High-order Functional Connectivity Research Articles

Multi-Order Brain Functional Connectivity Network-Based Machine Learning Method for Recognition of Delayed Neurocognitive Recovery in Older Adults Undergoing Non-cardiac Surgery.

Objectives: Delayed neurocognitive recovery (DNR) seriously affects the post-operative recovery of elderly surgical patients, but there is still a lack of effective methods to recognize high-risk patients with DNR. This study proposed a machine learning method based on a multi-order brain functional connectivity (FC) network to recognize DNR.Method: Seventy-four patients who completed assessments were included in this study, in which 16/74 (21.6%) had DNR following surgery. Based on resting-state functional magnetic resonance imaging (rs-fMRI), we first constructed low-order FC networks of 90 brain regions by calculating the correlation of brain region signal changing in the time dimension. Then, we established high-order FC networks by calculating correlations among each pair of brain regions. Afterward, we built sparse representation-based machine learning model to recognize DNR on the extracted multi-order FC network features. Finally, an independent testing was conducted to validate the established recognition model.Results: Three hundred ninety features of FC networks were finally extracted to identify DNR. After performing the independent-sample T test between these features and the categories, 15 features showed statistical differences (P < 0.05) and 3 features had significant statistical differences (P < 0.01). By comparing DNR and non-DNR patients’ brain region connection matrices, it is found that there are more connections among brain regions in DNR patients than in non-DNR patients. For the machine learning recognition model based on multi-feature combination, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the classifier reached 95.61, 92.00, 66.67, and 100.00%, respectively.Conclusion: This study not only reveals the significance of preoperative rs-fMRI in recognizing post-operative DNR in elderly patients but also establishes a promising machine learning method to recognize DNR.

Constructing high-order functional connectivity network based on central moment features for diagnosis of autism spectrum disorder.

The sliding-window-based dynamic functional connectivity network (D-FCN) has been becoming an increasingly useful tool for understanding the changes of brain connectivity patterns and the association of neurological diseases with these dynamic variations. However, conventional D-FCN is essentially low-order network, which only reflects the pairwise interaction pattern between brain regions and thus overlooking the high-order interactions among multiple brain regions. In addition, D-FCN is innate with temporal sensitivity issue, i.e., D-FCN is sensitive to the chronological order of its subnetworks. To deal with the above issues, we propose a novel high-order functional connectivity network framework based on the central moment feature of D-FCN. Specifically, we firstly adopt a central moment approach to extract multiple central moment feature matrices from D-FCN. Furthermore, we regard the matrices as the profiles to build multiple high-order functional connectivity networks which further capture the higher level and more complex interaction relationships among multiple brain regions. Finally, we use the voting strategy to combine the high-order networks with D-FCN for autism spectrum disorder diagnosis. Experimental results show that the combination of multiple functional connectivity networks achieves accuracy of 88.06%, and the best single network achieves accuracy of 79.5%.

Classification of type 2 diabetes mellitus with or without cognitive impairment from healthy controls using high-order functional connectivity.

Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and may progress to dementia. However, the brain functional mechanism of T2DM‐related dementia is still less understood. Recent resting‐state functional magnetic resonance imaging functional connectivity (FC) studies have proved its potential value in the study of T2DM with cognitive impairment (T2DM‐CI). However, they mainly used a mass‐univariate statistical analysis that was not suitable to reveal the altered FC “pattern” in T2DM‐CI, due to lower sensitivity. In this study, we proposed to use high‐order FC to reveal the abnormal connectomics pattern in T2DM‐CI with a multivariate, machine learning‐based strategy. We also investigated whether such patterns were different between T2DM‐CI and T2DM without cognitive impairment (T2DM‐noCI) to better understand T2DM‐induced cognitive impairment, on 23 T2DM‐CI and 27 T2DM‐noCI patients, as well as 50 healthy controls (HCs). We first built the large‐scale high‐order brain networks based on temporal synchronization of the dynamic FC time series among multiple brain region pairs and then used this information to classify the T2DM‐CI (as well as T2DM‐noCI) from the matched HC based on support vector machine. Our model achieved an accuracy of 79.17% in T2DM‐CI versus HC differentiation, but only 59.62% in T2DM‐noCI versus HC classification. We found abnormal high‐order FC patterns in T2DM‐CI compared to HC, which was different from that in T2DM‐noCI. Our study indicates that there could be widespread connectivity alterations underlying the T2DM‐induced cognitive impairment. The results help to better understand the changes in the central neural system due to T2DM.

