Rich Club Nodes Research Articles

Rich-club organization of whole-brain spatio-temporal multilayer functional connectivity networks

ObjectiveIn this work, we propose a novel method for constructing whole-brain spatio-temporal multilayer functional connectivity networks (FCNs) and four innovative rich-club metrics.MethodsSpatio-temporal multilayer FCNs achieve a high-order representation of the spatio-temporal dynamic characteristics of brain networks by combining the sliding time window method with graph theory and hypergraph theory. The four proposed rich-club scales are based on the dynamic changes in rich-club node identity, providing a parameterized description of the topological dynamic characteristics of brain networks from both temporal and spatial perspectives. The proposed method was validated in three independent differential analysis experiments: male–female gender difference analysis, analysis of abnormality in patients with autism spectrum disorders (ASD), and individual difference analysis.ResultsThe proposed method yielded results consistent with previous relevant studies and revealed some innovative findings. For instance, the dynamic topological characteristics of specific white matter regions effectively reflected individual differences. The increased abnormality in internal functional connectivity within the basal ganglia may be a contributing factor to the occurrence of repetitive or restrictive behaviors in ASD patients.ConclusionThe proposed methodology provides an efficacious approach for constructing whole-brain spatio-temporal multilayer FCNs and conducting analysis of their dynamic topological structures. The dynamic topological characteristics of spatio-temporal multilayer FCNs may offer new insights into physiological variations and pathological abnormalities in neuroscience.

P300 intention recognition based on phase lag index (PLI)-rich-club brain functional network.

Brain-computer interface (BCI) technology based on P300 signals has a broad application prospect in the assessment and diagnosis of clinical diseases and game control. The paper of selecting key electrodes to realize a wearable intention recognition system has become a hotspot for scholars at home and abroad. In this paper, based on the rich-club phenomenon that exists in the process of intention generation, a phase lag index (PLI)-rich-club-based intention recognition method for P300 is proposed. The rich-club structure is a network consisting of electrodes that are highly connected with other electrodes in the process of P300 generation. To construct the rich-club network, this paper uses PLI to construct the brain functional network, calculates rich-club coefficients of the network in the range of k degrees, initially identifies rich-club nodes based on the feature of node degree, and then performs a descending order of betweenness centrality and identifies the nodes with larger betweenness centrality as the specific rich-club nodes, extracts the non-linear features and frequency domain features of Rich-club nodes, and finally uses support vector machine for classification. The experimental results show that the range of rich-club coefficients is smaller with intent compared to that without intent. Validation was performed on the BCI Competition III dataset by reducing the number of channels to 17 and 16 for subject A and subject B, with recognition quasi-departure rates of 96.93% and 94.93%, respectively, and on the BCI Competition II dataset by reducing the number of channels to 17 for subjects, with a recognition accuracy of 95.50%.

Increasing variance of rich-club nodes distribution in early onset depression according to dynamic network.

Early onset depression (EOD) and late onset depression (LOD) are thought to have different pathogeneses, but lack of pathological evidence. In the current study we describe the dynamic rich-club properties of patients with EOD and LOD to address this question indirectly. We recruited 82 patients with late life depression (EOD 40, LOD 42) and 90 healthy controls. Memory, executive function and processing speed were measured, and resting-stage functional MRI was performed with all participants. We constructed a dynamic functional connectivity network and carried out rich-club and modularity analyses. Normalized mutual information (NMI) was applied to describe the variance in rich-club nodes distribution and partitioning. The NMI coefficient of rich club nodes distribution among the three groups was the lowest in the EOD patients (F = 4.298; P = 0.0151, FDR = 0.0231), which was positively correlated with rich-club connectivity (R = 0.886, P < 0.001) and negatively correlated with memory (R = -0.347, P = 0.038) in the EOD group. In the LOD patients, non-rich-club connectivity was positively correlated with memory (R = 0.353, P = 0.030 and R = 0.420, P = 0.009). Furthermore, local connectivity was positively correlated with processing speed in the LOD patients (R = 0.374, P = 0.021). The modular partition was different between the EOD patients and the HCs (P = 0.0013 < 0.05/3). The temporal instability of rich-club nodes was found in the EOD patients, but not the LOD patients, supporting the hypothesis that EOD and LOD result from different pathogenesis, and showing that the instability of the rich-club nodes across time might disrupt rich-club connectivity.

