Multimodal imaging investigation of structural rich club alterations in Alzheimer's disease and mild cognitive impairment: Amyloid deposition, structural atrophy, and functional activation differences.

Alzheimer's disease (AD) is characterized by significant cerebral dysfunction, including increased amyloid deposition, gray matter atrophy, and changes in brain function. The involvement of highly connected network hubs, known as the "rich club," in the pathology of the disease remains inconclusive despite previous research efforts. In this study, we aimed to systematically assess the link between the rich club and AD using a multimodal neuroimaging approach. We employed network analyses of diffusion magnetic resonance imaging (MRI), longitudinal assessments of gray matter atrophy, amyloid deposition measurements using positron emission tomography (PET) imaging, and meta-analytic data on functional activation differences. Our study focused on evaluating the role of both the structural brain network's core and extended rich club regions in individuals with mild cognitive impairment (MCI) and those diagnosed with AD. Our findings revealed that structural rich club regions exhibited accelerated gray matter atrophy and increased amyloid deposition in both MCI and AD. Importantly, these regions remained unaffected by altered functional activation patterns observed outside the core rich club regions. These results shed light on the connection between two major AD biomarkers and the rich club, providing valuable insights into AD as a potential disconnection syndrome.

The significance of structural rich club hubs for the processing of hierarchical stimuli.

The brain's structural network follows a hierarchy that is described as rich club (RC) organization, with RC hubs forming the well-interconnected top of this hierarchy. In this study, we tested whether RC hubs are involved in the processing of hierarchically higher structures in stimulus sequences. Moreover, we explored the role of previously suggested cortical gradients along anterior-posterior and medial-lateral axes throughout the frontal cortex. To this end, we conducted a functional magnetic resonance imaging (fMRI) experiment and presented participants with blocks of digit sequences that were structured on different hierarchically nested levels. We additionally collected diffusion weighted imaging data of the same subjects to identify RC hubs. This classification then served as the basis for a region of interest analysis of the fMRI data. Moreover, we determined structural network centrality measures in areas that were found as activation clusters in the whole-brain fMRI analysis. Our findings support the previously found anterior and medial shift for processing hierarchically higher structures of stimuli. Additionally, we found that the processing of hierarchically higher structures of the stimulus structure engages RC hubs more than for lower levels. Areas involved in the functional processing of hierarchically higher structures were also more likely to be part of the structural RC and were furthermore more central to the structural network. In summary, our results highlight the potential role of the structural RC organization in shaping the cortical processing hierarchy.

Disrupted pattern of rich-club organization in structural brain network from prediabetes to diabetes: A population-based study.

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.

Rich Club Reorganization in Nurses Before and After the Onset of Occupational Burnout: A Longitudinal MRI Study.

BACKGROUND: Studies on potential disruptions in rich club structure in nursing staff with occupational burnout are lacking. Moreover, existing studies on nurses with burnout are limited by their cross-sectional design. PURPOSE: To investigate rich club reorganization in nursing staff before and after the onset of burnout and the underlying impact of anatomical distance on such reconfiguration. STUDY TYPE: Prospective, longitudinal. POPULATION: Thirty-nine hospital nurses ( 23.67 ± 1.03 years old at baseline, 24.67 ± 1.03 years old at a follow-up within 1.5 years, 38 female). FIELD STRENGTH/SEQUENCE: Magnetization-prepared rapid gradient-echo and gradient-echo echo-planar imaging sequences at 3.0 T. ASSESSMENT: The Maslach Burnout Inventory and Symptom Check-List 90 testing were acquired at each MRI scan. Rich club structure was assessed at baseline and follow-up to determine whether longitudinal changes were related to burnout and to changes in connectivities with different anatomical distances (short-, mid-, and long range). STATISTICAL TESTS: Chi-square, paired-samples t, two-sample t, Mann-Whitney U tests, network-based statistic, Spearman correlation analysis, and partial least squares regression analysis. Significance level: Bonferroni-corrected P < 0.05 . RESULTS: In nurses who developed burnout: 1) Strengths of rich club, feeder, local, short-, mid-, and long-range connectivities were significantly decreased at follow-up compared with baseline. 2) At follow-up, strengths of above connectivities and that between A5m.R and dlPu.L were significantly correlated with emotional exhaustion (r ranges from -0.57 to -0.73) and anxiety scores (r = -0.56), respectively. 3) Longitudinal change (follow-up minus baseline) in connectivity strength between A5m.R and dlPu.L reflected change in emotional exhaustion score (r = 0.87). Longitudinal changes in strength of connectivities mainly involving parietal lobe were significantly decreased in nurses who developed burnout compared with those who did not. DATA CONCLUSION: In nurses after the onset of burnout, rich club reorganization corresponded to significant reductions in strength of connectivities with different anatomical distances. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

Alteration of White Matter Connectivity for MR-Guided Focused Ultrasound in the Treatment of Essential Tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear. PURPOSE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy. STUDY TYPE: Retrospective. SUBJECTS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison. FIELD STRENGTH/SEQUENCE: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence. ASSESSMENT: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05. RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement. DATA CONCLUSION: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 4.