Recognition of Cognitive Impairment in Adult Moyamoya Disease: A Classifier Based on High-Order Resting-State Functional Connectivity Network.

Objective: Vascular cognitive impairment (VCI) is a common complication in adult patients with moyamoya disease (MMD), and is reversible by surgical revascularization in its early stage of mild VCI. However, accurate diagnosis of mild VCI is difficult based on neuropsychological examination alone. This study proposed a method of dynamic resting-state functional connectivity (FC) network to recognize global cognitive impairment in MMD.Methods: For MMD, 36 patients with VCI and 43 patients with intact cognition (Non-VCI) were included, as well as 26 normal controls (NCs). Using resting-state fMRI, dynamic low-order FC networks were first constructed with multiple brain regions which were generated through a sliding window approach and correlated in temporal dimension. In order to obtain more information of network interactions along the time, high-order FC networks were established by calculating correlations among each pair of brain regions. Afterwards, a sparse representation-based classifier was constructed to recognize MMD (experiment 1) and its cognitive impairment (experiment 2) with features extracted from both low- and high-order FC networks. Finally, the ten-fold cross-validation strategy was proposed to train and validate the performance of the classifier.Results: The three groups did not differ significantly in demographic features (p > 0.05), while the VCI group exhibited the lowest MMSE scores (p = 0.001). The Non-VCI and NCs groups did not differ significantly in MMSE scores (p = 0.054). As for the classification between MMD and NCs, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the classifier reached 90.70, 88.57, 93.67, and 73.08%, respectively. While for the classification between VCI and Non-VCI, the AUC, accuracy, sensitivity, and specificity of the classifier reached 91.02, 84.81, 80.56, and 88.37%, respectively.Conclusion: This study not only develops a promising classifier to recognize VCI in adult MMD in its early stage, but also implies the significance of time-varying properties in dynamic FC networks.

High-Order Functional Connectivity Network for Differential Diagnosis of Depression

Resting-state functional connectivity (FC) changes dynamically and major depressive disorder (MDD) has abnormality in functional connectivity networks (FCNs), but few existing resting-state fMRI study on MDD utilizes the dynamics, especially for identifying depressive individuals from healthy controls. In this paper, we propose a methodological procedure for differential diagnosis of depression, called HN3D, which is based on high-order functional connectivity networks (HFCN). Firstly, HN3D extracts time series by independent component analysis, and partitions them into overlapped short series by sliding time window. Secondly, it constructs a FCN for each time window and concatenates correlation matrices of all FCNs to generate correlation time series. Then, correlation time series are grouped into different clusters and high-order correlations for HFCN is calculated based on their means. Finally, graph based features of HFCNs are extracted and selected for a linear discriminative classifier. Tested on 21 healthy controls and 20 MDD patients, HN3D achieved its best 100% classification accuracy, which is much higher than results based on stationary FCNs. In addition, most discriminative components of HN3D locate in default mode network and visual network, which are consistent with existing stationary-based results on depression. Though HN3D needs to be studied further, it is helpful for the differential diagnosis of depression and might have potentiality in identifying relevant biomarkers.

Fusion of ULS Group Constrained High- and Low-Order Sparse Functional Connectivity Networks for MCI Classification.

