Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Neural synchrony in cortical networks : history, concept and current status

Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies

Model-free reconstruction of neuronal network connectivity from calcium imaging signals

A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically unfeasible even in dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct approximations to network structural connectivities from network activity monitored through calcium fluorescence imaging. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time-series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the effective network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (e.g., bursting or non-bursting). We thus demonstrate how conditioning with respect to the global mean activity improves the performance of our method. [...] Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good reconstruction of the network clustering coefficient, allowing to discriminate between weakly or strongly clustered topologies, whereas on the other hand an approach based on cross-correlations would invariantly detect artificially high levels of clustering. Finally, we present the applicability of our method to real recordings of in vitro cortical cultures. We demonstrate that these networks are characterized by an elevated level of clustering compared to a random graph (although not extreme) and by a markedly non-local connectivity.Comment: 54 pages, 8 figures (+9 supplementary figures), 1 table; submitted for publicatio

Network perspectives on epilepsy using EEG/MEG source connectivity

The evolution of EEG/MEG source connectivity is both, a promising, and controversial advance in the characterization of epileptic brain activity. In this narrative review we elucidate the potential of this technology to provide an intuitive view of the epileptic network at its origin, the different brain regions involved in the epilepsy, without the limitation of electrodes at the scalp level. Several studies have confirmed the added value of using source connectivity to localize the seizure onset zone and irritative zone or to quantify the propagation of epileptic activity over time. It has been shown in pilot studies that source connectivity has the potential to obtain prognostic correlates, to assist in the diagnosis of the epilepsy type even in the absence of visually noticeable epileptic activity in the EEG/MEG, and to predict treatment outcome. Nevertheless, prospective validation studies in large and heterogeneous patient cohorts are still lacking and are needed to bring these techniques into clinical use. Moreover, the methodological approach is challenging, with several poorly examined parameters that most likely impact the resulting network patterns. These fundamental challenges affect all potential applications of EEG/MEG source connectivity analysis, be it in a resting, spiking, or ictal state, and also its application to cognitive activation of the eloquent area in presurgical evaluation. However, such method can allow unique insights into physiological and pathological brain functions and have great potential in (clinical) neuroscience