Exploration of rich-club reorganization in facial synkinesis: insights from structural and functional brain network analysis.

Facial palsy therapies based on cortical plasticity are in development, but facial synkinesis progress is limited. Studying neural plasticity characteristics, especially network organization and its constitutive elements (nodes/edges), is the key to overcome the bottleneck. We studied 55 participants (33 facial synkinesis patients, 22 healthy controls) with clinical assessments, functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI). We analyzed rich-club organization and metrics of structural brain networks (rich-club coefficients, strength, degree, density, and efficiency). Functional brain network metrics, including functional connectivity and its coupling with the structural network, were also computed. Patients displayed reduced strength and density of rich-club nodes and edges, as well as decreased global efficiency. All nodes exhibited decreased nodal efficiency in patients. Patients had significantly increased functional connectivity and decreased structural-functional coupling strength in rich-club nodes, rich-club edges, and feeder edges. Our study indicates that facial synkinesis patients have weakened structural connections but enhanced functional transmission from rich-club nodes. The loss of connections and efficiency in structural network may trigger compensatory increases in functional connectivity of rich-club nodes. Two potential biomarkers, rich-club edge density and structural-functional coupling strength, may serve as indicators of disease outcome. These findings provide valuable insights into synkinesis mechanisms and offer potential targets for cortical intervention.

Altered brain structural and functional connectivity in cannabis users

Cannabis is one of the most used and commodified illicit substances worldwide, especially among young adults. The neurobiology mechanism of cannabis is yet to be identified particularly in youth. The purpose of this study was to concurrently measure alterations in brain structural and functional connectivity in cannabis users using resting-state functional magnetic resonance images (rs-fMRI) and diffusion-weighted images (DWI) from a group of 73 cannabis users (age 22–36, 19 female) in comparison with 73 healthy controls (age 22–36, 14 female) from Human Connectome Project (HCP). Several significant differences were observed in local structural/functional network measures (e.g. degree and clustering coefficient), being prominent in the insular and frontal opercular cortex and lateral/medial temporal cortex. The rich-club organization of structural networks revealed a normal trend, distributed within bilateral frontal, temporal and occipital regions. However, minor differences were found between the two groups in the superior and inferior temporal gyri. Functional rich-club nodes were mostly located within parietal and posterior areas, with minor differences between the groups found mainly in the centro-temporal and parietal regions. Regional network measures of structural/functional networks were associated with times used cannabis (TUC) in several regions. Although the structural/functional network in both groups showed small-world property, no differences between cannabis users and healthy controls were found regarding the global network measures, showing no association with cannabis use. After FDR correction, all of the significant associations between network measures and TUC were found to be insignificant, except for the association between degree and TUC within the presubiculum region. To recap, our findings revealed alterations in local topological properties of structural and functional networks in cannabis users, although their global brain network organization remained intact.

Iron deposition in the precuneus is correlated with mild cognitive impairment in patients with cerebral microbleeds: A quantitative susceptibility mapping study.

PurposeThe purpose of this study was to define whether mild cognitive impairment (MCI) is associated with iron deposition in rich-club nodes distant from cerebral microbleeds (CMBs) in patients with cerebral small vessel disease (CSVD).MethodsA total of 64 participants underwent magnetic resonance imaging (MRI) scanning and were separated into three groups, namely, CMB(+), CMB(–), and healthy controls (HCs). We compared their characteristics and susceptibility values of rich-club nodes [e.g., superior frontal gyrus (SFG), precuneus, superior occipital gyrus (SOG), thalamus, and putamen]. We then divided the CMB(+) and CMB(–) groups into subgroups of patients with or without MCI. Then, we analyzed the relationship between iron deposition and MCI by comparing the susceptibility values of rich-club nodes. We assessed cognitive functions using the Montreal Cognitive Assessment (MoCA) and quantified iron content using quantitative susceptibility mapping (QSM).ResultsIn the putamen, the CMB(+) and CMB(–) groups had significantly different susceptibility values. Compared with the HCs, the CMB(+) and CMB(–) groups had significantly different susceptibility values for the SFG and SOG. In addition, we found significant differences in the putamen susceptibility values of the CMB(+)MCI(+) group and the two CMB(–) groups. The CMB(+)MCI(+) and CMB(+)MCI(–) groups had significantly different precuneus susceptibility values. The binary logistic regression analysis revealed that only higher susceptibility values of precuneus were associated with a cognitive decline in patients with CMBs, and it indicated statistical significance.ConclusionIron deposition in the precuneus is an independent risk factor for MCI in patients with CMBs. CMBs might influence iron content in remote rich-club nodes and be relevant to MCI.