Functional connectivity networks, derived from resting-state fMRI data, have been found as effective biomarkers for identifying mild cognitive impairment (MCI) from healthy elderly. However, the traditional functional connectivity network is essentially a low-order network with the assumption that the brain activity is static over the entire scanning period, ignoring temporal variations among the correlations derived from brain region pairs. To overcome this limitation, we proposed a new type of sparse functional connectivity network to precisely describe the relationship of temporal correlations among brain regions. Specifically, instead of using the simple pairwise Pearson's correlation coefficient as connectivity, we first estimate the temporal low-order functional connectivity for each region pair based on an ULS Group constrained-UOLS regression algorithm, where a combination of ultra-least squares (ULS) criterion with a Group constrained topology structure detection algorithm is applied to detect the topology of functional connectivity networks, aided by an Ultra-Orthogonal Least Squares (UOLS) algorithm to estimate connectivity strength. Compared to the classical least squares criterion which only measures the discrepancy between the observed signals and the model prediction function, the ULS criterion takes into consideration the discrepancy between the weak derivatives of the observed signals and the model prediction function and thus avoids the overfitting problem. By using a similar approach, we then estimate the high-order functional connectivity from the low-order connectivity to characterize signal flows among the brain regions. We finally fuse the low-order and the high-order networks using two decision trees for MCI classification. Experimental results demonstrate the effectiveness of the proposed method on MCI classification.

Inter-Network High-Order Functional Connectivity (IN-HOFC) and its Alteration in Patients with Mild Cognitive Impairment.

Little is known about the high-order interactions among brain regions measured by the similarity of higher-order features (other than the raw blood-oxygen-level-dependent signals) which can characterize higher-level brain functional connectivity (FC). Previously, we proposed FC topographical profile-based high-order FC (HOFC) and found that this metric could provide supplementary information to traditional FC for early Alzheimer's disease (AD) detection. However, whether such findings apply to network-level brain functional integration is unknown. In this paper, we propose an extended HOFC method, termed inter-network high-order FC (IN-HOFC), as a useful complement to the traditional inter-network FC methods, for characterizing more complex organizations among the large-scale brain networks. In the IN-HOFC, both network definition and inter-network FC are defined in a high-order manner. To test whether IN-HOFC is more sensitive to cognition decline due to brain diseases than traditional inter-network FC, 77 mild cognitive impairments (MCIs) and 89 controls are compared among the conventional methods and our IN-HOFC. The result shows that IN-HOFCs among three temporal lobe-related high-order networks are dampened in MCIs. The impairment of IN-HOFC is especially found between the anterior and posterior medial temporal lobe and could be a potential MCI biomarker at the network level. The competing network-level low-order FC methods, however, either revealing less or failing to detect any group difference. This work demonstrates the biological meaning and potential diagnostic value of the IN-HOFC in clinical neuroscience studies.

Between-Frequency Topographical and Dynamic High-Order Functional Connectivity for Driving Drowsiness Assessment.

Previous studies exploring driving drowsiness utilized spectral power and functional connectivity without considering between-frequency and more complex synchronizations. To complement such lacks, we explored inter-regional synchronizations based on the topographical and dynamic properties between frequency bands using high-order functional connectivity (HOFC) and envelope correlation. We proposed the dynamic interactions of HOFC, associated-HOFC, and a global metric measuring the aggregated effect of the functional connectivity. The EEG dataset was collected from 30 healthy subjects, undergoing two driving sessions. The two-session setting was employed for evaluating the metric reliability across sessions. Based on the results, we observed reliably significant metric changes, mainly involving the alpha band. In HOFCθα , HOFCαβ , associated- HOFCθα , and associated- HOFCαβ , the connection-level metrics in frontal-central, central-central, and central-parietal/occipital areas were significantly increased, indicating a dominance in the central region. Similar results were also obtained in the HOFCθαβ and aHOFCθαβ . For dynamic-low-order-FC and dynamic-HOFC, the global metrics revealed a reliably significant increment in the alpha, theta-alpha, and alpha-beta bands. Modularity indexes of associated- HOFCα and associated- HOFCθα also exhibited reliably significant differences. This paper demonstrated that within-band and between-frequency topographical and dynamic FC can provide complementary information to the traditional individual-band LOFC for assessing driving drowsiness.

