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Spinocerebellar ataxia type 3 (SCA3) is primarily characterized by progressive cerebellar degeneration, including gray matter atrophy and disrupted anatomical and functional connectivity. The alterations of cerebellar white matter structural network in SCA3 and the underlying neurobiological mechanism remain unknown. Using a cohort of 20 patients with SCA3 and 20 healthy controls, we constructed cerebellar structural networks from diffusion MRI and investigated alterations of topological organization. Then, we mapped the alterations with transcriptome data from the Allen Human Brain Atlas to identify possible biological mechanisms for regional selective vulnerability to white matter damage. Compared with healthy controls, SCA3 patients exhibited reduced global and nodal efficiency, along with a widespread decrease in edge strength, particularly affecting edges connected to hub regions. The strength of inter-module connections was lower in SCA3 group and negatively correlated with the Scale for the Assessment and Rating of Ataxia score, International Cooperative Ataxia Rating Scale score, and cytosine-adenine-guanine repeat number. Moreover, the transcriptome-connectome association study identified the expression of genes involved in synapse-related and metabolic biological processes. These findings suggest a mechanism of white matter vulnerability and a potential image biomarker for the disease severity, providing insights into neurodegeneration and pathogenesis in this disease., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

An emerging trend is to use regression-based machine learning approaches to predict cognitive functions at the individual level from neuroimaging data. However, individual prediction models are inherently influenced by the vast options for network construction and model selection in machine learning pipelines. In particular, the brain white matter (WM) structural connectome lacks a systematic evaluation of the effects of different options in the pipeline on predictive performance. Here, we focused on the methodological evaluation of brain structural connectome-based predictions. For network construction, we considered two parcellation schemes for defining nodes and seven strategies for defining edges. For the regression algorithms, we used eight regression models. Four cognitive domains and brain age were targeted as predictive tasks based on two independent datasets (Beijing Aging Brain Rejuvenation Initiative [BABRI]: 633 healthy older adults; Human Connectome Projects in Aging [HCP-A]: 560 healthy older adults). Based on the results, the WM structural connectome provided a satisfying predictive ability for individual age and cognitive functions, especially for executive function and attention. Second, different parcellation schemes induce a significant difference in predictive performance. Third, prediction results from different data sets showed that dMRI with distinct acquisition parameters may plausibly result in a preference for proper fiber reconstruction algorithms and different weighting options. Finally, deep learning and Elastic-Net models are more accurate and robust in connectome-based predictions. Together, significant effects of different options in WM network construction and regression algorithms on the predictive performances are identified in this study, which may provide important references and guidelines to select suitable options for future studies in this field., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Previous studies have demonstrated that the brain functional modular organization, which is a fundamental feature of the human brain, would change along the adult lifespan. However, these studies assumed that each brain region belonged to a single functional module, although there has been convergent evidence supporting the existence of overlap among functional modules in the human brain. To reveal how age affects the overlapping functional modular organization, this study applied an overlapping module detection algorithm that requires no prior knowledge to the resting-state fMRI data of a healthy cohort (N = 570) aged from 18 to 88 years old. A series of measures were derived to delineate the characteristics of the overlapping modular structure and the set of overlapping nodes (brain regions participating in two or more modules) identified from each participant. Age-related regression analyses on these measures found linearly decreasing trends in the overlapping modularity and the modular similarity. The number of overlapping nodes was found increasing with age, but the increment was not even over the brain. In addition, across the adult lifespan and within each age group, the nodal overlapping probability consistently had positive correlations with both functional gradient and flexibility. Further, by correlation and mediation analyses, we showed that the influence of age on memory-related cognitive performance might be explained by the change in the overlapping functional modular organization. Together, our results revealed age-related decreased segregation from the brain functional overlapping modular organization perspective, which could provide new insight into the adult lifespan changes in brain function and the influence of such changes on cognitive performance., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Schizophrenia is a heterogenous psychiatric disease, and deficit schizophrenia (DS) is a clinical subgroup with primary and enduring negative symptoms. Although previous neuroimaging studies have identified functional connectome alterations in schizophrenia, the modular organizations in DS and nondeficit schizophrenia (NDS) remain poorly understood. Therefore, this study aimed to investigate the modular-level alterations in DS patients compared with the NDS and healthy control (HC) groups., Methods: A previously collected dataset was re-analyzed, in which 74 chronic male schizophrenia patients (33 DS and 41 NDS) and 40 HC underwent resting-state functional magnetic resonance imaging with eyes closed in a Siemens 3 T scanner (scanning duration = 8 min). Modular- (intramodule and intermodule connectivity) and nodal- [normalized within-module degree (Z i ) and participation coefficient (PC i )] level graph theory properties were computed and compared among the three groups. Receiver operating characteristic curve (ROC) analyses were performed to examine the classification ability of these measures, and partial correlations were conducted between network measures and symptom severity. Validation analyses on head motion, network sparsity, and parcellation scheme were also performed., Results: Both schizophrenia subgroups showed decreased intramodule connectivity in salience network (SN), somatosensory-motor network (SMN), and visual network (VN), and increased intermodule connectivity in SMN-default mode network (DMN) and SMN-frontoparietal network (FPN). Compared with NDS patients, DS patients showed weaker intramodule connectivity in SN and stronger intermodule connectivity in SMN-FPN and SMN-VN. At the nodal level, the schizophrenia-related alterations were distributed in SN, SMN, VN, and DMN, and 7 DS-specific nodal alterations were identified. Intramodule connectivity of SN, intermodule connectivity of SMN-VN, and Z i of left precuneus successfully distinguished the three groups. Partial correlational analyses revealed that these measures were related to negative symptoms, general psychiatric symptoms, and neurocognitive function., Conclusion: Our findings suggest that functional connectomes, especially SN, SMN, and VN, may capture the distinct and common disruptions of DS and NDS. These findings may help to understand the neuropathology of negative symptoms of schizophrenia and inform targets for treating different schizophrenia subtypes., (Copyright © 2021. Published by Elsevier Inc.)

