Relationship of topology, multiscale phase synchronization, and state transitions in human brain networks

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram(EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are ��progressive and earlier�� or ��abrupt but delayed�� account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations. ? 2017 Kim, Kim, Mashour and Lee.115sciescopu

First-order synchronization transition in a large population of strongly coupled relaxation oscillators.

Onset and loss of synchronization in coupled oscillators are of fundamental importance in understanding emergent behavior in natural and man-made systems, which range from neural networks to power grids. We report on experiments with hundreds of strongly coupled photochemical relaxation oscillators that exhibit a discontinuous synchronization transition with hysteresis, as opposed to the paradigmatic continuous transition expected from the widely used weak coupling theory. The resulting first-order transition is robust with respect to changes in network connectivity and natural frequency distribution. This allows us to identify the relaxation character of the oscillators as the essential parameter that determines the nature of the synchronization transition. We further support this hypothesis by revealing the mechanism of the transition, which cannot be accounted for by standard phase reduction techniques

Coherence of Visual-Evoked Gamma Oscillations Is Disrupted by Propofol but Preserved Under Equipotent Doses of Isoflurane

Previous research demonstrates that the underlying state of the brain influences how sensory stimuli are processed. Canonically, the state of the brain has been defined by quantifying the spectral characteristics of spontaneous fluctuations in local field potentials (LFP). Here, we utilized isoflurane and propofol anesthesia to parametrically alter the spectral state of the murine brain. With either drug, we produce slow wave activity, with low anesthetic doses, or burst suppression, with higher doses. We find that while spontaneous LFP oscillations were similar, the average visual-evoked potential (VEP) was always smaller in amplitude and shorter in duration under propofol than under comparable doses of isoflurane. This diminished average VEP results from increased trial-to-trial variability in VEPs under propofol. One feature of single trial VEPs that was consistent in all animals was visual-evoked gamma band oscillation (20–60 Hz). This gamma band oscillation was coherent between trials in the early phase (<250 ms) of the visual evoked potential under isoflurane. Inter trial phase coherence (ITPC) of gamma oscillations was dramatically attenuated in the same propofol anesthetized mice despite similar spontaneous oscillations in the LFP. This suggests that while both anesthetics lead to loss of consciousness (LOC), elicit slow oscillations and burst suppression, only the isoflurane permits phase resetting of gamma oscillations by visual stimuli. These results demonstrate that accurate characterization of a brain state must include both spontaneous as well as stimulus-induced perturbations of brain activity

