Suchergebnisse

Does the human brain have a central connective core, and, if so, how costly is it?Noninvasive imaging data allow the construction of network maps of the human brain, recording its structural and functional connectivity. A number of studies have reported on various characteristic network attributes, such as a tendency toward local clustering, high global efficiency, the prevalence of specific network motifs, and a pronounced community structure with several anatomically and functionally defined modules and interconnecting hub regions (Bullmore & Sporns, 2009; van den Heuvel & Hulshoff Pol, 2010; Sporns, 2011). Hubs are of particular interest in studies of the brain since they may play crucial roles in integrative processes and global brain communication, thought to be essential for many aspects of higher brain function. Indeed, hubs have been shown to correspond to brain regions that exhibit complex physiological responses and maintain widespread and diverse connection profiles with other parts of the brain. We asked if, in addition to being highly connected, brain hubs would also exhibit a strong tendency to be mutually interconnected, forming what has been called a "rich club" (Colizza et al., 2006). Rich club organization is present in a network if sets of high-degree nodes exhibit denser mutual connections than predicted on the basis of the degree sequence alone. We investigated rich club organization in the human brain in datasets that recorded weighted projections among different anatomical regions of the cerebral cortex, recorded from several cohorts of healthy human volunteers (van den Heuvel & Sporns, 2011; van den Heuvel et al., 2012).

Brain function relies on the flexible integration of a diverse set of segregated cortical/nmodules, with the structural connectivity of the brain being a fundamentally important factor/nin shaping the brain"s functional dynamics. Following up on macroscopic studies showing the/nexistence of centrally connected nodes in the mammalian brain, combined with the notion that/nthese putative brain hubs may form a dense interconnected "rich club" collective, we/nhypothesized that brain connectivity might involve a rich club type of architecture to promote/na repertoire of different and flexibly accessible brain functions. With the rich club suggested/nto play an important role in global brain communication, examining the effects of a rich club/norganization on the functional repertoire of physical systems in general, and the brain in/nparticular, is of keen interest. Here we elucidate these effects using a spin glass model of/nneural networks for simulating stable configurations of cortical activity. Using simulations,/nwe show that the presence of a rich club increases the set of attractors and hence the diversity/nof the functional repertoire over and above the effects produced by scale free type topology/nalone. Within the networks" overall functional repertoire rich nodes are shown to be important/nfor enabling a high level of dynamic integrations of low-degree nodes to form functional/nnetworks. This suggests that the rich club serves as an important backbone for numerous co-/nactivation patterns among peripheral nodes of the network. In addition, applying the spin/nglass model to empirical anatomical data of the human brain, we show that the positive effects/non the functional repertoire attributed to the rich club phenomenon can be observed for the/nbrain as well. We conclude that a rich club organization in network architectures may be/ncrucial for the facilitation and integration of a diverse number of segregated functions. ; Authors MS and RG were supported by the European Research Council under the European Union's Seventh Framework Programme (ERC-2010-AdG, ERC grant agreement no. 269853). Author GD was supported by the ERC Advanced Grant: DYSTRUCTURE (n. 295129), by the Spanish Research ProjectSAF2010-16085 and by European Community's Seventh Framework Programme under the project "BrainScales" (project number 269921). Author MPvdH was supported by a VENI grant of The Netherlands Organization for Scientific Research (NWO) (451-12-001) and by a Fellowship of the Brain Center Rudolf Magnus.

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. ; This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 753896 (MS). This study was in part supported by the NIH-NINDS K23NS064052, R01NS082285, and R01NS086905 (NR); American Heart Association/Bugher Foundation Centers for Stroke Prevention Research and ...

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. ; A.E. was supported by the Catalan project Imagenoma de L'Envelliment (Aging Imageomics Study). G.D. was supported by the Spanish Ministry of Economy and Competitiveness, Spain (grant agreement number PSI2016- 75688-P, MINECO/AEI/FEDER-EU); European Union's Horizon 2020 FET Flagship Human Brain Project (grant agreement number 785907, HBP SGA2); the Catalan Research Support, Spain (grant agreement number 2017 SGR 1545) and La Marató TV3 2017 (grant agreement 201725.33).

