Exploring dysconnectivity of the large-scale neurocognitive network across psychiatric disorders using spatiotemporal constrained nonnegative matrix factorization method.

Psychiatric disorders usually have similar clinical and neurobiological features. Nevertheless, previous research on functional dysconnectivity has mainly focused on a single disorder and the transdiagnostic alterations in brain networks remain poorly understood. Hence, this study proposed a spatiotemporal constrained nonnegative matrix factorization (STCNMF) method based on real reference signals to extract large-scale brain networks to identify transdiagnostic changes in neurocognitive networks associated with multiple diseases. Available temporal prior information and spatial prior information were first mined from the functional magnetic resonance imaging (fMRI) data of group participants, and then these prior constraints were incorporated into the nonnegative matrix factorization objective functions to improve their efficiency. The algorithm successfully obtained 10 resting-state functional brain networks in fMRI data of schizophrenia, bipolar disorder, attention deficit/hyperactivity disorder, and healthy controls, and further found transdiagnostic changes in these large-scale networks, including enhanced connectivity between right frontoparietal network and default mode network, reduced connectivity between medial visual network and default mode network, and the presence of a few hyper-integrated network nodes. Besides, each type of psychiatric disorder had its specific connectivity characteristics. These findings provide new insights into transdiagnostic and diagnosis-specific neurobiological mechanisms for understanding multiple psychiatric disorders from the perspective of brain networks.

Occupational functional plasticity revealed by brain entropy: A resting-state fMRI study of seafarers.

Recently, functional magnetic resonance imaging (fMRI) has been increasingly used to assess brain function. Brain entropy is an effective model for evaluating the alteration of brain complexity. Specifically, the sample entropy (SampEn) provides a feasible solution for revealing the brain's complexity. Occupation is one key factor affecting the brain's activity, but the neuropsychological mechanisms are still unclear. Thus, in this article, based on fMRI and a brain entropy model, we explored the functional complexity changes engendered by occupation factors, taking the seafarer as an example. The whole-brain entropy values of two groups (i.e., the seafarers and the nonseafarers) were first calculated by SampEn and followed by a two-sample t test with AlphaSim correction (p < .05). We found that the entropy of the orbital-frontal gyrus (OFG) and superior temporal gyrus (STG) in the seafarers was significantly higher than that of the nonseafarers. In addition, the entropy of the cerebellum in the seafarers was lower than that of the nonseafarers. We conclude that (1) the lower entropy in the cerebellum implies that the seafarers' cerebellum activity had strong regularity and consistency, suggesting that the seafarer's cerebellum was possibly more specialized by the long-term career training; (2) the higher entropy in the OFG and STG possibly demonstrated that the seafarers had a relatively decreased capability for emotion control and auditory information processing. The above results imply that the seafarer occupation indeed impacted the brain's complexity, and also provided new neuropsychological evidence of functional plasticity related to one's career.

Microcystin-LR degradation utilizing a novel effective indigenous bacterial community YFMCD1 from Lake Taihu.

Microcystins (MC) produced by species of cyanobacteria including Microcystis, Anabaena, and Aphanizomenon are a group of monocyclic hepatotoxins posing serious threat to public health. Microcystin-LR (MC-LR) is the most toxic and frequently encountered microcystin variant in the environment, and thus removal of this toxin using bacteria was shown to be a reliable, efficient, and cost-effective method that avoids utilization of chemicals that may produce potentially harmful by-products. The aim of this study was to determine whether a novel indigenous bacterial community designated YFMCD1 was effective in destroying MC. In addition, the influence of environmental factors such as temperature, MC concentration, and pH was examined on the effectiveness of YFMCD1 to degrade MC-LR. MC-degradation products were identified by high performance liquid chromatography coupled with an ultra-high resolution LTQ Orbitrap Velos Pro ETD mass spectrometry equipped with electrospray ionization interface (HPLC-ESI-MS). MC-LR underwent maximal degradation at rate of 0.5 µg/ml/hr with YFMCD1 containing Klebsiella sp. termed YFMCD1-1 or Stenotrophomonas sp. termed YFMCD1-2. Moreover, Adda (3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid) is a constituent within the MC-LR molecule found to be responsible for biological activity expression and critical for MC-induced toxicity, which is also degraded by YFMCD1. The results showed that YFMCD1 effectively degraded MC-LR. The degradation rate was significantly affected by temperature, pH, and MC-LR concentrations. Data indicate that this bacterial community may prove beneficial in bioremediation of lakes containing MC.