Sincronização induzida por forças externas em redes modulares

Orientador: Marcus Aloizio Martinez de AguiarTese (doutorado) - Universidade Estadual de Campinas, Instituto de Física Gleb WataghinResumo: Neste trabalho estudamos a sincronização de osciladores de Kuramoto sujeitos a forças externas em redes modulares complexas. A motivação está na dinâmica neuronal que ocorre durante o processamento de informação no córtex cerebral que parece estar relacionada ao disparo síncrono de grupos de neurônios. A organização dos neurônios é modular, com agrupamentos associados a diferentes funções e estruturas cerebrais, e precisa responder constantemente a estímulos externos. Anormalidades no processo de sincronização, como a ativação de múltiplos módulos têm sido associadas à doenças como epilepsia e Alzheimer. Nesse contexto, estudamos o comportamento de osciladores de Kuramoto forçados, onde apenas uma fração deles é submetida a uma força externa periódica. Quando todos os osciladores recebem o estímulo externo o sistema sempre sincroniza com a força externa se a sua intensidade for suficientemente grande. Mostramos que as condições para a sincronização global dependem da fração de nós forçada e da topologia da rede e das intensidades do acoplamento interno e da força externa. Desenvolvemos cálculos numéricos e analíticos para a força crítica que leva a rede à sincronização global em função da fração de osciladores forçados. Como uma aplicação estudamos a resposta da rede de junções elétricas do \textit{C. elegans} ao estímulo externo usando o modelo de Kuramoto parcialmente forçado, aplicando a força a grupos específicos de neurônios. Os estímulos foram aplicados a três módulos topológicos, dois gânglios, especificados por sua localização anatômica, e aos grupos funcionais compostos por todos os neurônios sensoriais e motores. Encontramos que os módulos topológicos não contêm grupos puramente anatômicos ou classes funcionais e que estimular diferentes classes neuronais leva a respostas muito diferentes, medidas em termos de sincronização e correlações de velocidade de fase. Em todos os casos a estrutura modular impede a sincronização global, protegendo o sistema de falhas. As respostas aos estímulos aplicados aos módulos topológicos e funcionais mostram padrões pronunciados de correlação ou anti-correlação com outros módulos que não foram observados quando o estímulo foi aplicado a um gânglio com neurônios funcionais mistos. Todos os códigos e dados utilizados nesta tese estão disponível em [1]Abstract: In this work we study the synchronization of Kuramoto oscillators driven by external forces in complex modular networks. The motivation is the neuronal dynamics that takes place during information processing in the neural cortex, which seems to be related to the synchronous firing of groups of neurons. The neuron organization is modular, with clusters associated to different functions and brain structures, and need to constantly respond to external stimuli. Abnormalities in the process of synchronization, such as the activation of multiple modules, have been associated with epilepsy and Alzheimer's disease. In this context, we study the behavior of forced Kuramoto oscillators where only a fraction of them is subjected to a periodic external force. When all oscillators receive the external drive the system always synchronize with the periodic force if its intensity is sufficiently large. We show that the conditions for global synchronization depend on the fraction of nodes being forced and on network topology, strength of internal couplings and intensity of external forcing. We develop numerical and analytical calculations for the critical force for global synchronization as a function of the fraction of forced oscillators. As an application we study the response of the electric junction \textit{C. elegans} network to external stimuli using the partially forced Kuramoto model and applying the force to specific groups of neurons. Stimuli were applied to three topological modules, two ganglia, specified by their anatomical localization, and to the functional groups composed of all sensory and motoneurons. We found that topological modules do not contain purely anamotical groups or functional classes, and that stimulating different classes of neurons lead to very different responses, measured in terms of synchronization and phase velocity correlations. In all cases the modular structure hindered full synchronization, protecting the system from seizures. The responses to stimuli applied to topological and functional modules showed pronounced patterns of correlation or anti-correlation with other modules that were not observed when the stimulus was applied to a ganglion with mixed functional neurons. All codes and data used in this thesis are available in [1]DoutoradoFísicaDoutora em Ciências141021/2017-9CNP

Anesthetic-induced unresponsiveness: Electroencephalographic correlates and subjective experiences