Improving Sparsity and Modularity of High-Order Functional Connectivity Networks for MCI and ASD Identification.

High-order correlation has recently been proposed to model brain functional connectivity network (FCN) for identifying neurological disorders, such as mild cognitive impairment (MCI) and autism spectrum disorder (ASD). In practice, the high-order FCN (HoFCN) can be derived from multiple low-order FCNs that are estimated separately in a series of sliding windows, and thus it in fact provides a way of integrating dynamic information encoded in a sequence of low-order FCNs. However, the estimation of low-order FCN may be unreliable due to the fact that the use of limited volumes/samples in a sliding window can significantly reduce the statistical power, which in turn affects the reliability of the resulted HoFCN. To address this issue, we propose to enhance HoFCN based on a regularized learning framework. More specifically, we first calculate an initial HoFCN using a recently developed method based on maximum likelihood estimation. Then, we learn an optimal neighborhood network of the initially estimated HoFCN with sparsity and modularity priors as regularizers. Finally, based on the improved HoFCNs, we conduct experiments to identify MCI and ASD patients from their corresponding normal controls. Experimental results show that the proposed methods outperform the baseline methods, and the improved HoFCNs with modularity prior consistently achieve the best performance.

Strength and similarity guided group-level brain functional network construction for MCI diagnosis

Sparse representation-based brain functional network modeling often results in large inter-subject variability in the network structure. This could reduce the statistical power in group comparison, or even deteriorate the generalization capability of the individualized diagnosis of brain diseases. Although group sparse representation (GSR) can alleviate such a limitation by increasing network similarity across subjects, it could, in turn, fail in providing satisfactory separability between the subjects from different groups (e.g., patients vs. controls). In this study, we propose to integrate individual functional connectivity (FC) information into the GSR-based network construction framework to achieve higher between-group separability while maintaining the merit of within-group consistency. Our method was based on an observation that the subjects from the same group have generally more similar FC patterns than those from different groups. To this end, we propose our new method, namely “strength and similarity guided GSR (SSGSR)”, which exploits both BOLD signal temporal correlation-based “low-order” FC (LOFC) and inter-subject LOFC-profile similarity-based “high-order” FC (HOFC) as two priors to jointly guide the GSR-based network modeling. Extensive experimental comparisons are carried out, with the rs-fMRI data from mild cognitive impairment (MCI) subjects and healthy controls, between the proposed algorithm and other state-of-the-art brain network modeling approaches. Individualized MCI identification results show that our method could achieve a balance between the individually consistent brain functional network construction and the adequately maintained inter-group brain functional network distinctions, thus leading to a more accurate classification result. Our method also provides a promising and generalized solution for the future connectome-based individualized diagnosis of brain disease.

Overall survival time prediction for high-grade glioma patients based on large-scale brain functional networks

High-grade glioma (HGG) is a lethal cancer with poor outcome. Accurate preoperative overall survival (OS) time prediction for HGG patients is crucial for treatment planning. Traditional presurgical and noninvasive OS prediction studies have used radiomics features at the local lesion area based on the magnetic resonance images (MRI). However, the highly complex lesion MRI appearance may have large individual variability, which could impede accurate individualized OS prediction. In this paper, we propose a novel concept, namely brain connectomics-based OS prediction. It is based on presurgical resting-state functional MRI (rs-fMRI) and the non-local, large-scale brain functional networks where the global and systemic prognostic features rather than the local lesion appearance are used to predict OS. We propose that the connectomics features could capture tumor-induced network-level alterations that are associated with prognosis. We construct both low-order (by means of sparse representation with regional rs-fMRI signals) and high-order functional connectivity (FC) networks (characterizing more complex multi-regional relationship by synchronized dynamics FC time courses). Then, we conduct a graph-theoretic analysis on both networks for a jointly, machine-learning-based individualized OS prediction. Based on a preliminary dataset (N = 34 with bad OS, mean OS, ~400days; N = 34 with good OS, mean OS, ~1030days), we achieve a promising OS prediction accuracy (86.8%) on separating the individuals with bad OS from those with good OS. However, if using only conventionally derived descriptive features (e.g., age and tumor characteristics), the accuracy is low (63.2%). Our study highlights the importance of the rs-fMRI and brain functional connectomics for treatment planning.