Exploring brain effective connectivity of early MCI with GRU_GC model on resting-state fMRI.

BACKGROUND: Investigating the functional interactions between different brain regions and revealing the transmission of information by computing brain connectivity have great potential and significance in the diagnosis of early Mild Cognitive Impairment (EMCI). METHODS: The Granger causality with Gate Recurrent Unit (GRU_GC) model is a suitable method that allows the detection of a nonlinear causal relationship and solves the limitation of fixed time lag, which cannot be detected by the classical Granger method. The model can transmit time series signals with any transmission delay length, and the time series can be screened and learned through the gate model. RESULTS: The classification experiment of 89 EMCI and 73 neurologically healthy controls (HC) shows that the accuracy reached 87.88%. Compared with multivariate variables GC (MVGC) and Long Short-Term Memory-based GC (LSTM_GC), the GRU_GC significantly improved the estimation of brain connectivity communication. Constructing a difference network to explore the brain effective connectivity between EMCI and HC. CONCLUSIONS: The GRU_GC can discover the abnormal brain regions, including the parahippocampal gyrus, the posterior cingulate gyrus. The method can be used in clinical applications as an effective brain connectivity analysis tool and provides auxiliary means for the medical diagnosis of EMCI.

A Novel High-Dimensional Kernel Joint Non-Negative Matrix Factorization With Multimodal Information for Lung Cancer Study.

Judging and identifying biological activities and biomarkers inside tissues from imaging features of diseases is challenging, so correlating pathological image data with genes inside organisms is of great significance for clinical diagnosis. This paper proposes a high-dimensional kernel non-negative matrix factorization (NMF) method based on muti-modal information fusion. This algorithm can project RNA gene expression data and pathological images (WSI) into a common feature space, where the heterogeneous variables with the largest coefficient in the same projection direction form a co-module. In addition, the miRNA-mRNA and miRNA-lncRNA interaction networks in the ceRNA network are added to the algorithm as a priori information to explore the relationship between the images and the internal activities of the gene. Furthermore, the radial basis kernel function is used to calculate the feature proportion between different kinds of genes mapped in the high-dimensional feature space and projected into the common feature space to explore the gene interaction in the high-dimensional situation. The original feature matrix is regularized to improve biological correlation, and the feature factors are sparse by orthogonal constraints to reduce redundancy. Experimental results show that the proposed NMF method is better than the traditional NMF method in stability, decomposition accuracy, and robustness. Through data analysis applied to lung cancer, genes related to tissue morphology are found, such as COL7A1, CENPF and BIRC5. In addition, gene pairs with a correlation degree exceeding 0.8 are found, and potential biomarkers of significant correlation with survival are obtained such as CAPN8. It has potential application value for the clinical diagnosis of lung cancer.

The safety and efficacy of neoadjuvant immunochemotherapy following laparoscopic gastrectomy for gastric cancer: a multicentre real-world clinical study.