Normalization effect of levodopa on hierarchical brain function in Parkinson's disease.

Hierarchical brain organization, in which the rich club and diverse club situate in core position, is critical for global information integration in the human brain network. Parkinson’s disease (PD), a common movement disorder, has been conceptualized as a network disorder. Levodopa is an effective treatment for PD. Whether there is a functional divergence in the hierarchical brain system under PD pathology, and how this divergence is regulated by immediate levodopa therapy, remains unknown. We constructed a functional network in 61 PD patients and 89 normal controls and applied graph theoretical analyses to examine the neural mechanism of levodopa short response from the perspective of brain hierarchical configuration. The results revealed the following: (a) PD patients exhibited disrupted function within rich-club organization, while the diverse club preserved function, indicating a differentiated brain topological organization in PD. (b) Along the rich-club derivate hierarchical system, PD patients showed impaired network properties within rich-club and feeder subnetworks, and decreased nodal degree centrality in rich-club and feeder nodes, along with increased nodal degree in peripheral nodes, suggesting distinct functional patterns in different types of nodes. And (c) levodopa could normalize the abnormal network architecture of the rich-club system. This study provides evidence for levodopa effects on the hierarchical brain system with divergent functions.

Reorganized Brain Functional Network Topology in Presbycusis.

PurposePresbycusis is characterized by bilateral sensorineural hearing loss at high frequencies and is often accompanied by cognitive decline. This study aimed to identify the topological reorganization of brain functional network in presbycusis with/without cognitive decline by using graph theory analysis approaches based on resting-state functional magnetic resonance imaging (rs-fMRI).MethodsResting-state fMRI scans were obtained from 30 presbycusis patients with cognitive decline, 30 presbycusis patients without cognitive decline, and 50 age-, sex-, and education-matched healthy controls. Graph theory was applied to analyze the topological properties of brain functional networks including global and nodal metrics, modularity, and rich-club organization.ResultsAt the global level, the brain functional networks of all participants were found to possess small-world properties. Also, significant group differences in global network metrics were observed among the three groups such as clustering coefficient, characteristic path length, normalized characteristic path length, and small-worldness. At the nodal level, several nodes with abnormal betweenness centrality, degree centrality, nodal efficiency, and nodal local efficiency were detected in presbycusis patients with/without cognitive decline. Changes in intra-modular connections in frontal lobe module and inter-modular connections in prefrontal subcortical lobe module were found in presbycusis patients exposed to modularity analysis. Rich-club nodes were reorganized in presbycusis patients, while the connections among them had no significant group differences.ConclusionPresbycusis patients exhibited topological reorganization of the whole-brain functional network, and presbycusis patients with cognitive decline showed more obvious changes in these topological properties than those without cognitive decline. Abnormal changes of these properties in presbycusis patients may compensate for cognitive impairment by mobilizing additional neural resources.