Stimulus and task-dependent gamma activity in monkey V1

The single unit doctrine proposes that each one of our percepts and sensations is represented by the activity of specialized high-level cells in the brain. A common criticism applied to this proposal is the one referred to as the "combinatorial problem". We are constantly confronted with unlimited combinations of elements and features, and yet we face no problem in recognizing patterns and objects present in visual scenes. Are there enough neurons in the brain to singly code for each one of our percepts? Or is it the case that perceptions are represented by the distributed activity of different neuronal ensembles? We lack a general theory capable of explaining how distributed information can be efficiently integrated into single percepts. The working hypothesis here is that distributed neuronal ensembles signal relations present in the stimulus by selectively synchronizing their spiking responses. Synchronization is generally associated with oscillatory activity in the brain. Gamma oscillations in particular have been linked to various integrative processes in the visual system. Studies in anesthetized animals have shown a conspicuous increase in power for the gamma frequency band (30 to 60 Hz) in response to visual stimuli. Recently, these observations have been extended to behavioral studies which addressed the role of gamma activity in cognitive processes demanding selective attention. The initial motivation for carrying out this work was to test if the binding-by-synchronization (BBS) hypothesis serves as a neuronal mechanism for perceptual grouping in the visual system. To this aim we used single and superimposed grating stimuli. Superimposed gratings (plaids) are bi-stable stimuli capable of eliciting different percepts depending on their physical characteristics. In this way, plaids can be perceived either as a single moving surface (pattern plaids), or as two segregated surfaces drifting in different directions (component plaids). While testing the BBS hypothesis, we performed various experiments which addressed the role of both stimulus and cortical architecture on the properties of gamma oscillations in the primary visual cortex (V1) of monkeys. Additionally, we investigated whether gamma activity could also be modulated by allocating attention in time. Finally, we report on gamma-phase shifts in area V1, and how they depend on the level of neuronal activation. ...Einleitung: Die visuelle Hirnforschung hat eine große Informationsmenge über die analytischen Fähigkeiten des Nervensystems zusammengetragen. Die Einführung von Einzelzellableitungen ermöglichte eine detaillierte Beschreibung der Eigenschaften rezeptiver Felder im Sehsystem. Konzentrische rezeptive Felder in der Netzhaut antworten optimal auf einen Luminanzkontrast in ihren On- und Off-Regionen. Antworteigenschaften entwickeln sich schrittweise entlang der Sehbahn, indem zunehmend komplexere Eigenschaften des visuellen Reizes extrahiert werden. Die Pionierarbeiten von David Hubel und Torsten Wiesel beschrieben zunächst Orientierung- und Richtungsselektivität von Neuronen in frühen visuellen Kortexarealen. Später fand man Einzelzellen im medialen Temporallappen, die auf komplexe Objekte wie Hände und Gesichter antworten. Die Hirnforschung ist daher lange davon ausgegangen, dass die Repräsentation komplexer Objekte eine natürliche Entfaltung von Konvergenz entlang der Sehbahn darstellt. Zellen, welche auf elementare Merkmale des Stimulus antworteten, bildeten so durch ihr Muster anatomischer Verbindungen schrittweise die spezialisierten Neurone in höheren visuellen Arealen. Diese Sichtweise zeigt allerdings Limitationen auf. Eine beständige Kritik, die an der "Einzelzelldoktrin" geübt wird, ist das sogenannte kombinatorische Problem. Obwohl wir ständig mit einer unbegrenzten Fülle an Kombinationen verschiedener Elemente und Merkmale konfrontiert sind, laufen wir selten Gefahr, Muster und Objekte in einer visuellen Szene nicht zu erkennen. Ist es überhaupt möglich, dass jedes unserer möglichen Perzepte durch die Antwort eines einzelnen hoch spezialisierten Neurons im Hirn kodiert wird? Falls nicht, welcher Mechanismus könnte einen relationalen Code darstellen, der es ermöglicht, die Aktivität verschiedener neuronaler Ensembles zu integrieren? Die Anforderungen an einen solchen Mechanismus treten besonders hervor, wenn man sich die verteilte Struktur der visuellen Verarbeitung verdeutlicht. Die Merkmalsextraktion entlang der Sehbahn führt unvermeidbar zu einer räumlich verstreuten Repräsentation eines visuellen Reizes. Zusätzlich kommen parallele Bahnen neuronaler Verarbeitung im Hirn häufig vor. Es fehlt eine universale Theorie darüber, wie die verteilte Information effizient in eine einzige Wahrnehmung integriert wird. Die Arbeitshypothese hier lautet, dass das Hirn die Zeitdomäne benutzt, um visuelle Informationen zu integrieren und zu verarbeiten. Konkret würden neuronale Ensemble die aus dem Stimulus hervorgehenden Beziehungen durch eine selektive Synchronisation ihrer Aktionspotenziale signalisieren. Synchronisation ist normalerweise mit oszillatorischer Hirnaktivität assoziiert. Besonders die Oszillationen im Gamma Frequenzband sind mit verschiedensten integrativen Prozessen im Sehsystem in Verbindung gebracht worden. Arbeiten an anästhesierten Tieren haben einen auffälligen Anstieg von Energie im Gamma Frequenzband (30-60 Hz) unter visueller Stimulation gezeigt. Kürzlich sind diese Beobachtungen auf Verhaltensstudien ausgeweitet worden, welche die Rolle von Gamma Aktivität bei der für kognitive Prozesse erforderlichen gerichteten Aufmerksamkeit untersuchen. Die ursprüngliche Motivation dieser Arbeit war es, die von Wolf Singer und Mitarbeitern formulierte "binding-bysynchronization (BBS)" Hypothese zu testen. Dies wurde durch die Ableitung neuronaler Antworten in V1 bei Darbietung eines Paars übereinander gelegter Balkengitter ("Plaid" Stimulus) angegangen. Physikalische Manipulationen der Luminanz in Unterregionen des Plaid-Stimulus können die Wahrnehmung zugunsten der Bewegung der Einzelkomponenten (zwei Objekte, die sich übereinander schieben) oder der Bewegung des Gesamtmusters (ein einziges sich in eine gemeinsame Richtung bewegendes Objekt) beeinflussen. Die gleichzeitige Ableitung von zwei Neuronen, die jeweils nur selektiv auf eines der beiden Balkengitter antworteten, ermöglichte es uns, zwei Vorhersagen der BBS Hypothese zu testen. Falls beide V1 Neurone auf dasselbe Balkengitter antworteten, sollten sie ihre Aktivität unabhängig davon, ob das Plaid in Einzelkomponenten oder als Gesamtmuster wahrgenommen würde, synchronisieren. Der Grund dafür wäre, dass beide Neurone auf dasselbe Objekt reagierten. Im zweiten Fall antworten beide Ableitstellen auf jeweils eine der beiden Balkengitterkomponenten. Hier sagt die BBS Hypothese voraus, dass beide ihre Aktivität nur bei Gesamtmusterbewegung synchronisieren würden, da sie nur in dieser Bedingung auf dasselbe Objekt antworten würden. ..

