public omics datasets as well as resting-state fMRI data of 393 SZ patients and 429 healthy controls. Results show that our method obtained higher classification accuracies on both omics data (100. 0%, 88. 6%, and 72. 2% for three omics datasets, respectively) and fMRI data (93. 9% for main dataset, and 76. 3% and 83. 8% for two independent datasets, respectively). Moreover, our findings reveal biologically meaningful substrates of SZ, notably involving the connectivity between the thalamus and superior temporal gyrus as well as between the postcentral gyrus and calcarine gyrus. Taken together, we propose a new NRS-based feature selection method that shows the potential of exploring effective and sparse neuroimaging-based biomarkers of mental disorders.

YNICL Journal 2020 Journal Article

Identifying commonality and specificity across psychosis sub-groups via classification based on features from dynamic connectivity analysis

Yuhui Du
Hui Hao
Shuhua Wang
Godfrey D Pearlson
Vince D. Calhoun

It is difficult to distinguish schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar disorder with psychosis (BPP) as their clinical diagnoses rely on symptoms that overlap. In this paper, we investigate if there is biological evidence to support the symptom-based clinical categories by looking across the three disorders using dynamic connectivity measures, and provide meaningful characteristics on which brain functional connectivity measures are commonly or uniquely impaired. Large-sample functional magnetic resonance image (fMRI) datasets from 623 subjects including 238 healthy controls (HCs), 113 SZ patients, 132 SAD patients, and 140 BPP patients were analyzed. First, we computed whole-brain dynamic functional connectivity (DFC) using a sliding-window technique, and then extracted the individual connectivity states by applying our previously proposed decomposition-based DFC analysis method. Next, with the features from the dominant connectivity state, we assessed the clinical categories by performing both four-group (SZ, SAD, BPP and healthy control groups) and pair-wise classification using a support vector machine within cross-validation. Furthermore, we comprehensively summarized the shared and unique connectivity alterations among the disorders. In terms of the classification performance, our method achieved 69% in the four-group classification and >80% in the between-group classifications for the mean overall accuracy; and yielded 66% in the four-group classification and >80% in the between-group classifications for the mean balanced accuracy. Through summarizing the features that were automatically selected in the classifications, we found that among the three symptom-related disorders, their disorder-common impairments primarily included the decreased connectivity strength between thalamus and cerebellum and the increased strength between postcentral gyrus and thalamus. The disorder-unique changes included more various brain regions, mainly in the temporal and frontal gyrus. Our work demonstrates that dynamic functional connectivity provides biological evidence that both common and unique impairments exist in psychosis sub-groups.

YNICL Journal 2020 Journal Article

NeuroMark: An automated and adaptive ICA based pipeline to identify reproducible fMRI markers of brain disorders

Yuhui Du
Zening Fu
Jing Sui
Shuang Gao
Ying Xing
Dongdong Lin
Mustafa Salman
Anees Abrol

Many mental illnesses share overlapping or similar clinical symptoms, confounding the diagnosis. It is important to systematically characterize the degree to which unique and similar changing patterns are reflective of brain disorders. Increasing sharing initiatives on neuroimaging data have provided unprecedented opportunities to study brain disorders. However, it is still an open question on replicating and translating findings across studies. Standardized approaches for capturing reproducible and comparable imaging markers are greatly needed. Here, we propose a pipeline based on the priori-driven independent component analysis, NeuroMark, which is capable of estimating brain functional network measures from functional magnetic resonance imaging (fMRI) data that can be used to link brain network abnormalities among different datasets, studies, and disorders. NeuroMark automatically estimates features adaptable to each individual subject and comparable across datasets/studies/disorders by taking advantage of the reliable brain network templates extracted from 1828 healthy controls as guidance. Four studies including 2442 subjects were conducted spanning six brain disorders (schizophrenia, autism spectrum disorder, mild cognitive impairment, Alzheimer's disease, bipolar disorder, and major depressive disorder) to evaluate validity of the proposed pipeline from different perspectives (replication of brain abnormalities, cross-study comparison, identification of subtle brain changes, and multi-disorder classification using identified biomarkers). Our results highlight that NeuroMark effectively identified replicated brain network abnormalities of schizophrenia across different datasets; revealed interesting neural clues on the overlap and specificity between autism and schizophrenia; demonstrated brain functional impairments present to varying degrees in mild cognitive impairments and Alzheimer's disease; and captured biomarkers that achieved good performance in classifying bipolar disorder and major depressive disorder.