It has been revealed that intersubject variability (ISV) in intrinsic functional connectivity (FC) is associated with a wide variety of cognitive and behavioral performances. However, the underlying organizational principle of ISV in FC and its related gene transcriptional profiles remain unclear. Using resting-state fMRI data from the Human Connectome Project (299 adult participants) and microarray gene expression data from the Allen Human Brain Atlas, we conducted a transcription-neuroimaging association study to investigate the spatial configurations of ISV in intrinsic FC and their associations with spatial gene transcriptional profiles. We found that the multimodal association cortices showed the greatest ISV in FC, while the unimodal cortices and subcortical areas showed the least ISV. Importantly, partial least squares regression analysis revealed that the transcriptional profiles of genes associated with human accelerated regions (HARs) could explain 31.29% of the variation in the spatial distribution of ISV in FC. The top-related genes in the transcriptional profiles were enriched for the development of the central nervous system, neurogenesis and the cellular components of synapse. Moreover, we observed that the effect of gene expression profile on the heterogeneous distribution of ISV in FC was significantly mediated by the cerebral blood flow configuration. These findings highlighted the spatial arrangement of ISV in FC and their coupling with variations in transcriptional profiles and cerebral blood flow supply., Competing Interests: Declaration of Competing Interest None, (Copyright © 2021. Published by Elsevier Inc.)