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 vigilant maintenance and reorganization of rich-clubs in functional brain networks after total sleep deprivation.

BACKGROUND: Sleep deprivation strongly deteriorates the stability of vigilant maintenance. In previous neuroimaging studies of large-scale networks, neural variations in the resting state after sleep deprivation have been well documented, highlighting that large-scale networks implement efficient cognitive functions and attention regulation in a spatially hierarchical organization. However, alterations of neural networks during cognitive tasks have rarely been investigated. METHODS AND PURPOSES: The present study used a within-participant design of 35 healthy right-handed adults and used task-based functional magnetic resonance imaging to examine the neural mechanism of attentional decline after sleep deprivation from the perspective of rich-club architecture during a psychomotor vigilance task. RESULTS: We found that a significant decline in the hub disruption index was related to impaired vigilance due to sleep loss. The hierarchical rich-club architectures were reconstructed after sleep deprivation, especially in the default mode network and sensorimotor network. Notably, the relatively fast alert response compensation was correlated with the feeder organizational hierarchy that connects core (rich-club) and peripheral nodes. SIGNIFICANCES: Our findings provide novel insights into understanding the relationship of alterations in vigilance and the hierarchical architectures of the human brain after sleep deprivation, emphasizing the significance of optimal collaboration between different functional hierarchies for regular attention maintenance.

Altered structural connectome of children with auditory processing disorder: a diffusion MRI study.

Auditory processing disorder (APD) is a listening impairment that some school-aged children may experience despite having normal peripheral hearing. Recent resting-state functional magnetic resonance imaging (MRI) has revealed an alteration in regional functional brain topology in children with APD. However, little is known about the structural organization in APD. We used diffusion MRI data to investigate the structural connectome of 58 children from 8 to 14 years old diagnosed with APD (n = 29) and children without hearing complaints (healthy controls, HC; n = 29). We investigated the rich-club organization and structural connection differences between groups. The APD group showed similar rich-club organization and edge-wise connection compared with the HC group. However, at the regional level, we observed increased average path length (APL) and betweenness centrality in the right inferior parietal lobule and inferior precentral gyrus, respectively, in the APD group. Only HCs demonstrated a positive association between APL and the listening-in-spatialized-noise-sentences task in the left orbital gyrus. In line with previous findings, the current results provide evidence for altered structural networks at the regional level in the APD group, suggesting the involvement of multimodal deficits and a role for structure-function alteration in the listening difficulties of children with APD.

The relevance of rich club regions for functional outcome post-stroke is enhanced in women.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich-club) brain regions on functional outcome post-stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3-months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI-GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas-defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non-rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non-rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex-specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female-specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club-combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long-term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women.

Highly connected and highly variable: A Core brain network during resting state supports Propofol-induced unconsciousness.

Despite that leading theories of consciousness make diverging predictions for where and how neural activity gives rise to subjective experience, they all seem to partially agree that the neural correlates of consciousness (NCC) require globally integrated brain activity across a network of functionally specialized modules. However, it is not clear yet whether such functional configurations would be able to identify the NCC. We scanned resting-state fMRI data from 21 subjects during wakefulness, propofol-induced sedation, and anesthesia. Graph-theoretical analyses were conducted on awake fMRI data to search for the NCC candidates as brain regions that exhibit both high rich-clubness and high modular variability, which were found to locate in prefrontal and temporoparietal cortices. Another independent data set of 10 highly-sampled subjects was used to validate the NCC distribution at the individual level. Brain module-based dynamic analysis revealed two discrete reoccurring brain states, one of which was dominated by the NCC candidates (state 1), while the other state was predominately composed of primary sensory/motor regions (state 2). Moreover, state 1 appeared to be temporally more stable than state 2, suggesting that the identified NCC members could sustain conscious content as metastable network representations. Finally, we showed that the identified NCC was modulated in terms of functional connectedness and modular variability in response to the loss of consciousness induced by propofol anesthesia. This work offers a framework to search for neural correlates of consciousness by charting the brain network topology and provides new insights into understanding the roles of different regions in underpinning human consciousness.

Dynamic structure-function coupling across three major psychiatric disorders.

BACKGROUND: Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure-function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). METHODS: We quantified the dynamic structure-function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure-function coupling with the topological features of functional networks to examine how the structure-function relationship facilitates brain information communication over time. RESULTS: The dynamic structure-function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure-function coupling and the topological features of functional networks are altered in a manner indicative of state specificity. CONCLUSIONS: These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure-function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.