YNICL Journal 2019 Journal Article

Group ICA for identifying biomarkers in schizophrenia: ‘Adaptive’ networks via spatially constrained ICA show more sensitivity to group differences than spatio-temporal regression

Mustafa S. Salman
Yuhui Du
Dongdong Lin
Zening Fu
Alex Fedorov
Eswar Damaraju
Jing Sui
Jiayu Chen

Brain functional networks identified from fMRI data can provide potential biomarkers for brain disorders. Group independent component analysis (GICA) is popular for extracting brain functional networks from multiple subjects. In GICA, different strategies exist for reconstructing subject-specific networks from the group-level networks. However, it is unknown whether these strategies have different sensitivities to group differences and abilities in distinguishing patients. Among GICA, spatio-temporal regression (STR) and spatially constrained ICA approaches such as group information guided ICA (GIG-ICA) can be used to propagate components (indicating networks) to a new subject that is not included in the original subjects. In this study, based on the same a priori network maps, we reconstructed subject-specific networks using these two methods separately from resting-state fMRI data of 151 schizophrenia patients (SZs) and 163 healthy controls (HCs). We investigated group differences in the estimated functional networks and the functional network connectivity (FNC) obtained by each method. The networks were also used as features in a cross-validated support vector machine (SVM) for classifying SZs and HCs. We selected features using different strategies to provide a comprehensive comparison between the two methods. GIG-ICA generally showed greater sensitivity in statistical analysis and better classification performance (accuracy 76.45 ± 8.9%, sensitivity 0.74 ± 0.11, specificity 0.79 ± 0.11) than STR (accuracy 67.45 ± 8.13%, sensitivity 0.65 ± 0.11, specificity 0.71 ± 0.11). Importantly, results were also consistent when applied to an independent dataset including 82 HCs and 82 SZs. Our work suggests that the functional networks estimated by GIG-ICA are more sensitive to group differences, and GIG-ICA is promising for identifying image-derived biomarkers of brain disease.

YNIMG Journal 2019 Journal Article

Transient increased thalamic-sensory connectivity and decreased whole-brain dynamism in autism

Zening Fu
Yiheng Tu
Xin Di
Yuhui Du
Jing Sui
Bharat B. Biswal
Zhiguo Zhang
N. de Lacy

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with social communication deficits and restricted/repetitive behaviors and is characterized by large-scale atypical subcortical-cortical connectivity, including impaired resting-state functional connectivity between thalamic and sensory regions. Previous studies have typically focused on the abnormal static connectivity in ASD and overlooked potential valuable dynamic patterns in brain connectivity. However, resting-state brain connectivity is indeed highly dynamic, and abnormalities in dynamic brain connectivity have been widely identified in psychiatric disorders. In this study, we investigated the dynamic functional network connectivity (dFNC) between 51 intrinsic connectivity networks in 170 individuals with ASD and 195 age-matched typically developing (TD) controls using independent component analysis and a sliding window approach. A hard clustering state analysis and a fuzzy meta-state analysis were conducted respectively, for the exploration of local and global aberrant dynamic connectivity patterns in ASD. We examined the group difference in dFNC between thalamic and sensory networks in each functional state and group differences in four high-dimensional dynamic measures. The results showed that compared with TD controls, individuals with ASD show an increase in transient connectivity between hypothalamus/subthalamus and some sensory networks (right postcentral gyrus, bi paracentral lobule, and lingual gyrus) in certain functional states, and diminished global meta-state dynamics of the whole-brain functional network. In addition, these atypical dynamic patterns are significantly associated with autistic symptoms indexed by the Autism Diagnostic Observation Schedule. These converging results support and extend previous observations regarding hyperconnectivity between thalamic and sensory regions and stable whole-brain functional configuration in ASD. Dynamic brain connectivity may serve as a potential biomarker of ASD and further investigation of these dynamic patterns might help to advance our understanding of behavioral differences in this complex neurodevelopmental disorder.