Strengthened and posterior-shifted structural rich-club organization in people who use cocaine

BackgroundPeople with cocaine use disorder (CUD) often have abnormal cognitive function and brain structure. Cognition is supported by brain networks that typically have characteristics like rich-club organization, which is a group of regions that are highly connected across the brain and to each other, and small worldness, which is a balance between local and long-distance connections. However, it is unknown whether there are abnormalities in structural brain network connectivity of CUD. MethodsUsing diffusion-weighted imaging, we measured structural connectivity in 37 people with CUD and 38 age-matched controls. We identified differences in rich-club organization and whether such differences related to small worldness and behavior. We also tested whether rich-club reorganization was associated with caudate and putamen structural connectivity due to the relevance of the dopamine system to cocaine use. ResultsPeople with CUD had a higher normalized rich-club coefficient than controls, more edges connecting rich-club nodes to each other and to non-rich-club nodes, and fewer edges connecting non-rich-club nodes. Rich-club nodes were shifted posterior and lateral. Rich-club reorganization was related to lower clustered connectivity around individual nodes found in CUD, to increased impulsivity, and to a decrease in caudate connectivity. ConclusionsThese findings are consistent with previous work showing increased rich-club connectivity in conditions associated with a hypofunctional dopamine system. The posterior shift in rich-club nodes in CUD suggests that the structural connectivity of posterior regions may be more impacted than previously recognized in models based on brain function and morphology.

Reorganization of rich clubs in functional brain networks of dementia with Lewy bodies and Alzheimer’s disease

The purpose of this study was to reveal the patterns of reorganization of rich club organization in brain functional networks in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The study found that the rich club node shifts from sensory/somatomotor network to fronto-parietal network in DLB. For AD, the rich club nodes switch between the temporal lobe with obvious structural atrophy and the frontal lobe, parietal lobe and cerebellum with relatively preserved structure and function. In addition, compared with healthy controls, rich club connectivity was enhanced in the DLB and AD groups. The connection strength of DLB patients was related to cognitive assessment. In conclusion, we revealed the different functional reorganization patterns of DLB and AD. The conversion and redistribution of rich club members may play a causal role in disease-specific outcomes. It may be used as a potential biomarker to provide more accurate prevention and treatment strategies.

Topological features of limbic dysfunction in chronicity of tinnitus with intact hearing: New hypothesis for ‘noise-cancellation’ mechanism

PurposeThe reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular ‘hubs’ contributing to a ‘noise-cancellation’ mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods. MethodsResting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis. ResultsCommon small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p < 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus. ConclusionsBrain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in ‘noise-cancellation’ mechanism.

Multi-scale structural rich-club organization of the brain in full-term newborns: a combined DWI and fMRI study

Objective. Our understanding of early brain development is limited due to rapid changes in white matter pathways after birth. In this study, we introduced a multi-scale cross-modal approach to investigate the rich club (RC) organization and topology of the structural brain networks in 40 healthy neonates using diffusion-weighted imaging and resting-state fMRI data. Approach. A group independent component analysis was first performed to identify eight resting state networks (RSNs) used as functional modules. A groupwise whole-brain functional parcellation was also performed at five scales comprising 100–900 parcels. The distribution of RC nodes was then investigated within and between the RSNs. We further assessed the distribution of short and long-range RC, feeder and local connections across different parcellation scales. Main results. Sharing the scale-free characteristic of small-worldness, the neonatal structural brain networks exhibited an RC organization at different nodal scales (NSs). The subcortical, sensory-motor and default mode networks were found to be strongly involved in the RC organization of the structural brain networks, especially in the zones where the RSNs overlapped, with an average cross-scale proportion of 45.9%, 28.5% and 10.5%, respectively. A large proportion of the connector hubs were found to be RC members for the coarsest (73%) to finest (92%) NSs. Our results revealed a prominent involvement of cortico-subcortical and cortico-cerebellar white matter pathways in the RC organization of the neonatal brain. Regardless of the NS, the majority (more than 65.2%) of the inter-RSN connections were long distance RC or feeder with an average physical connection of 105.5 and 97.4 mm, respectively. Several key RC regions were identified, including the insula and cingulate gyri, middle and superior temporal gyri, hippocampus and parahippocampus, fusiform gyrus, precuneus, superior frontal and precentral gyri, calcarine fissure and lingual gyrus. Significance. Our results emphasize the importance of the multi-scale connectivity analysis in assessing the cross-scale reproducibility of the connectivity results concerning the global and local topological properties of the brain networks. Our findings may improve our understanding of the early brain development.

Disruption of Rich-Club Connectivity in Cushing Disease

Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD.