The frequency of brain activity modulates the relationship between the brain and human behavior. Insufficient understanding of frequency-specific features may thus lead to inconsistent explanations of human behavior. However, to date, the frequency-specific features of the human brain functional network at the whole-brain level remain poorly understood. Here, we used resting-state fMRI data and graph-theory analyses to investigate the frequency-specific characteristics of fMRI signals in 12 frequency bands (frequency range 0.01-0.7 Hz) in 75 healthy participants. We found that brain regions with higher level and more complex functions had a more variable functional connectivity pattern but engaged less in higher frequency ranges. Moreover, brain regions that engaged in fewer frequency bands played more integrated roles (i.e., higher network participation coefficient and lower within-module degree) in the functional network, whereas regions that engaged in broader frequency ranges exhibited more segregated functions (i.e., lower network participation coefficient and higher within-module degree). Finally, behavioral analyses revealed that regional frequency variability was associated with a spectrum of behavioral functions from sensorimotor functions to complex cognitive and social functions. Taken together, our results showed that segregated functions are executed in wide frequency ranges, whereas integrated functions are executed mainly in lower frequency ranges. These frequency-specific features of brain networks provided crucial insights into the frequency mechanism of fMRI signals, suggesting that signals in higher frequency ranges should be considered for their relation to cognitive functions.

Recently, functional connectome studies based on resting-state functional magnetic resonance imaging (R-fMRI) and graph theory have greatly advanced our understanding of the topological principles of healthy and diseased brains. However, how different strategies for R-fMRI data preprocessing and for connectome analyses jointly affect topological characterization and contrastive research of brain networks remains to be elucidated. Here, we used two R-fMRI data sets, a healthy young adult data set and an Alzheimer's disease (AD) patient data set, and up to 42 analysis strategies to comprehensively investigate the joint influence of three key factors (global signal regression, regional parcellation schemes, and null network models) on the topological analysis and contrastive research of whole-brain functional networks. At the global level, we first found that these three factors affected not only the quantitative values but also the individual variability profile in small-world related metrics and modularity, wherein global signal regression exhibited the predominant influence. Moreover, strategies without global signal regression and with topological randomization null model enhanced the sensitivity of the detection of differences between AD and control groups in small-worldness and modularity. At the nodal level, strategies of global signal regression dominantly influenced the spatial distribution of both hubs and between-group differences in terms of nodal degree centrality. Together, we highlight the remarkable joint influence of global signal regression, regional parcellation schemes and null network models on functional connectome analyses in both health and diseases, which may provide guidance for the choice of analysis strategies in future functional network studies., (© 2018 Wiley Periodicals, Inc.)

Deficit schizophrenia (DS), characterized by primary and enduring negative symptoms, has been considered as a pathophysiologically distinct schizophrenic subgroup. Neuroimaging characteristics of DS, especially functional brain network architecture, remain largely unknown. Resting-state functional magnetic resonance imaging and graph theory approaches were employed to investigate the topological organization of whole-brain functional networks of 114 male participants including 33 DS, 41 non-deficit schizophrenia (NDS) and 40 healthy controls (HCs). At the whole-brain level, both the NDS and DS group exhibited lower local efficiency (Eloc) than the HC group, implying the reduction of local specialization of brain information processing (reduced functional segregation). The DS, but not NDS group, exhibited enhanced parallel information transfer (enhanced functional integration) as determined by smaller characteristic path length (Lp) and higher global efficiency (Eglob). The Lp and Eglob presented significant correlations with Brief Psychiatric Rating Scale (BPRS) total score in the DS group. At the nodal level, both the NDS and DS groups showed higher functional connectivity in the inferior frontal gyrus and hippocampus, and lower connectivity in the visual areas and striatum than the controls. The DS group exhibited higher nodal connectivity in the right inferior temporal gyrus than the NDS and HC group. The diminished expression of Scale for the Assessment of Negative Symptoms (SANS) subfactors negatively correlated with nodal connectivity of right putamen, while asociality/amotivation positively correlated with right hippocampus across whole patients. We highlighted the convergence and divergence of brain functional network dysfunctions in patients with DS and NDS, which provides crucial insights into pathophysiological mechanisms of the 2 schizophrenic subtypes., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Alzheimer's disease (AD) is associated not only with regional gray matter damages, but also with abnormalities in functional integration between brain regions. Here, we employed resting-state functional magnetic resonance imaging data and voxel-based graph-theory analysis to systematically investigate intrinsic functional connectivity patterns of whole-brain networks in 32 AD patients and 38 healthy controls (HCs). We found that AD selectively targeted highly connected hub regions (in terms of nodal functional connectivity strength) of brain networks, involving the medial and lateral prefrontal and parietal cortices, insula, and thalamus. This impairment was connectivity distance-dependent (Euclidean), with the most prominent disruptions appearing in the long-range connections (e.g., 100-130 mm). Moreover, AD also disrupted functional connections within the default-mode, salience and executive-control modules, and connections between the salience and executive-control modules. These disruptions of hub connectivity and modular integrity significantly correlated with the patients' cognitive performance. Finally, the nodal connectivity strength in the posteromedial cortex exhibited a highly discriminative power in distinguishing individuals with AD from HCs. Taken together, our results emphasize AD-related degeneration of specific brain hubs, thus providing novel insights into the pathophysiological mechanisms of connectivity dysfunction in AD and suggesting the potential of using network hub connectivity as a diagnostic biomarker., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