BACKGROUND: The safety and efficacy of neoadjuvant immunochemotherapy (nICT) for locally advanced gastric cancer (LAGC) remain controversial. METHODS: Patients with LAGC who received either nICT or neoadjuvant chemotherapy (nCT) at 3 tertiary referral teaching hospitals in China between January 2016 and October 2022 were analyzed. After propensity-score matching (PSM), comparing the radiological response, pathological response rate, perioperative outcomes, and early recurrence between the two groups. RESULTS: After PSM, 585 patients were included, with 195 and 390 patients comprising the nICT and nCT groups, respectively. The nICT group exhibited a higher objective response rate (79.5% vs. 59.0%; P <0.001), pathological complete response rate (14.36% vs. 6.41%; P =0.002) and major pathological response rate (39.49% vs. 26.15%; P =0.001) compared with the nCT group. The incidence of surgical complications (17.44% vs. 16.15%, P =0.694) and the proportion of perioperative textbook outcomes (80.0% vs. 81.0%; P =0.767) were similar in both groups. The nICT group had a significantly lower proportion of early recurrence than the nCT group (29.7% vs. 40.8%; P =0.047). Furthermore, the multivariable logistic analysis revealed that immunotherapy was an independent protective factor against early recurrence [odds ratio 0.62 (95% CI 0.41-0.92); P =0.018]. No significant difference was found in neoadjuvant therapy drug toxicity between the two groups (51.79% vs. 45.38%; P =0.143). CONCLUSIONS: Compared with nCT, nICT is safe and effective, which significantly enhanced objective and pathological response rates and reduced the risk for early recurrence among patients with LAGC. TRIAL REGISTRATION: Clinical Trials.gov.

Sparse Independence Component Analysis for Competitive Endogenous RNA Co-Module Identification in Liver Hepatocellular Carcinoma.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been shown to be associated with the pathogenesis of different kinds of diseases and play important roles in various biological processes. Although numerous lncRNAs have been found, the functions of most lncRNAs and physiological/pathological significance are still in its infancy. Meanwhile, their expression patterns and regulation mechanisms are also far from being fully understood. METHODS: In order to reveal functional lncRNAs and identify the key lncRNAs, we develop a new sparse independence component analysis (ICA) method to identify lncRNA-mRNA-miRNA expression co-modules based on the competitive endogenous RNA (ceRNA) theory using the sample-matched lncRNA, mRNA and miRNA expression profiles. The expression data of the three RNA combined together is approximated sparsely to obtain the corresponding sparsity coefficient, and then it is decomposed by using ICA constraint optimization to obtain the common basis and modules. Subsequently, affine propagation clustering is used to perform cluster analysis on the common basis under multiple running conditions to obtain the co-modules for the selection of different RNA elements. RESULTS: We applied sparse ICA to Liver Hepatocellular Carcinoma (LIHC) dataset and the experiment results demonstrate that the proposed sparse ICA method can effectively discover biologically functional expression common modules. CONCLUSION: It may provide insights into the function of lncRNAs and molecular mechanism of LIHC. Clinical and Translational Impact Statement-The results on LIHC dataset demonstrate that the proposed sparse ICA method can effectively discover biologically functional expression common modules, which may provide insights into the function of IncRNAs and molecular mechanism of LIHC.

A schizophrenia study based on multi-frequency dynamic functional connectivity analysis of fMRI.

At present, fMRI studies mainly focus on the entire low-frequency band (0. 01-0.08 Hz). However, the neuronal activity is dynamic, and different frequency bands may contain different information. Therefore, a novel multi-frequency-based dynamic functional connectivity (dFC) analysis method was proposed in this study, which was then applied to a schizophrenia study. First, three frequency bands (Conventional: 0.01-0.08 Hz, Slow-5: 0.0111-0.0302 Hz, and Slow-4: 0.0302-0.0820 Hz) were obtained using Fast Fourier Transform. Next, the fractional amplitude of low-frequency fluctuations was used to identify abnormal regions of interest (ROIs) of schizophrenia, and dFC among these abnormal ROIs was implemented by the sliding time window method at four window-widths. Finally, recursive feature elimination was employed to select features, and the support vector machine was applied for the classification of patients with schizophrenia and healthy controls. The experimental results showed that the proposed multi-frequency method (Combined: Slow-5 and Slow-4) had a better classification performance compared with the conventional method at shorter sliding window-widths. In conclusion, our results revealed that the dFCs among the abnormal ROIs varied at different frequency bands and the efficiency of combining multiple features from different frequency bands can improve classification performance. Therefore, it would be a promising approach for identifying brain alterations in schizophrenia.