Diagnosis of Autism Spectrum Disorders Using Multi-Level High-Order Functional Networks Derived From Resting-State Functional MRI.

Functional brain networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) have been widely used for Autism Spectrum Disorder (ASD) diagnosis. Typically, these networks are constructed by calculating functional connectivity (FC) between any pair of brain regions of interest (ROIs), i.e., using Pearson's correlation between rs-fMRI time series. However, this can only be called as a low-order representation of the functional interaction, because the relationship is investigated just between two ROIs. Brain disorders might not only affect low-order FC, but also high-order FC, i.e., the higher-level relationship among multiple brain regions, which might be more crucial for diagnosis. To comprehensively characterize such relationship for better diagnosis of ASD, we propose a multi-level, high-order FC network representation that can nicely capture complex interactions among brain regions. Then, we design a feature selection method to identify those discriminative multi-level, high-order FC features for ASD diagnosis. Finally, we design an ensemble classifier with multiple linear SVMs, each trained on a specific level of FC networks, for boosting the final classification accuracy. Experimental results show that the integration of both low-order and first-level high-order FC networks achieves the best ASD diagnostic accuracy (81%). We further investigated those selected discriminative low-order and high-order FC features and found that the high-order FC features can provide complementary information to the low-order FC features in the ASD diagnosis.

Simultaneous Estimation of Low- and High-Order Functional Connectivity for Identifying Mild Cognitive Impairment.

Functional connectivity (FC) network has been becoming an increasingly useful tool for understanding the cerebral working mechanism and mining sensitive biomarkers for neural/mental disease diagnosis. Currently, Pearson's Correlation (PC) is the simplest and most commonly used scheme in FC estimation. Despite its empirical effectiveness, PC only encodes the low-order (i.e., second-order) statistics by calculating the pairwise correlations between network nodes (brain regions), which fails to capture the high-order information involved in FC (e.g., the correlations among different edges in a network). To address this issue, we propose a novel FC estimation method based on Matrix Variate Normal Distribution (MVND), which can capture both low- and high-order correlations simultaneously with a clear mathematical interpretability. Specifically, we first generate a set of BOLD subseries by the sliding window scheme, and for each subseries we construct a temporal FC network by PC. Then, we employ the constructed FC networks as samples to estimate the final low- and high-order FC networks by maximizing the likelihood of MVND. To illustrate the effectiveness of the proposed method, we conduct experiments to identify subjects with Mild Cognitive Impairment (MCI) from Normal Controls (NCs). Experimental results show that the fusion of low- and high-order FCs can generally help to improve the final classification performance, even though the high-order FC may contain less discriminative information than its low-order counterpart. Importantly, the proposed method for simultaneous estimation of low- and high-order FCs can achieve better classification performance than the two baseline methods, i.e., the original PC method and a recent high-order FC estimation method.

Alzheimer Classification Using a Minimum Spanning Tree of High-Order Functional Network on fMRI Dataset.