For accurate diagnosis and prognostic prediction of acquired brain injury (ABI), it is crucial to understand the neurobiological mechanisms underlying loss of consciousness. However, there is no consensus on which regions and networks act as biomarkers for consciousness level and recovery outcome in ABI. Using resting-state fMRI, we assessed intrinsic functional connectivity strength (FCS) of whole-brain networks in a large sample of 99 ABI patients with varying degrees of consciousness loss (including fully preserved consciousness state, minimally conscious state, unresponsive wakefulness syndrome/vegetative state, and coma) and 34 healthy control subjects. Consciousness level was evaluated using the Glasgow Coma Scale and Coma Recovery Scale-Revised on the day of fMRI scanning; recovery outcome was assessed using the Glasgow Outcome Scale 3 months after the fMRI scanning. One-way ANOVA of FCS, Spearman correlation analyses between FCS and the consciousness level and recovery outcome, and FCS-based multivariate pattern analysis were performed. We found decreased FCS with loss of consciousness primarily distributed in the posterior cingulate cortex/precuneus (PCC/PCU), medial prefrontal cortex, and lateral parietal cortex. The FCS values of these regions were significantly correlated with consciousness level and recovery outcome. Multivariate support vector machine discrimination analysis revealed that the FCS patterns predicted whether patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%, and the most discriminative region was the PCC/PCU. These findings suggest that intrinsic functional connectivity patterns of the human posteromedial cortex could serve as a potential indicator for consciousness level and recovery outcome in individuals with ABI., Significance Statement: Varying degrees of consciousness loss and recovery are commonly observed in acquired brain injury patients, yet the underlying neurobiological mechanisms remain elusive. Using a large sample of patients with varying degrees of consciousness loss, we demonstrate that intrinsic functional connectivity strength in many brain regions, especially in the posterior cingulate cortex and precuneus, significantly correlated with consciousness level and recovery outcome. We further demonstrate that the functional connectivity pattern of these regions can predict patients with unresponsive wakefulness syndrome/vegetative state and coma would regain consciousness with an accuracy of 81.25%. Our study thus provides potentially important biomarkers of acquired brain injury in clinical diagnosis, prediction of recovery outcome, and decision making for treatment strategies for patients with severe loss of consciousness., (Copyright © 2015 the authors 0270-6474/15/3512933-15$15.00/0.)

Alzheimer's disease (AD) is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging (structural magnetic resonance imaging (MRI), diffusion MRI, and functional MRI) and neurophysiological techniques (electroencephalography and magnetoencephalography) with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment (MCI), the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks (i.e., connectomics) and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.