Classification of Migraine Using Static Functional Connectivity Strength and Dynamic Functional Connectome Patterns: A Resting-State fMRI Study.

Migraine is a common, chronic dysfunctional disease with recurrent headaches. Its etiology and pathogenesis have not been fully understood and there is a lack of objective diagnostic criteria and biomarkers. Meanwhile, resting-state functional magnetic resonance imaging (RS-fMRI) is increasingly being used in migraine research to classify and diagnose brain disorders. However, the RS-fMRI data is characterized by a large amount of data information and the difficulty of extracting high-dimensional features, which brings great challenges to relevant studies. In this paper, we proposed an automatic recognition framework based on static functional connectivity (sFC) strength features and dynamic functional connectome pattern (DFCP) features of migraine sufferers and normal control subjects, in which we firstly extracted sFC strength and DFCP features and then selected the optimal features using the recursive feature elimination based on the support vector machine (SVM-RFE) algorithm and, finally, trained and tested a classifier with the support vector machine (SVM) algorithm. In addition, we compared the classification performance of only using sFC strength features and DFCP features, respectively. The results showed that the DFCP features significantly outperformed sFC strength features in performance, which indicated that DFCP features had a significant advantage over sFC strength features in classification. In addition, the combination of sFC strength and DFCP features had the optimal performance, which demonstrated that the combination of both features could make full use of their advantage. The experimental results suggested the method had good performance in differentiating migraineurs and our proposed classification framework might be applicable for other mental disorders.

Occupation-modulated language networks and its lateralization: A resting-state fMRI study of seafarers.

Introduction: Studies have revealed that the language network of Broca's area and Wernicke's area is modulated by factors such as disease, gender, aging, and handedness. However, how occupational factors modulate the language network remains unclear. Methods: In this study, taking professional seafarers as an example, we explored the resting-state functional connectivity (RSFC) of the language network with seeds (the original and flipped Broca's area and Wernicke's area). Results: The results showed seafarers had weakened RSFC of Broca's area with the left superior/middle frontal gyrus and left precentral gyrus, and enhanced RSFC of Wernicke's area with the cingulate and precuneus. Further, seafarers had a less right-lateralized RSFC with Broca's area in the left inferior frontal gyrus, while the controls showed a left-lateralized RSFC pattern in Broca's area and a right-lateralized one in Wernicke's area. Moreover, seafarers displayed stronger RSFC with the left seeds of Broca's area and Wernicke's area. Discussion: These findings suggest that years of working experience significantly modulates the RSFC of language networks and their lateralization, providing rich insights into language networks and occupational neuroplasticity.

The integrative functional connectivity analysis between seafarer's brain networks using functional magnetic resonance imaging data of different states.

The particularity of seafarers' occupation makes their brain functional activities vulnerable to the influence of working environments, which leads to abnormal functional connectivities (FCs) between brain networks. To further investigate the influences of maritime environments on the seafarers' functional brain networks, the functional magnetic resonance imaging (fMRI) datasets of 33 seafarers before and after sailing were used to study FCs among the functional brain networks in this paper. On the basis of making full use of the intrinsic prior information from fMRI data, six resting-state brain functional networks of seafarers before and after sailing were obtained by using group independent component analysis with intrinsic reference, and then the differences between the static and dynamic FCs among these six brain networks of seafarers before and after sailing were, respectively, analyzed from both group and individual levels. Subsequently, the potential dynamic functional connectivity states of seafarers before and after sailing were extracted by using the affine propagation clustering algorithm and the probabilities of state transition between them were obtained simultaneously. The results show that the dynamic FCs among large-scale brain networks have significant difference seafarers before and after sailing both at the group level and individual level, while the static FCs between them varies only at the individual level. This suggests that the maritime environments can indeed affect the brain functional activity of seafarers in real time, and the degree of influence is different for different subjects, which is of a great significance to explore the neural changes of seafarer's brain functional network.

A Novel Key Features Screening Method Based on Extreme Learning Machine for Alzheimer's Disease Study.