Sex Differences in Anatomical Rich-Club and Structural-Functional Coupling in the Human Brain Network.

Structural and functional differences between the brains of female and male adults have been well documented. However, potential sex differences in the patterns of rich-club organization and the coupling between their structural connectivity (SC) and functional connectivity (FC) remain to be determined. In this study, functional magnetic resonance imaging and diffusion tensor imaging techniques were combined to examine sex differences in rich-club organization. Females had a stronger SC-FC coupling than males. Moreover, stronger SC-FC coupling in the females was primarily located in feeder connections and non-rich-club nodes of the left inferior frontal gyrus and inferior parietal lobe and the right superior frontal gyrus and superior parietal gyrus, whereas higher coupling strength in males was primarily located in rich-club connections and rich-club node of the right insula, and non-rich-club nodes of the left hippocampus and the right parahippocampal gyrus. Sex-specific patterns in correlations were also shown between SC-FC coupling and cognitive function, including working memory and reasoning ability. The topological changes in rich-club organization provide novel insight into sex-specific effects on white matter connections that underlie a potential network mechanism of sex-based differences in cognitive function.

Altered Rich-Club Organization and Regional Topology Are Associated With Cognitive Decline in Patients With Frontal and Temporal Gliomas.

ObjectivesGliomas are widely considered to be related to the altered topological organization of functional networks before operations. Tumors are usually thought to cause multimodal cognitive impairments. The structure is thought to form the basics of function, and the aim of this study was to reveal the rich-club organization and topological patterns of white matter (WM) structural networks associated with cognitive impairments in patients with frontal and temporal gliomas.MethodsGraph theory approaches were utilized to reveal the global and regional topological organization and rich-club organization of WM structural networks of 14 controls (CN), 13 frontal tumors (FTumor), and 18 temporal tumors (TTumor). Linear regression was used to assess the relationship between cognitive performances and altered topological parameters.ResultsWhen compared with CN, both FTumor and TTumor showed no alterations in small-world properties and global network efficiency, but instead showed altered local network efficiency. Second, FTumor and TTumor patients showed similar deficits in the nodal shortest path in the left rolandic operculum and degree centrality (DC) of the right dorsolateral and medial superior frontal gyrus (SFGmed). Third, compared to FTumor patients, TTumor patients showed a significantly higher DC in the right dorsolateral and SFGmed, a higher level of betweenness in the right SFGmed, and higher nodal efficiency in the left middle frontal gyrus and right SFGmed. Finally, rich-club organization was disrupted, with increased structural connectivity among rich-club nodes and reduced structural connectivity among peripheral nodes in FTumor and TTumor patients. Altered local efficiency in TTumor correlated with memory function, while altered local efficiency in FTumor correlated with the information processing speed.ConclusionBoth FTumor and TTumor presented an intact global topology and altered regional topology related to cognitive impairment and may also share the convergent and divergent regional topological organization of WM structural networks. This suggested that a compensatory mechanism plays a key role in global topology formation in both FTumor and TTumor patients, and as such, development of a structural connectome for patients with brain tumors would be an invaluable medical resource and allow clinicians to make comprehensive preoperative planning.

Reorganization of rich-clubs in functional brain networks during propofol-induced unconsciousness and natural sleep.