Abstract Studies have demonstrated that the clinical manifestations of Alzheimer's disease (AD) are associated with abnormal connections in either functional connectivity networks (FCNs) or structural connectivity networks (SCNs). However, the FCN and SCN of AD have usually been examined separately, and the results were inconsistent. In this multimodal study, we collected resting-state functional magnetic resonance imaging and diffusion magnetic resonance imaging data from 46 patients with AD and 39 matched healthy controls (HCs). Graph-theory analysis was used to investigate the topological organization of the FCN and SCN simultaneously. Compared with HCs, both the FCN and SCN of patients with AD showed disrupted network integration (i.e., increased characteristic path length) and segregation (i.e., decreased intramodular connections in the default mode network). Moreover, the FCN, but not the SCN, exhibited a reduced clustering coefficient and reduced rich club connections in AD. The coupling (i.e., correlation) of the FCN and SCN in AD was increased in connections of the default mode network and the rich club. These findings demonstrated overlapping and distinct network disruptions in the FCN and SCN and a strengthened correlation between FCNs and SCNs in AD, which provides a novel perspective for understanding the pathophysiological mechanisms underlying AD. Highlights • Disrupted topological organization in structural and functional networks of Alzheimer's disease (AD) • Disrupted clustering coefficient and rich club connections in AD functional networks • Correlation of functional and structural networks was increased in AD [ABSTRACT FROM AUTHOR]

Independent vs interdependent self-construal is a concept that reflects how people perceive the relationship between self and other people, which has been extensively examined across disciplines. However, little evidence on the whole-brain functional connectivity (FC) pattern of independent vs interdependent self-construal has been reported. Here, in a sample of 51 healthy participants, we used resting-state functional magnetic resonance imaging and voxel-based FC analysis (i.e. FC strength and seed-based FC) by measuring the temporal correlation of blood oxygen level-dependent signals between spatially separate brain regions to investigate the neural mechanism of independent vs interdependent self-construal. First, we found that FC strength of bilateral posterior cingulate cortex and precuneus, and left inferior frontal gyrus were positively correlated with the independent vs interdependent score. Seed-based FC analysis with these three regions as seeds revealed that, FC within default mode network and executive control network was positively correlated with the independent vs interdependent score. Negative correlation with independent vs interdependent score was shown in the connections between default mode network and executive control regions. Taking together, our results provide a comprehensive FC architecture of the independent vs interdependent self-construal and advance the understanding of the interplay between culture, mind and brain. [ABSTRACT FROM AUTHOR]

Relating the brain’s structural connectivity (SC) to its functional connectivity (FC) is a fundamental goal in neuroscience because it is capable of aiding our understanding of how the relatively fixed SC architecture underlies human cognition and diverse behaviors. With the aid of current noninvasive imaging technologies (e.g., structural MRI, diffusion MRI, and functional MRI) and graph theory methods, researchers have modeled the human brain as a complex network of interacting neuronal elements and characterized the underlying structural and functional connectivity patterns that support diverse cognitive functions. Specifically, research has demonstrated a tight SC-FC coupling, not only in interregional connectivity strength but also in network topologic organizations, such as community, rich-club, and motifs. Moreover, this SC-FC coupling exhibits significant changes in normal development and neuropsychiatric disorders, such as schizophrenia and epilepsy. This review summarizes recent progress regarding the SC-FC relationship of the human brain and emphasizes the important role of large-scale brain networks in the understanding of structural-functional associations. Future research directions related to this topic are also proposed. [ABSTRACT FROM AUTHOR]