The Extreme Learning Machine (ELM) is a simple and efficient Single Hidden Layer Feedforward Neural Network(SLFN) algorithm. In recent years, it has been gradually used in the study of Alzheimer's disease (AD). When using ELM to diagnose AD based on high-dimensional features, there are often some features that have no positive impact on the diagnosis, while others have a significant impact on the diagnosis. In this paper, a novel Key Features Screening Method based on Extreme Learning Machine (KFS-ELM) is proposed. It can screen for key features that are relevant to the classification (diagnosis). It can also assign weights to key features based on their importance. We designed an experiment to screen for key features of AD. A total of 920 key functional connections screened from 4005 functional connections. Their weights were also obtained. The results of the experiment showed that: (1) Using all (4,005) features to diagnose AD, the accuracy is 95.33%. Using 920 key features to diagnose AD, the accuracy is 99.20%. The 3,085 (4,005 - 920) features that were screened out had a negative effect on the diagnosis of AD. This indicates the KFS-ELM is effective in screening key features. (2) The higher the weight of the key features and the smaller their number, the greater their impact on AD diagnosis. This indicates that the KFS-ELM is rational in assigning weights to the key features for their importance. Therefore, KFS-ELM can be used as a tool for studying features and also for improving classification accuracy.

Brain Response of Major Depressive Disorder Patients to Emotionally Positive and Negative Music.

Depression is characterized by poor emotion regulation that makes it difficult to escape the effects of emotional pain, but the neuromodulation behind these symptoms is still unclear. This study investigated the neural mechanism of emotional state-related responses during music stimuli in participants with major depressive disorder (MDD) compared to never-depressed (ND) controls. A novel two-level feature selection method, integrating recursive feature elimination based on support vector machine (SVM-RFE) and random forest algorithm (RF), was proposed to screen emotional recognition brain regions (ERBRs). On this basis, the differences of functional connectivity (FC) were systematically analyzed by two-sample t-test. The results demonstrate that ND participants show eight pairs of FCs with a significant difference between positive emotional music stimuli (pEMS) versus negative emotional music stimuli (nEMS) in 15 ERBRs of MDD, but the participants with MDD show one pair of significant difference in FC. The decreased number reflects the fuzzy response to positive and negative emotions in MDD, which appears to arise from obstacle to emotional cognition and regulation. Furthermore, there was no significant difference in FC between MDDs and NDs under pEMS, but a significant difference was detected between the two groups under nEMS (p < 0.01), revealing a 'bias' against the negative state in MDD. The current study may help to better comprehend the abnormal evolution from normal to depression and inform the utilization of pEMS in formal treatment for depression.

An Attention-Based 3D CNN With Multi-Scale Integration Block for Alzheimer's Disease Classification.

Convolutional Neural Networks (CNNs) have recently been introduced to Alzheimer's Disease (AD) diagnosis. Despite their encouraging prospects, most of the existing models only process AD-related brain atrophy on a single spatial scale, and have high computational complexity. Here, we propose a novel Attention-based 3D Multi-scale CNN model (AMSNet), which can better capture and integrate multiple spatial-scale features of AD, with a concise structure. For the binary classification between 384 AD patients and 389 Cognitively Normal (CN) controls using sMRI scannings, AMSNet achieves remarkable overall performance (91.3% accuracy, 88.3% sensitivity, and 94.2% specificity) with fewer parameters and lower computational load, generally surpassing seven comparative models. Furthermore, AMSNet generalizes well in other AD-related classification tasks, such as the three-way classification (AD-MCI-CN). Our results manifest the feasibility and efficiency of the proposed multi-scale spatial feature integration and attention mechanism used in AMSNet for AD classification, and provide potential biomarkers to explore the neuropathological causes of AD.