General anesthesia (GA) provides an invaluable experimental tool to understand the essential neural mechanisms underlying consciousness. Previous neuroimaging studies have shown the functional integration and segregation of brain functional networks during anesthetic-induced alteration of consciousness. However, the organization pattern of hubs in functional brain networks remains unclear. Moreover, comparisons with the well-characterized physiological unconsciousness can help us understand the neural mechanisms of anesthetic-induced unconsciousness. Resting-state functional magnetic resonance imaging was performed during wakefulness, mild propofol-induced sedation (m-PIS), and deep PIS (d-PIS) with clinical unconsciousness on 8 healthy volunteers and wakefulness and natural sleep on 9 age- and sex-matched healthy volunteers. Large-scale functional brain networks of each volunteer were constructed based on 160 regions of interest. Then, rich-club organizations in brain functional networks and nodal properties (nodal strength and efficiency) were assessed and analyzed among the different states and groups. Rich-clubs in the functional brain networks were reorganized during alteration of consciousness induced by propofol. Firstly, rich-club nodes were switched from the posterior cingulate cortex (PCC), angular gyrus, and anterior and middle insula to the inferior parietal lobule (IPL), inferior parietal sulcus (IPS), and cerebellum. When sedation was deepened to unconsciousness, the rich-club nodes were switched to the occipital and angular gyrus. These results suggest that the rich-club nodes were switched among the high-order cognitive function networks (default mode network [DMN] and fronto-parietal network [FPN]), sensory networks (occipital network [ON]), and cerebellum network (CN) from consciousness (wakefulness) to propofol-induced unconsciousness. At the same time, compared with wakefulness, local connections were switched to rich-club connections during propofol-induced unconsciousness, suggesting a strengthening of the overall information commutation of networks. Nodal efficiency of the anterior and middle insula and ventral frontal cortex was significantly decreased. Additionally, from wakefulness to natural sleep, a similar pattern of rich-club reorganization with propofol-induced unconsciousness was observed: rich-club nodes were switched from the DMN (including precuneus and PCC) to the sensorimotor network (SMN, including part of the frontal and temporal gyrus). Compared with natural sleep, nodal efficiency of the insula, frontal gyrus, PCC, and cerebellum significantly decreased during propofol-induced unconsciousness. Our study demonstrated that the rich-club reorganization in functional brain networks is characterized by switching of rich-club nodes between the high-order cognitive and sensory and motor networks during propofol-induced alteration of consciousness and natural sleep. These findings will help understand the common neurological mechanism of pharmacological and physiological unconsciousness.

Topological reorganization of brain functional networks in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes

Mitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the topological organization of brain functional network in MELAS has not been explored. Here, 45 patients with MELAS (22 at acute stage, 23 at chronic stage) and 22 normal controls were studied using resting- state functional magnetic resonance imaging and graph theory analysis approaches. Topological properties of brain functional networks including global and nodal metrics, rich club organization and modularity were analyzed. At the global level, MELAS patients exhibited reduced clustering coefficient, normalized clustering coefficient, normalized characteristic path length and local network efficiency compared with the controls. At the nodal level, several nodes with abnormal degree centrality and nodal efficiency were detected in MELAS patients, and the distribution of these nodes was partly consistent with the stroke-like lesions. For rich club organization, rich club nodes were reorganized and the connections among them were decreased in MELAS patients. Modularity analysis revealed that MELAS patents had altered intra- or inter-modular connections in default mode network, fronto-parietal network, sensorimotor network, occipital network and cerebellum network. Notably, the patients at acute stage showed more obvious changes in these topological properties than the patients at chronic stage. These findings indicated that MELAS patients, particularly those at acute stage, exhibited topological reorganization of the whole-brain functional network. This study may help us to understand the neuropathological mechanisms of MELAS.

Rich-Club Organization: An Important Determinant of Functional Outcome After Acute Ischemic Stroke.

Objective: To determine whether the rich-club organization, essential for information transport in the human connectome, is an important biomarker of functional outcome after acute ischemic stroke (AIS).Methods: Consecutive AIS patients (N = 344) with acute brain magnetic resonance imaging (MRI) (<48 h) were eligible for this study. Each patient underwent a clinical MRI protocol, which included diffusion weighted imaging (DWI). All DWIs were registered to a template on which rich-club regions have been defined. Using manual outlines of stroke lesions, we automatically counted the number of affected rich-club regions and assessed its effect on the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS; obtained at 90 days post-stroke) scores through ordinal regression.Results: Of 344 patients (median age 65, inter-quartile range 54–76 years) with a median DWI lesion volume (DWIv) of 3cc, 64% were male. We established that an increase in number of rich-club regions affected by a stroke increases the odds of poor stroke outcome, measured by NIHSS (OR: 1.77, 95%CI 1.41–2.21) and mRS (OR: 1.38, 95%CI 1.11–1.73). Additionally, we demonstrated that the OR exceeds traditional markers, such as DWIv (ORNIHSS 1.08, 95%CI 1.06–1.11; ORmRS 1.05, 95%CI 1.03–1.07) and age (ORNIHSS 1.03, 95%CI 1.01–1.05; ORmRS 1.05, 95%CI 1.03–1.07).Conclusion: In this proof-of-concept study, the number of rich-club nodes affected by a stroke lesion presents a translational biomarker of stroke outcome, which can be readily assessed using standard clinical AIS imaging protocols and considered in functional outcome prediction models beyond traditional factors.