From locomotion to dance and back : exploring rhythmic sensorimotor synchronization

Le rythme est un aspect important du mouvement et de la perception de l’environnement. Lorsque l’on danse, la pulsation musicale induit une activité neurale oscillatoire qui permet au système nerveux d’anticiper les évènements musicaux à venir. Le système moteur peut alors s’y synchroniser. Cette thèse développe de nouvelles techniques d’investigation des rythmes neuraux non strictement périodiques, tels que ceux qui régulent le tempo naturellement variable de la marche ou la perception rythmes musicaux. Elle étudie des réponses neurales reflétant la discordance entre ce que le système nerveux anticipe et ce qu’il perçoit, et qui sont nécessaire pour adapter la synchronisation de mouvements à un environnement variable. Elle montre aussi comment l’activité neurale évoquée par un rythme musical complexe est renforcée par les mouvements qui y sont synchronisés. Enfin, elle s’intéresse à ces rythmes neuraux chez des patients ayant des troubles de la marche ou de la conscience.Rhythms are central in human behaviours spanning from locomotion to music performance. In dance, self-sustaining and dynamically adapting neural oscillations entrain to the regular auditory inputs that is the musical beat. This entrainment leads to anticipation of forthcoming sensory events, which in turn allows synchronization of movements to the perceived environment. This dissertation develops novel technical approaches to investigate neural rhythms that are not strictly periodic, such as naturally tempo-varying locomotion movements and rhythms of music. It studies neural responses reflecting the discordance between what the nervous system anticipates and the actual timing of events, and that are critical for synchronizing movements to a changing environment. It also shows how the neural activity elicited by a musical rhythm is shaped by how we move. Finally, it investigates such neural rhythms in patient with gait or consciousness disorders

Propagation of beta/gamma rhythms in the cortico-basal ganglia circuits of the Parkinsonian rat

Much of the motor impairment associated with Parkinson’s disease is thought to arise from pathological activity in the networks formed by the basal ganglia (BG) and motor cortex. To evaluate several hypotheses proposed to explain the emergence of pathological oscillations in Parkinsonism, we investigated changes to the directed connectivity in BG networks following dopamine depletion. We recorded local field potentials (LFPs) in the cortex and basal ganglia of rats rendered Parkinsonian by injection of 6-hydroxydopamine (6-OHDA) and in dopamine-intact controls. We performed systematic analyses of the networks using a novel tool for estimation of directed interactions (Non-Parametric Directionality, NPD). Additionally, we used a ‘conditioned’ version of the NPD analysis which reveals the dependence of the correlation between two signals upon a third reference signal. We find evidence of the dopamine dependency of both low beta (14-20 Hz) and high beta/low gamma (20-40 Hz) directed interactions within the network. Notably, 6-OHDA lesions were associated with enhancement of the cortical “hyper-direct” connection to the subthalamic nucleus (STN) and its feedback to the cortex and striatum. We find that pathological beta synchronization resulting from 6-OHDA lesioning is widely distributed across the network and cannot be located to any individual structure. Further, we provide evidence that high beta/gamma oscillations propagate through the striatum in a pathway that is independent of STN. Rhythms at high beta/gamma show susceptibility to conditioning that indicates a hierarchical organization when compared to low beta. These results further inform our understanding of the substrates for pathological rhythms in salient brain networks in Parkinsonism