A Novel Constrained Non-negative Matrix Factorization Method for Group Functional Magnetic Resonance Imaging Data Analysis of Adult Attention-Deficit/Hyperactivity Disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. Extracting brain networks from functional magnetic resonance imaging (fMRI) data can help explore neurocognitive disorders in adult ADHD. However, there is still a lack of effective methods to extract large-scale brain networks to identify disease-related brain network changes. Hence, this study proposed a spatial constrained non-negative matrix factorization (SCNMF) method based on the fMRI real reference signal. First, non-negative matrix factorization analysis was carried out on each subject to select the brain network components of interest. Subsequently, the available spatial prior information was mined by integrating the interested components of all subjects. This prior constraint was then incorporated into the NMF objective function to improve its efficiency. For the sake of verifying the effectiveness and feasibility of the proposed method, we quantitatively compared the SCNMF method with other classical algorithms and applied it to the dynamic functional connectivity analysis framework. The algorithm successfully extracted ten resting-state brain functional networks from fMRI data of adult ADHD and healthy controls and found large-scale brain network changes in adult ADHD patients, such as enhanced connectivity between executive control network and right frontoparietal network. In addition, we found that older ADHD spent more time in the pattern of relatively weak connectivity. These findings indicate that the method can effectively extract large-scale functional networks and provide new insights into understanding the neurobiological mechanisms of adult ADHD from the perspective of brain networks.

Dynamical Complexity Fingerprints of Occupation-Dependent Brain Functional Networks in Professional Seafarers.

The complexity derived from resting-state functional magnetic resonance imaging (rs-fMRI) data has been applied for exploring cognitive states and occupational neuroplasticity. However, there is little information about the influence of occupational factors on dynamic complexity and topological properties of the connectivity networks. In this paper, we proposed a novel dynamical brain complexity analysis (DBCA) framework to explore the changes in dynamical complexity of brain activity at the voxel level and complexity topology for professional seafarers caused by long-term working experience. The proposed DBCA is made up of dynamical brain entropy mapping analysis and complex network analysis based on brain entropy sequences, which generate the dynamical complexity of local brain areas and the topological complexity across brain areas, respectively. First, the transient complexity of voxel-wise brain map was calculated; compared with non-seafarers, seafarers showed decreased dynamic entropy values in the cerebellum and increased values in the left fusiform gyrus (BA20). Further, the complex network analysis based on brain entropy sequences revealed small-worldness in terms of topological complexity in both seafarers and non-seafarers, indicating that it is an inherent attribute of human the brain. In addition, seafarers showed a higher average path length and lower average clustering coefficient than non-seafarers, suggesting that the information processing ability is reduced in seafarers. Moreover, the reduction in efficiency of seafarers suggests that they have a less efficient processing network. To sum up, the proposed DBCA is effective for exploring the dynamic complexity changes in voxel-wise activity and region-wise connectivity, showing that occupational experience can reshape seafarers' dynamic brain complexity fingerprints.

Improving Health Literacy: Analysis of the Relationship between Residents' Usage of Information Channels and Health Literacy in Shanghai, China.

Background: This study aimed to examine the relationship between residents' health literacy (HL) and their use of and trust in information channels. Methods: A community-based cross-sectional health survey utilizing a cluster sampling design was conducted in January 2022. The sample consisted of 1067 residents in Shanghai, China. Those who correctly answered over 80% of the questions were regarded as qualified. The differences in residents' HL and the dimensions of knowledge HL, lifestyle HL, and skills HL were analyzed based on their use of and trust in traditional media, the internet, and offline activities. Logistic regression was conducted to examine the effects of the usage of these channels on all four types of HL. Results: A total of 27.65% of participants were qualified for HL. The use of traditional media (OR = 1.405, p < 0.05) and engagement in offline activities (OR = 1.951, p < 0.05) were significantly related to HL. Disbelief in traditional media was related to being qualified in knowledge HL (OR = 1.262; p < 0.05), whereas disbelief in offline activities had an adverse effect on knowledge HL and skills HL (OR = 0.700, 0.807; p < 0.05). Conclusion: Effort should be made to improve the efficiency of offline health education, and ensure the reliability and quality of health-related information from mass media and the internet to improve residents' HL.

The Brain Alteration of Seafarer Revealed by Activated Functional Connectivity Mode in fMRI Data Analysis.