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole-brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting-state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole-brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph-theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal-limbic-thalamic-cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole-brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp 35:1154-1166, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Neuroimaging studies have demonstrated that patients with Alzheimer's disease (AD) have remarkable focal grey matter loss and hypometabolism in the posteromedial cortex (PMC), which is composed of the precuneus and posterior cingulate cortex, suggesting an important association of the PMC with AD pathophysiology. Studies have also shown that the PMC is a structurally and functionally heterogeneous structure containing various subregions with distinct connectivity profiles. However, whether these PMC subregions show differentially disrupted connectivity patterns in AD remains largely unknown. Here, we addressed this issue by collecting resting-state functional MRI data from 32 AD patients and 38 healthy controls. We automatically identified the PMC subregions using a graph-based module detection algorithm and then mapped the whole-brain functional connectivity pattern of each subregion. The functional connectivity analysis was followed by a hierarchical clustering analysis to classify each subregion. Three distinct spatial connectivity patterns were observed across the PMC subregions: the anterior dorsal zone was functionally connected with the sensorimotor cortex; the posterior dorsal zone was functionally connected with the frontoparietal cortex; and the central and ventral zones were functionally connected with the default-mode regions. Group comparison analysis revealed that all three functional systems were significantly disrupted in the AD patients compared to the controls and these disruptions were positively correlated with the patients' cognitive performance. Collectively, we showed that the subregions of the PMC exhibit differentially disrupted neuronal circuitry in AD patients, which provides new insight into the functional neuroanatomy of the human PMC and the alterations that may be relevant to disease. [ABSTRACT FROM AUTHOR]

Abstract: Increasing attention has recently been directed to the applications of pattern recognition and brain imaging techniques in the effective and accurate diagnosis of Alzheimer''s disease (AD). However, most of the existing research focuses on the use of single-modal (e.g., structural or functional MRI) or single-level (e.g., brain local or connectivity metrics) biomarkers for the diagnosis of AD. In this study, we propose a methodological framework, called multi-modal imaging and multi-level characteristics with multi-classifier (M3), to discriminate patients with AD from healthy controls. This approach involved data analysis from two imaging modalities: structural MRI, which was used to measure regional gray matter volume, and resting-state functional MRI, which was used to measure three different levels of functional characteristics, including the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and regional functional connectivity strength (RFCS). For each metric, we computed the values of ninety regions of interest derived from a prior atlas, which were then further trained using a multi-classifier based on four maximum uncertainty linear discriminant analysis base classifiers. The performance of this method was evaluated using leave-one-out cross-validation. Applying the M3 approach to the dataset containing 16 AD patients and 22 healthy controls led to a classification accuracy of 89.47% with a sensitivity of 87.50% and a specificity of 90.91%. Further analysis revealed that the most discriminative features for classification are predominantly involved in several default-mode (medial frontal gyrus, posterior cingulate gyrus, hippocampus and parahippocampal gyrus), occipital (fusiform gyrus, inferior and middle occipital gyrus) and subcortical (amygdale and pallidum of lenticular nucleus) regions. Thus, the M3 method shows promising classification performance by incorporating information from different imaging modalities and different functional properties, and it has the potential to improve the clinical diagnosis and treatment evaluation of AD. [Copyright &y& Elsevier]

It is widely believed that the formation of brain network architecture is under the pressure of optimal trade-off between reducing wiring cost and promoting communication efficiency. However, the questions of whether this trade-off exists in empirical human brain structural networks and, if so, how it takes effect are still not well understood. Here, we employed a multiobjective evolutionary algorithm to directly and quantitatively explore the cost-efficiency trade-off in human brain structural networks. Using this algorithm, we generated a population of synthetic networks with optimal but diverse cost-efficiency trade-offs. It was found that these synthetic networks could not only reproduce a large portion of connections in the empirical brain structural networks but also embed a resembling small-world organization. Moreover, the synthetic and empirical brain networks were found similar in terms of the spatial arrangement of hub regions and the modular structure, which are two important topological features widely assumed to be outcomes of cost-efficiency trade-offs. The synthetic networks had high robustness against random attacks as the empirical brain networks did. Additionally, we also revealed some differences between the synthetic networks and the empirical brain networks, including lower segregated processing capacity and weaker robustness against targeted attacks in the synthetic networks. These findings provide direct and quantitative evidence that the structure of human brain networks is indeed largely influenced by optimal cost-efficiency trade-offs. We also suggest that some additional factors (e.g., segregated processing capacity) might jointly determine the network organization with cost and efficiency. [ABSTRACT FROM AUTHOR]