YNIMG Journal 2018 Journal Article

Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia

Zening Fu
Yiheng Tu
Xin Di
Yuhui Du
G.D. Pearlson
J.A. Turner
Bharat B. Biswal
Zhiguo Zhang

The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder.

YNIMG Journal 2018 Journal Article

Dynamic functional connectivity impairments in early schizophrenia and clinical high-risk for psychosis

Yuhui Du
Susanna L. Fryer
Zening Fu
Dongdong Lin
Jing Sui
Jiayu Chen
Eswar Damaraju
Eva Mennigen

Individuals at clinical high-risk (CHR) for psychosis are characterized by attenuated psychotic symptoms. Only a minority of CHR individuals convert to full-blown psychosis. Therefore, there is a strong interest in identifying neurobiological abnormalities underlying the psychosis risk syndrome. Dynamic functional connectivity (DFC) captures time-varying connectivity over short time scales, and has the potential to reveal complex brain functional organization. Based on resting-state functional magnetic resonance imaging (fMRI) data from 70 healthy controls (HCs), 53 CHR individuals, and 58 early illness schizophrenia (ESZ) patients, we applied a novel group information guided ICA (GIG-ICA) to estimate inherent connectivity states from DFC, and then investigated group differences. We found that ESZ patients showed more aberrant connectivities and greater alterations than CHR individuals. Results also suggested that disease-related connectivity states occurred in CHR and ESZ groups. Regarding the dominant state with the highest contribution to dynamic connectivity, ESZ patients exhibited greater impairments than CHR individuals primarily in the cerebellum, frontal cortex, thalamus and temporal cortex, while CHR and ESZ populations shared common aberrances mainly in the supplementary motor area, parahippocampal gyrus and postcentral cortex. CHR-specific changes were also found in the connections between the superior frontal gyrus and calcarine cortex in the dominant state. Our findings suggest that CHR individuals generally show an intermediate functional connectivity pattern between HCs and SZ patients but also have unique connectivity alterations.

YNICL Journal 2018 Journal Article

Identifying functional network changing patterns in individuals at clinical high-risk for psychosis and patients with early illness schizophrenia: A group ICA study

Yuhui Du
Susanna L. Fryer
Dongdong Lin
Jing Sui
Qingbao Yu
Jiayu Chen
Barbara Stuart
Rachel L. Loewy

Although individuals at clinical high risk (CHR) for psychosis exhibit a psychosis-risk syndrome involving attenuated forms of the positive symptoms typical of schizophrenia (SZ), it remains unclear whether their resting-state brain intrinsic functional networks (INs) show attenuated or qualitatively distinct patterns of functional dysconnectivity relative to SZ patients. Based on resting-state functional magnetic imaging data from 70 healthy controls (HCs), 53 CHR individuals (among which 41 subjects were antipsychotic medication-naive), and 58 early illness SZ (ESZ) patients (among which 53 patients took antipsychotic medication) within five years of illness onset, we estimated subject-specific INs using a novel group information guided independent component analysis (GIG-ICA) and investigated group differences in INs. We found that when compared to HCs, both CHR and ESZ groups showed significant differences, primarily in default mode, salience, auditory-related, visuospatial, sensory-motor, and parietal INs. Our findings suggest that widespread INs were diversely impacted. More than 25% of voxels in the identified significant discriminative regions (obtained using all 19 possible changing patterns excepting the no-difference pattern) from six of the 15 interrogated INs exhibited monotonically decreasing Z-scores (in INs) from the HC to CHR to ESZ, and the related regions included the left lingual gyrus of two vision-related networks, the right postcentral cortex of the visuospatial network, the left thalamus region of the salience network, the left calcarine region of the fronto-occipital network and fronto-parieto-occipital network. Compared to HCs and CHR individuals, ESZ patients showed both increasing and decreasing connectivity, mainly hypo-connectivity involving 15% of the altered voxels from four INs. The left supplementary motor area from the sensory-motor network and the right inferior occipital gyrus in the vision-related network showed a common abnormality in CHR and ESZ groups. Some brain regions also showed a CHR-unique alteration (primarily the CHR-increasing connectivity). In summary, CHR individuals generally showed intermediate connectivity between HCs and ESZ patients across multiple INs, suggesting that some dysconnectivity patterns evident in ESZ predate psychosis in attenuated form during the psychosis risk stage. Hence, these connectivity measures may serve as possible biomarkers to predict schizophrenia progression.