Trajectory of rich club properties in structural brain networks.

Many organizational principles of structural brain networks are established before birth and undergo considerable developmental changes afterwards. These include the topologically central hub regions and a densely connected rich club. While several studies have mapped developmental trajectories of brain connectivity and brain network organization across childhood and adolescence, comparatively little is known about subsequent development over the course of the lifespan. Here, we present a cross-sectional analysis of structural brain network development in N = 8066 participants aged 5-80 years. Across all brain regions, structural connectivity strength followed an "inverted-U"-shaped trajectory with vertex in the early 30s. Connectivity strength of hub regions showed a similar trajectory and the identity of hub regions remained stable across all age groups. While connectivity strength declined with advancing age, the organization of hub regions into a rich club did not only remain intact but became more pronounced, presumingly through a selected sparing of relevant connections from age-related connectivity loss. The stability of rich club organization in the face of overall age-related decline is consistent with a "first come, last served" model of neurodevelopment, where the first principles to develop are the last to decline with age. Rich club organization has been shown to be highly beneficial for communicability and higher cognition. A resilient rich club might thus be protective of a functional loss in late adulthood and represent a neural reserve to sustain cognitive functioning in the aging brain.

Abnormal white-matter rich-club organization in obsessive-compulsive disorder.

Rich-club organization is key to efficient global neuronal signaling and integration of information. Alterations interfere with higher-order cognitive processes, and are common to several psychiatric and neurological conditions. A few studies examining the structural connectome in obsessive-compulsive disorder (OCD) suggest lower efficiency of information transfer across the brain. However, it remains unclear whether this is due to alterations in rich-club organization. In the current study, the structural connectome of 28 unmedicated OCD patients, 8 of their unaffected siblings and 28 healthy controls was reconstructed by means of diffusion-weighted imaging and probabilistic tractography. Topological and weighted measures of rich-club organization and connectivity were computed, alongside global and nodal measures of network integration and segregation. The relationship between clinical scores and network properties was explored. Compared to healthy controls, OCD patients displayed significantly lower topological and weighted rich-club organization, allocating a smaller fraction of all connection weights to the rich-club core. Global clustering coefficient, local efficiency, and clustering of nonrich club nodes were significantly higher in OCD patients. Significant three-group differences emerged, with siblings displaying highest and lowest values in different measures. No significant correlation with any clinical score was found. Our results suggest weaker structural connectivity between rich-club nodes in OCD patients, possibly resulting in lower network integration in favor of higher network segregation. We highlight the need of looking at network-based alterations in brain organization and function when investigating the neurobiological basis of this disorder, and stimulate further research into potential familial protective factors against the development of OCD.

Aberrant dynamic structure-function relationship of rich-club organization in treatment-naïve newly diagnosed juvenile myoclonic epilepsy.

Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich-club organization-a core feature of the brain networks. Moreover, it is unclear how structure-function relationships dynamically change over time in JME. Here, we quantify the anatomical rich-club organization and dynamic structural and functional connectivity (SC-FC) coupling in 47 treatment-naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC-FC coupling were also calculated to examine the supporting of structure-function relationship to brain information transfer. The results showed that the anatomical rich-club organization was disrupted in the patient group, along with decreased connectivity strength among rich-club hub nodes. Furthermore, reduced SC-FC coupling in rich-club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor-cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC-FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC-FC coupling of rich-club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.

An Investigation into the Association Between Dopamine Receptor D1 Multilocus Genetic Variation, Multiparametric Magnetic Resonance Imaging, and Antidepressant Treatment.

BACKGROUND: Combining genetic variants with neuroimaging phenotypes may facilitate understanding of the biological mechanisms for the etiology and pharmacology of antidepressant treatment of major depressive disorder (MDD). PURPOSE: To explore the latent pathway of dopamine gene-hierarchical brain network-antidepressant treatment. STUDY TYPE: Retrospective. POPULATION: One hundred and sixty-eight MDD inpatients divided into responders (N = 98) or nonresponders (N = 70) based on the treatment outcome of antidepressant. FIELD STRENGTH/SEQUENCE: Diffusion tensors imaging and resting-state functional magnetic resonance imaging at 3.0T using echo-planar sequence. ASSESSMENT: Four genetic variations of the dopamine receptor D1 (DRD1) were genotyped. Strengths of rich-club, feeder, and local connections were calculated based on the rich-club organizations of structural and functional brain networks at baseline and following 4 weeks of selective serotonin reuptake inhibitor (SSRI) therapy. STATISTICAL TESTS: Logistic and linear regressions were used to analyze the impact of DRD1 multilocus genetic profile score on the treatment response of SSRI, and their associations with strengths of rich-club, feeder, and local connections. Mediation models were developed to explore the mediation role of rich-club organizations on the relationship between DRD1 and SSRI therapy response. A P value <0.05 was considered to be statistically significant. RESULTS: Multiple genetic variations of DRD1 were significantly related to the strengths of feeder connections both in structural and functional networks, and to the treatment response of SSRI. Furthermore, the strength of the structural feeder connection significantly modulated the effect of DRD1 variants on SSRI treatment outcome. DATA CONCLUSION: DRD1 displayed close connections both with SSRI treatment outcome and rich-club organizations of structural and functional data. Moreover, structural feeder connection played a mediating role in the relationship between DRD1 and antidepressant therapy. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 4.