Rehabilitative compensatory mechanism of hierarchical subnetworks in major depressive disorder: A longitudinal study across multi-sites

BackgroundBrain structural connectome comprise of a minority of efficiently interconnected rich club nodes that are regarded as ‘high-order regions’. The remission of major depressive disorder (MDD) in response to selective serotonin reuptake inhibitor (SSRI) treatment could be investigated by the hierarchical structural connectomes’ alterations of subnetworks. MethodsFifty-five MDD patients who achieved remission underwent diffusion tensors imaging (DTI) scanning from 3 cohorts before and after 8-weeks antidepressant treatment. Five hierarchical subnetworks namely, rich, local, feeder, rich-feeder and feeder-local, were constructed according to the different combinations of connections and nodes as defined by rich club architecture. The critical treatment-related subnetwork pattern was explored by multivariate pattern analysis with support vector machine to differ the pre-/post-treatment patients. Then, relationships between graph metrics of discriminative subnetworks/ nodes and clinical variables were further explored. ResultsThe feeder-local subnetwork presented the most discriminative power in differing pre-/post- treatment patients, while the rich-feeder subnetwork had the highest discriminative power when comparing pre-treatment patients and controls. Furthermore, based on the feeder connection, which indicates the information transmission between the core and non-core architectures of brain networks, its topological measures were found to be significantly correlated with the reduction rate of 17-item Hamilton Rating Scale for Depression. ConclusionAlthough pathological lesion on MDD relied on abnormal core organization, disease remission was association with the compensation from non-core organization. These results suggested that the dysfunctions arising from hierarchical subnetworks are compensated by increased information interactions between core brain regions and functionally diverse regions.

Persistent changes in cortical, subcortical and network-level dynamics induced by 10-Hz tACS applied over bilateral parietal cortex: a MEG study

Previous studies of the effects of tACS on brain dynamics report entrainment at the stimulation frequency, modulation of phase-phase and phase-amplitude relationships, and non-linear effects such as the generation of harmonic and subharmonic oscillatory activity. The majority of these investigations characterized the on-line effects of tACS in regions proximal to the stimulation electrodes. We utilized a 306-channel MEG array to characterize persistent changes in brain dynamics induced by alpha-band tACS. Eight adults with no neurological or mental disorders received 10-Hz stimulation over bilateral parietal cortex (EEG sites P3/P4; 1 mA; 20 min verum, 30 s sham). Participants performed a global/local visual attention task during and after stimulation. Spectro-temporal (TF) and spectral Granger causality measures were utilized to characterize changes in brain dynamics for cortical and subcortical nodes in the Default Mode Network (DMN) and Rich Club. Although there were frequency-, epoch- and task-related effects, verum vs. sham stimulation tended to upregulate gamma-band activity in the DMN nodes of left middle temporal and inferior parietal cortex, bilateral lateral occipital and medial orbitofrontal and bilateral crus I/II of cerebellum. Downregulation occurred primarily in the Rich Club nodes of right precuneus and right superior frontal cortex. There was little evidence for down-regulation within superior parietal cortex and hippocampus. A spectral Granger causality analysis revealed a complex dependence on brain region and task. Interestingly, all significant changes observed at 10, 20, 30, 40 and 70 Hz were consistently either increases or decreases in causality between ordered pairs of nodes. Causality was increased (decreased) following tACS for posterior cortical nodes in the DNM (Rich Club) networks. In contrast, posterior-to-frontal causal relationships increased for nodes in both networks. Changes in cortico-cerebellar relationships occurred only during attention to local features of visual images. The influence of hippocampus onto cortical nodes decreased for both tasks.