Functional magnetic resonance imaging (fMRI) is one of the most useful methods to generate functional connectivity networks of the brain. However, conventional network generation methods ignore dynamic changes of functional connectivity between brain regions. Previous studies proposed constructing high-order functional connectivity networks that consider the time-varying characteristics of functional connectivity, and a clustering method was performed to decrease computational cost. However, random selection of the initial clustering centers and the number of clusters negatively affected classification accuracy, and the network lost neurological interpretability. Here we propose a novel method that introduces the minimum spanning tree method to high-order functional connectivity networks. As an unbiased method, the minimum spanning tree simplifies high-order network structure while preserving its core framework. The dynamic characteristics of time series are not lost with this approach, and the neurological interpretation of the network is guaranteed. Simultaneously, we propose a multi-parameter optimization framework that involves extracting discriminative features from the minimum spanning tree high-order functional connectivity networks. Compared with the conventional methods, our resting-state fMRI classification method based on minimum spanning tree high-order functional connectivity networks greatly improved the diagnostic accuracy for Alzheimer's disease.

Test-Retest Reliability of "High-Order" Functional Connectivity in Young Healthy Adults.

Functional connectivity (FC) has become a leading method for resting-state functional magnetic resonance imaging (rs-fMRI) analysis. However, the majority of the previous studies utilized pairwise, temporal synchronization-based FC. Recently, high-order FC (HOFC) methods were proposed with the idea of computing “correlation of correlations” to capture high-level, more complex associations among the brain regions. There are two types of HOFC. The first type is topographical profile similarity-based HOFC (tHOFC) and its variant, associated HOFC (aHOFC), for capturing different levels of HOFC. Instead of measuring the similarity of the original rs-fMRI signals with the traditional FC (low-order FC, or LOFC), tHOFC measures the similarity of LOFC profiles (i.e., a set of LOFC values between a region and all other regions) between each pair of brain regions. The second type is dynamics-based HOFC (dHOFC) which defines the quadruple relationship among every four brain regions by first calculating two pairwise dynamic LOFC “time series” and then measuring their temporal synchronization (i.e., temporal correlation of the LOFC fluctuations, not the BOLD fluctuations). Applications have shown the superiority of HOFC in both disease biomarker detection and individualized diagnosis than LOFC. However, no study has been carried out for the assessment of test-retest reliability of different HOFC metrics. In this paper, we systematically evaluate the reliability of the two types of HOFC methods using test-retest rs-fMRI data from 25 (12 females, age 24.48 ± 2.55 years) young healthy adults with seven repeated scans (with interval = 3–8 days). We found that all HOFC metrics have satisfactory reliability, specifically (1) fair-to-good for tHOFC and aHOFC, and (2) fair-to-moderate for dHOFC with relatively strong connectivity strength. We further give an in-depth analysis of the biological meanings of each HOFC metric and highlight their differences compared to the LOFC from the aspects of cross-level information exchanges, within-/between-network connectivity, and modulatory connectivity. In addition, how the dynamic analysis parameter (i.e., sliding window length) affects dHOFC reliability is also investigated. Our study reveals unique functional associations characterized by the HOFC metrics. Guidance and recommendations for future applications and clinical research using HOFC are provided. This study has made a further step toward unveiling more complex human brain connectome.

Hybrid High-order Functional Connectivity Networks Using Resting-state Functional MRI for Mild Cognitive Impairment Diagnosis

Conventional functional connectivity (FC), referred to as low-order FC, estimates temporal correlation of the resting-state functional magnetic resonance imaging (rs-fMRI) time series between any pair of brain regions, simply ignoring the potentially high-level relationship among these brain regions. A high-order FC based on “correlation’s correlation” has emerged as a new approach for abnormality detection of brain disease. However, separate construction of the low- and high-order FC networks overlooks information exchange between the two FC levels. Such a higher-level relationship could be more important for brain diseases study. In this paper, we propose a novel framework, namely “hybrid high-order FC networks” by exploiting the higher-level dynamic interaction among brain regions for early mild cognitive impairment (eMCI) diagnosis. For each sliding window-based rs-fMRI sub-series, we construct a whole-brain associated high-order network, by estimating the correlations between the topographical information of the high-order FC sub-network from one brain region and that of the low-order FC sub-network from another brain region. With multi-kernel learning, complementary features from multiple time-varying FC networks constructed at different levels are fused for eMCI classification. Compared with other state-of-the-art methods, the proposed framework achieves superior diagnosis accuracy, and hence could be promising for understanding pathological changes of brain connectome.