Anesthetic drugs can induce reversible alterations in responsiveness, connectedness and consciousness. The measures based on electroencephalogram (EEG) have marked potential for monitoring the anesthetized state because of their relatively easy use in the operating room. In this study, 79 healthy young men participated in an awake experiment, and 47 participants continued to an anesthesia experiment where they received either dexmedetomidine or propofol as target-controlled infusion with stepwise increments until the loss of responsiveness. The participants were roused during the constant drug infusion and interviewed. The drug dose was increased to 1.5-fold to achieve a deeper unresponsive state. After regaining responsiveness, the participants were interviewed. EEG was measured throughout the experiment and the N400 event-related potential component and functional and directed connectivity were studied. Prefrontal-frontal connectivity in the alpha frequency band discriminated the states that differed with respect to responsiveness or drug concentration. The net direction of connectivity was frontal-to-prefrontal during unresponsiveness and reversed back to prefrontal-to-frontal upon return of responsiveness. The understanding of the meaning of spoken language, as measured with the N400 effect, was lost along with responsiveness but, in the dexmedetomidine group, the N400 component was preserved suggesting partial preservation of the processing of words during anesthetic-induced unresponsiveness. However, the N400 effect could not be detected in all the awake participants and the choice of analysis method had marked impact on its detection rate at the individual-level. Subjective experiences were common during unresponsiveness induced by dexmedetomidine and propofol but the experiences most often suggested disconnectedness from the environment. In conclusion, the doses of dexmedetomidine or propofol minimally sufficient to induce unresponsiveness do not render the participants unconscious and dexmedetomidine does not completely abolish the processing of semantic stimuli. The local anterior EEG connectivity in the alpha frequency band may have potential in monitoring the depth of dexmedetomidine- and propofol-induced anesthesia.Anesteettien aiheuttama vastauskyvyttömyys: aivosähkökäyräpohjaiset korrelaatit ja subjektiiviset kokemukset Anestesialääkkeillä voidaan saada aikaan palautuvia muutoksia vastauskykyisyydessä, kytkeytyneisyydessä ja tajunnassa. Aivosähkökäyrään (EEG) pohjautuvat menetelmät tarjoavat lupaavia mahdollisuuksia mitata anestesian vaikutusta aivoissa, sillä niitä on suhteellisen helppo käyttää leikkaussalissa. Tässä tutkimuksessa 79 tervettä nuorta miestä osallistui valvekokeeseen ja 47 heistä jatkoi anestesiakokeeseen. Anestesiakokeessa koehenkilöille annettiin joko deksmedetomidiinia tai propofolia tavoiteohjattuna infuusiona nousevia annosportaita käyttäen, kunnes he menettivät vastauskykynsä. Koehenkilöt herätettiin tasaisen lääkeinfuusion aikana ja haastateltiin. Koko kokeen ajan mitattiin EEG:tä, josta tutkittiin N400-herätevastetta sekä toiminnallista ja suunnattua konnektiivisuutta. Prefrontaali-frontaalivälillä mitattu konnektiivisuus alfa-taajuuskaistassa erotteli toisistaan tilat, jotka erosivat vastauskykyisyyden tai lääkepitoisuuden suhteen. Konnektiivisuuden vallitseva suunta oli frontaalialueilta prefrontaalialueille vastauskyvyttömyyden aikana, mutta se kääntyi takaisin prefrontaalisesta frontaaliseen kulkevaksi koehenkilöiden vastauskyvyn palatessa. N400-efektillä mitattu puhutun kielen ymmärtäminen katosi vastauskyvyn menettämisen myötä. Deksmedetomidiiniryhmässä N400-komponentti säilyi, mikä viittaa siihen, että anesteettien aiheuttaman vastauskyvyttömyyden aikana sanojen prosessointi voi säilyä osittain. Yksilötasolla N400-efektiä ei kuitenkaan havaittu edes kaikilla hereillä olevilla henkilöillä, ja analyysimenetelmän valinnalla oli suuri vaikutus herätevasteen havaitsemiseen. Subjektiiviset kokemukset olivat yleisiä deksmedetomidiinin ja propofolin aiheuttaman vastauskyvyttömyyden aikana, mutta kokemukset olivat usein ympäristöstä irtikytkeytyneitä. Yhteenvetona voidaan todeta, että deksmedetomidiini- ja propofoliannokset, jotka juuri ja juuri riittävät aikaansaamaan vastauskyvyttömyyden, eivät aiheuta tajuttomuutta. Deksmedetomidiini ei myöskään täysin estä merkityssisällöllisten ärsykkeiden käsittelyä. Frontaalialueen sisällä EEG:llä mitattu konnektiivisuus alfataajuuskaistassa saattaa olla tulevaisuudessa hyödyllinen menetelmä deksmedetomidiini- ja propofolianestesian syvyyden mittaamiseksi

Self-organized explosive synchronization in complex networks: Emergence of synchronization bombs

We introduce the concept of synchronization bombs as large networks of coupled heterogeneous oscillators that operate in a bistable regime and abruptly transit from incoherence to phase-locking (or vice-versa) by adding (or removing) one or a few links. Here we build a self-organized and stochastic version of these bombs, by optimizing global synchrony with decentralized information in a competitive link-percolation process driven by a local rule. We find explosive fingerprints on the emerging network structure, including frequency-degree correlations, disassortative patterns and a delayed percolation threshold. We show that these bomb-like transitions can be designed both in systems of Kuramoto -- periodic -- and R\"ossler -- chaotic -- oscillators and in a model of cardiac pacemaker cells. We analytically characterize the transitions in the Kuramoto case by combining a precise collective coordinates approach and the Ott-Antonsen ansatz. Furthermore, we study the robustness of the phenomena under changes in the main parameters and the unexpected effect of optimal noise in our model. Our results propose a minimal self-organized mechanism of network growth to understand and control explosive synchronization in adaptive biological systems like the brain and engineered ones like power-grids or electronic circuits. From a theoretical standpoint, the emergence of synchronization explosions and bistability induced by localized structural perturbations -- without any fine-tuning of global parameters -- joins explosive synchronization and percolation under the same mechanistic framework.Comment: 17 pages, 9 figure