Cognition is hypothesized to require the globally coordinated, functionally relevant integration of otherwise segregated information processing carried out by specialized brain regions. Studies of the macroscopic connectome as well as recent neuroimaging and neuromodeling research have suggested a densely connected collective of cortical hubs, termed the rich club, to provide a central workspace for such integration. In order for rich club regions to fulfill this role they must dispose of a dynamic mechanism by which they can actively shape networks of brain regions whose information processing needs to be integrated. A potential candidate for such a mechanism comes in the form of oscillations which might be employed to establish communication channels among relevant brain regions. We explore this possibility using an integrative approach combining whole-brain computational modeling with neuroimaging, wherein we investigate the local dynamics model brain regions need to exhibit in order to fit (dynamic) network behavior empirically observed for resting as well as a range of task states. We find that rich club regions largely exhibit oscillations during task performance but not during rest. Furthermore, oscillations exhibited by rich club regions can harmonize a set of asynchronous brain regions thus supporting functional coupling among them. These findings are in line with the hypothesis that the rich club can actively shape integration using oscillations. ; Authors MS and RG were supported by the European Research Council under the European Union's Seventh Framework Programme (ERC-2010-AdG, ERC grant agreement no. 269853). Author GD was supported by the ERC Advanced Grant: DYSTRUCTURE (no. 295129), by the Spanish Research ProjectSAF2010-16085 and by European Community's Seventh Framework Programme under the project "BrainScales" (project number 269921). Author MPvdH was supported by a VENI grant of The Netherlands Organization for Scientific Research (NWO) (451-12-001) and by a Fellowship of the Brain Center Rudolf Magnus.

The large-scale structural ingredients of the brain and neural connectomes have been identified in recent years. These are, similar to the features found in many other real networks: the arrangement of brain regions into modules and the presence of highly connected regions (hubs) forming rich-clubs. Here, we examine how modules and hubs shape the collective dynamics on networks and we find that both ingredients lead to the emergence of complex dynamics. Comparing the connectomes of C. elegans, cats, macaques and humans to surrogate networks in which either modules or hubs are destroyed, we find that functional complexity always decreases in the perturbed networks. A comparison between simulated and empirically obtained resting-state functional connectivity indicates that the human brain, at rest, lies in a dynamical state that reflects the largest complexity its anatomical connectome can host. Last, we generalise the topology of neural connectomes into a new hierarchical network model that successfully combines modular organisation with rich-club forming hubs. This is achieved by centralising the cross-modular connections through a preferential attachment rule. Our network model hosts more complex dynamics than other hierarchical models widely used as benchmarks. ; This work has been supported by (G.Z.L.) the European Union Seventh Framework Programme FP7/2007–2013 under grant agreement number PIEF-GA-2012-331800, the German Federal Ministry of Education and Research (Bernstein Center II, grant no. 01GQ1001A), and the European Union's Horizon 2020 research and innovation programme under grant agreement No. 720270 (HBP SGA1). Y.C. and C.S.Z. were supported by the Hong Kong Baptist University (HKBU) Strategic Development Fund, the Hong Kong Research Grant Council (GRF12302914), HKBU FRG2/14-15/025 and the National Natural Science Foundation of China (No. 11275027). G.D. is supported by the European Research Council Advanced Grant: DYSTRUCTURE (295129) and by the Spanish Research Project PSI2013-42091-P; and M.L.K. by the European Research Council Consolidator Grant: CAREGIVING (615539).

Zusammenfassung
Die jüngsten Erweiterungen der EU auf mittlerweile 27 Mitgliedsstaaten haben den europäischen Integrationsprozeß in ein neues Stadium geführt. Zielsetzungen und institutionelle Vorgaben, die für die ursprüngliche Gemeinschaft von sechs eng benachbarten und ähnlich entwickelten Volkswirtschaften vorgesehen waren, verlieren teilweise in einer Gemeinschaft von 27 und mehr, zunehmend heterogenen Mitgliedsländern an Relevanz. Es wird immer schwieriger, gemeinsame Entscheidungen zu treffen, wodurch dem Prozeß einer weiteren Vertiefung der Integration Grenzen gesetzt werden. Die Europäische Union hat auf diese Entwicklungen mit der Einführung des Instruments der sog. "Verstärkten Zusammenarbeit" einer Untergruppe der gesamten Gemeinschaft reagiert. Diese Option ermöglicht Integrationsfortschritte, auch wenn sich noch nicht alle Mitgliedsländer daran beteiligen wollen. In Verbindung mit dem im Verfassungsentwurf vorgesehenen Sezessionsrecht kann gezeigt werden, daß "Clubs im Club" mit flexibler Eintritts- und Austrittsmöglichkeit den Zielkonflikt zwischen Vertiefung und Erweiterung der EU verringern und zugleich Elemente des Systemwettbewerbs im Integrationsprozeß verankern können.