Rich-Club Analysis of the Structural Brain Network in Cases with Cerebral Small Vessel Disease and Depression Symptoms.

BACKGROUND: Altered white matter brain networks have been extensively studied in cerebral small vessel disease (SVD). However, there exists currently a deficiency of comprehending the performance of changes within the structural networks of the brain in cases with cerebral SVD and depression symptoms. The main aim of the present research is to study the network topology behaviors and features of rich-club organization in SVD patients using graph theory and diffusion tensor imaging (DTI) to characterize changes in the microstructure of the brain. METHODS: DTI datasets were acquired from 26 SVD patients with symptoms of depression (SVD + D) and 26 SVD patients without symptoms of depression (SVD - D), and a series of neuropsychological assessments were completed. A structural network was created using a deterministic fiber tracking method. The analysis of rich-club was performed in company with analysis of the global network features of the network to characterize the topological properties of all subjects. RESULTS: DTI data were obtained from SVD patients who manifested symptoms of depression (SVD + D) and from control SVD patients (SVD - D). In comparison with SVD - D patients, SVD + D cases demonstrated a diminished coefficient of clustering along with lower global efficiencies and longer path length characteristics. Rich-club analysis showed SVD + D patients had decreased feeder connectivity and local connectivity strengths compared to SVD - D patients. Our data also showed that the feeder connections in the brain correlated significantly with the severity of depression in SVD + D patients. CONCLUSIONS: Our study revealed that SVD patients with depressive symptoms have disrupted white matter networks that characteristically have reduced network efficiency compared to the networks in other SVD patients. Disrupted information interactions among the regions of nonrich-club and rich-club in SVD cases are related to the severity of depression. Our data suggest that DTI may be utilized as an appropriate biomarker for the diagnosis of depression in comorbid SVD patients.

Whole-Brain Dynamics in Aging: Disruptions in Functional Connectivity and the Role of the Rich Club.

Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50-64 years versus older group (n = 310); age range, 65-91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

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.

Movements, embodiment and the emergence of decisions. Insights from insect navigation.

We readily infer that animals make decisions, but what this implies is usually not clearly defined. The notion of 'decision-making' ultimately stems from human introspection, and is thus loaded with anthropomorphic assumptions. Notably, the decision is made internally, is based on information, and precedes the goal directed behaviour. Also, making a decision implies that 'something' did it, thus hints at the presence of a cognitive mind, whose existence is independent of the decision itself. This view may convey some truth, but here I take the opposite stance. Using examples from research in insect navigation, this essay highlights how apparent decisions can emerge without a brain, how actions can precede information or how sophisticated goal directed behaviours can be implemented without neural decisions. This perspective requires us to shake off the idea that behaviour is a consequence of the brain; and embrace the concept that movements arise from - as much as participate in - distributed interactions between various computational centres - including the body - that reverberate in closed-loop with the environment. From this perspective we may start to picture how a cognitive mind can be the consequence, rather than the cause, of such neural and body movements.

Unifying the Notions of Modularity and Core-Periphery Structure in Functional Brain Networks during Youth.

At rest, human brain functional networks display striking modular architecture in which coherent clusters of brain regions are activated. The modular account of brain function is pervasive, reliable, and reproducible. Yet, a complementary perspective posits a core-periphery or rich-club account of brain function, where hubs are densely interconnected with one another, allowing for integrative processing. Unifying these two perspectives has remained difficult due to the fact that the methodological tools to identify modules are entirely distinct from the methodological tools to identify core-periphery structure. Here, we leverage a recently-developed model-based approach-the weighted stochastic block model-that simultaneously uncovers modular and core-periphery structure, and we apply it to functional magnetic resonance imaging data acquired at rest in 872 youth of the Philadelphia Neurodevelopmental Cohort. We demonstrate that functional brain networks display rich mesoscale organization beyond that sought by modularity maximization techniques. Moreover, we show that this mesoscale organization changes appreciably over the course of neurodevelopment, and that individual differences in this organization predict individual differences in cognition more accurately than module organization alone. Broadly, our study provides a unified assessment of modular and core-periphery structure in functional brain networks, offering novel insights into their development and implications for behavior.