As a special occupational group, the working and living environments faced by seafarers are greatly different from those of land. It is easy to affect the psychological and physiological activities of seafarers, which inevitably lead to changes in the brain functional activities of seafarers. Therefore, it is of great significance to study the neural activity rules of seafarers' brain. In view of this, this paper studied the seafarers' brain alteration at the activated voxel level based on functional magnetic resonance imaging technology by comparing the differences in functional connectivities (FCs) between seafarers and non-seafarers. Firstly, the activated voxels of each group were obtained by independence component analysis, and then the distribution of these voxels in the brain and the common activated voxels between the two groups were statistically analyzed. Next, the FCs between the common activated voxels of the two groups were calculated and obtained the FCs that had significant differences between them through two-sample T-test. Finally, all FCs and FCs with significant differences (DFCs) between the common activated voxels were used as the features for the support vector machine to classify seafarers and non-seafarers. The results showed that DFCs between the activated voxels had better recognition ability for seafarers, especially for Precuneus_L and Precuneus_R, which may play an important role in the classification prediction of seafarers and non-seafarers, so that provided a new perspective for studying the specificity of neurological activities of seafarers.

Internet-like brain hierarchical network model: Alzheimer's disease study as an example.

BACKGROUND AND OBJECTIVE: The modular structure and hierarchy are important topological characteristics in real complex networks such as brain networks on temporal scale. However, there are few studies investigating the hierarchical structure at the spatial scale of brain networks, the application of which still remains to be further studied. METHODS: In this study, a novel model of brain hierarchical network based on the hierarchical characteristic of Internet topology is proposed for the first time, which is called Internet-like brain hierarchical network (IBHN). In this model, the whole brain network is partitioned into multiple levels: brain wide area network (Brain-WAN), brain metropolitan network (Brain-MAN), and brain local area network (Brain-LAN). A Brain-MAN is formed by the interconnection of multiple Brain-LANs, and the interconnection of multiple Brain-MANs forms a Brain-WAN. A multivariate analysis method is employed to measure overall functional connectivity between two brain networks at the same network level rather than detecting the change of each node pair's functional connection. Furthermore, we demonstrate the utility of IBHN model with application to a practical case-control study involving 64 patients with Alzheimer's disease and 75 healthy controls. RESULTS: The proposed model identified enhanced functional connectivity (P-value<0.05) at Brain-WAN level and reduced functional connectivity (P-value=0.004) at Brain-LAN level of Alzheimer's disease patients, which can be used as a multi-dimension functional reference for AD's diagnosis. CONCLUSIONS: This study not only provides insight into AD pathophysiology, but also further proves the effectiveness of the proposed IBHN model. In addition, the IBHN model makes it possible to explore the brain's functional organization from multiple dimensions and offers a multi-level perspective for the research of complex brain network.

Brain Relatively Inert Network: Taking Adult Attention Deficit Hyperactivity Disorder as an Example.

Resting-state functional MRI (rs-fMRI) has been increasingly applied in the research of brain cognitive science and psychiatric diseases. However, previous studies only focused on specific activation areas of the brain, and there are few studies on the inactivation areas. This may overlook much information that explains the brain's cognitive function. In this paper, we propose a relatively inert network (RIN) and try to explore its important role in understanding the cognitive mechanism of the brain and the study of mental diseases, using adult attention deficit hyperactivity disorder (ADHD) as an example. Here, we utilize methods based on group independent component analysis (GICA) and t-test to identify RIN and calculate its corresponding time series. Through experiments, alterations in the RIN and the corresponding activation network (AN) in adult ADHD patients are observed. And compared with those in the left brain, the activation changes in the right brain are greater. Further, when the RIN functional connectivity is introduced as a feature to classify adult ADHD patients from healthy controls (HCs), the classification accuracy rate is 12% higher than that of the original functional connectivity feature. This was also verified by testing on an independent public dataset. These findings confirm that the RIN of the brain contains much information that will probably be neglected. Moreover, this research provides an effective new means of exploring the information integration between brain regions and the diagnosis of mental illness.