Hierarchical High-Order Functional Connectivity Networks and Selective Feature Fusion for MCI Classification.

Conventional Functional connectivity (FC) analysis focuses on characterizing the correlation between two brain regions, whereas the high-order FC can model the correlation between two brain region pairs. To reduce the number of brain region pairs, clustering is applied to group all the brain region pairs into a small number of clusters. Then, a high-order FC network can be constructed based on the clustering result. By varying the number of clusters, multiple high-order FC networks can be generated and the one with the best overall performance can be finally selected. However, the important information contained in other networks may be simply discarded. To address this issue, in this paper, we propose to make full use of the information contained in all high-order FC networks. First, an agglomerative hierarchical clustering technique is applied such that the clustering result in one layer always depends on the previous layer, thus making the high-order FC networks in the two consecutive layers highly correlated. As a result, the features extracted from high-order FC network in each layer can be decomposed into two parts (blocks), i.e., one is redundant while the other might be informative or complementary, with respect to its previous layer. Then, a selective feature fusion method, which combines sequential forward selection and sparse regression, is developed to select a feature set from those informative feature blocks for classification. Experimental results confirm that our novel method outperforms the best single high-order FC network in diagnosis of mild cognitive impairment (MCI) subjects.

Machine-Learning Classifier for Patients with Major Depressive Disorder: Multifeature Approach Based on a High-Order Minimum Spanning Tree Functional Brain Network.

High-order functional connectivity networks are rich in time information that can reflect dynamic changes in functional connectivity between brain regions. Accordingly, such networks are widely used to classify brain diseases. However, traditional methods for processing high-order functional connectivity networks generally include the clustering method, which reduces data dimensionality. As a result, such networks cannot be effectively interpreted in the context of neurology. Additionally, due to the large scale of high-order functional connectivity networks, it can be computationally very expensive to use complex network or graph theory to calculate certain topological properties. Here, we propose a novel method of generating a high-order minimum spanning tree functional connectivity network. This method increases the neurological significance of the high-order functional connectivity network, reduces network computing consumption, and produces a network scale that is conducive to subsequent network analysis. To ensure the quality of the topological information in the network structure, we used frequent subgraph mining technology to capture the discriminative subnetworks as features and combined this with quantifiable local network features. Then we applied a multikernel learning technique to the corresponding selected features to obtain the final classification results. We evaluated our proposed method using a data set containing 38 patients with major depressive disorder and 28 healthy controls. The experimental results showed a classification accuracy of up to 97.54%.

Fusion of High-Order and Low-Order Effective Connectivity Networks for MCI Classification.

Functional connectivity network derived from resting-state fMRI data has been found as effective biomarkers for identifying patients with mild cognitive impairment from healthy elderly. However, the ordinary functional connectivity network is essentially a low-order network with the assumption that the brain is static during the entire scanning period, ignoring the temporal variations among correlations derived from brain region pairs. To overcome this weakness, we proposed a new type of high-order network to more accurately describe the relationship of temporal variations among brain regions. Specifically, instead of the commonly used undirected pairwise Pearson's correlation coefficient, we first estimated the low-order effective connectivity network based on a novel sparse regression algorithm. By using the similar approach, we then constructed the high-order effective connectivity network from low-order connectivity to incorporate signal flow information among the brain regions. We finally combined the low-order and the high-order effective connectivity networks using two decision trees for MCI classification and experimental results obtained demonstrate the superiority of the proposed method over the conventional undirected low-order and high-order functional connectivity networks, as well as the low-order and high-order effective connectivity networks when they were used separately.

Hybrid High-order Functional Connectivity Networks Using Resting-state Functional MRI for Mild Cognitive Impairment Diagnosis

Hybrid High-order Functional Connectivity Networks Using Resting-state Functional MRI for Mild Cognitive Impairment Diagnosis