YNIMG Journal 2017 Journal Article

Predicting individualized clinical measures by a generalized prediction framework and multimodal fusion of MRI data

Xing Meng
Rongtao Jiang
Dongdong Lin
Juan Bustillo
Thomas Jones
Jiayu Chen
Qingbao Yu
Yuhui Du

Neuroimaging techniques have greatly enhanced the understanding of neurodiversity (human brain variation across individuals) in both health and disease. The ultimate goal of using brain imaging biomarkers is to perform individualized predictions. Here we proposed a generalized framework that can predict explicit values of the targeted measures by taking advantage of joint information from multiple modalities. This framework also enables whole brain voxel-wise searching by combining multivariate techniques such as ReliefF, clustering, correlation-based feature selection and multiple regression models, which is more flexible and can achieve better prediction performance than alternative atlas-based methods. For 50 healthy controls and 47 schizophrenia patients, three kinds of features derived from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy) were extracted and fed into a regression model, achieving high prediction for both cognitive scores (MCCB composite r =0. 7033, MCCB social cognition r =0. 7084) and symptomatic scores (positive and negative syndrome scale [PANSS] positive r =0. 7785, PANSS negative r =0. 7804). Moreover, the brain areas likely responsible for cognitive deficits of schizophrenia, including middle temporal gyrus, dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with different weights, as well as regions predicting PANSS symptoms, including thalamus, striatum and inferior parietal lobule, pinpointing the potential neuromarkers. Finally, compared to a single modality, multimodal combination achieves higher prediction accuracy and enables individualized prediction on multiple clinical measures. There is more work to be done, but the current results highlight the potential utility of multimodal brain imaging biomarkers to eventually inform clinical decision-making.

YNIMG Journal 2015 Journal Article

A group ICA based framework for evaluating resting fMRI markers when disease categories are unclear: application to schizophrenia, bipolar, and schizoaffective disorders

Yuhui Du
Godfrey D. Pearlson
Jingyu Liu
Jing Sui
Qingbao Yu
Hao He
Eduardo Castro
Vince D. Calhoun

Schizophrenia (SZ), bipolar disorder (BP) and schizoaffective disorder (SAD) share some common symptoms, and there is still a debate about whether SAD is an independent category. To the best of our knowledge, no study has been done to differentiate these three disorders or to investigate the distinction of SAD as an independent category using fMRI data. This study is aimed to explore biomarkers from resting-state fMRI networks for differentiating these disorders and investigate the relationship among these disorders based on fMRI networks with an emphasis on SAD. Firstly, a novel group ICA method, group information guided independent component analysis (GIG-ICA), was applied to extract subject-specific brain networks from fMRI data of 20 healthy controls (HC), 20 SZ patients, 20 BP patients, 20 patients suffering from SAD with manic episodes (SADM), and 13 patients suffering from SAD with depressive episodes exclusively (SADD). Then, five-level one-way analysis of covariance and multiclass support vector machine recursive feature elimination were employed to identify discriminative regions from the networks. Subsequently, the t-distributed stochastic neighbor embedding (t-SNE) projection and the hierarchical clustering were implemented to investigate the relationship among those groups. Finally, to evaluate the generalization ability, 16 new subjects were classified based on the found regions and the trained model using original 93 subjects. Results show that the discriminative regions mainly included frontal, parietal, precuneus, cingulate, supplementary motor, cerebellar, insula and supramarginal cortices, which performed well in distinguishing different groups. SADM and SADD were the most similar to each other, although SADD had greater similarity to SZ compared to other groups, which indicates that SAD may be an independent category. BP was closer to HC compared with other psychotic disorders. In summary, resting-state fMRI brain networks extracted via GIG-ICA provide a promising potential to differentiate SZ, BP, and SAD.

YNIMG Journal 2015 Journal Article

Assessing dynamic brain graphs of time-varying connectivity in fMRI data: Application to healthy controls and patients with schizophrenia

Qingbao Yu
Erik B. Erhardt
Jing Sui
Yuhui Du
Hao He
Devon Hjelm
Mustafa S. Cetin
Srinivas Rachakonda

Graph theory-based analysis has been widely employed in brain imaging studies, and altered topological properties of brain connectivity have emerged as important features of mental diseases such as schizophrenia. However, most previous studies have focused on graph metrics of stationary brain graphs, ignoring that brain connectivity exhibits fluctuations over time. Here we develop a new framework for accessing dynamic graph properties of time-varying functional brain connectivity in resting-state fMRI data and apply it to healthy controls (HCs) and patients with schizophrenia (SZs). Specifically, nodes of brain graphs are defined by intrinsic connectivity networks (ICNs) identified by group independent component analysis (ICA). Dynamic graph metrics of the time-varying brain connectivity estimated by the correlation of sliding time-windowed ICA time courses of ICNs are calculated. First- and second-level connectivity states are detected based on the correlation of nodal connectivity strength between time-varying brain graphs. Our results indicate that SZs show decreased variance in the dynamic graph metrics. Consistent with prior stationary functional brain connectivity works, graph measures of identified first-level connectivity states show lower values in SZs. In addition, more first-level connectivity states are disassociated with the second-level connectivity state which resembles the stationary connectivity pattern computed by the entire scan. Collectively, the findings provide new evidence about altered dynamic brain graphs in schizophrenia, which may underscore the abnormal brain performance in this mental illness.

YNIMG Journal 2013 Journal Article

Group information guided ICA for fMRI data analysis

Yuhui Du
Yong Fan

Group independent component analysis (ICA) has been widely applied to studies of multi-subject fMRI data for computing subject specific independent components with correspondence across subjects. However, the independence of subject specific independent components (ICs) derived from group ICA has not been explicitly optimized in existing group ICA methods. In order to preserve independence of ICs at the subject level and simultaneously establish correspondence of ICs across subjects, we present a new framework for obtaining subject specific ICs, which we coined group-information guided ICA (GIG-ICA). In this framework, group information captured by standard ICA on the group level is exploited as guidance to compute individual subject specific ICs using a multi-objective optimization strategy. Specifically, we propose a framework with two stages: at first, group ICs (GICs) are obtained using standard group ICA tools, and then the GICs are used as references in a new one-unit ICA with spatial reference (ICA-R) using a multi-objective optimization solver. Comparison experiments with back-reconstruction (GICA1 and GICA3) and dual regression on simulated and real fMRI data have demonstrated that GIG-ICA is able to obtain subject specific ICs with stronger independence and better spatial correspondence across different subjects in addition to higher spatial and temporal accuracy.

YNIMG Journal 2013 Journal Article

Groupwise spatial normalization of fMRI data based on multi-range functional connectivity patterns

Di Jiang
Yuhui Du
Hewei Cheng
Tianzi Jiang
Yong Fan

Spatial alignment of functional magnetic resonance images (fMRI) of different subjects is a necessary precursor to improve functional consistency across subjects for group analysis in fMRI studies. Traditional structural MRI (sMRI) based registration methods cannot achieve accurate inter-subject functional consistency in that functional units are not necessarily located relative to anatomical structures consistently due to functional variability across subjects. Although spatial smoothing commonly used in fMRI data preprocessing can reduce the inter-subject functional variability, it may blur the functional signals and thus lose the fine-grained information. To overcome the limitations of exiting techniques, in this paper, we propose a novel method for spatial normalization of fMRI data by matching their multi-range functional connectivity patterns progressively. In particular, the image registration of different subjects is achieved by maximizing inter-subject similarity of their functional images' local functional connectivity patterns that characterize functional connectivity information for each voxel of the images to its spatial neighbors. The neighborhood size for computing the local functional connectivity patterns is gradually increased with the progression of image registration to capture the functional connectivity information in larger ranges. We also adopt the congealing groupwise image registration strategy to simultaneously warp a group of subjects to an unbiased template. Experimental comparisons between the proposed method and other fMRI image registration methods have demonstrated that the proposed method could achieve superior registration performance for resting state fMRI data. Experiment results based on real resting-state fMRI data have further demonstrated that the proposed fMRI registration method can achieve a statistically significant improvement in functional consistency across subjects.