Zero-lag long-range synchronization of Hodgkin-Huxley neurons is enhanced by dynamical relaying : poster presentation

Background The synchrony hypothesis postulates that precise temporal synchronization of different pools of neurons conveys information that is not contained in their firing rates. The synchrony hypothesis had been supported by experimental findings demonstrating that millisecond precise synchrony of neuronal oscillations across well separated brain regions plays an essential role in visual perception and other higher cognitive tasks [1]. Albeit, more evidence is being accumulated in favour of its role as a binding mechanism of distributed neural responses, the physical and anatomical substrate for such a dynamic and precise synchrony, especially zero-lag even in the presence of non-negligible delays, remains unclear. Here we propose a simple network motif that naturally accounts for zero-lag synchronization for a wide range of temporal delays [3]. We demonstrate that zero-lag synchronization between two distant neurons or neural populations can be achieved by relaying the dynamics via a third mediating single neuron or population. Methods We simulated the dynamics of two Hodgkin-Huxley neurons that interact with each other via an intermediate third neuron. The synaptic coupling was mediated through alpha-functions. Individual temporal delays of the arrival of pre-synaptic potentials were modelled by a gamma distribution. The strength of the synchronization and the phase-difference between each individual pairs were derived by cross-correlation of the membrane potentials. Results In the regular spiking regime the two outer neurons consistently synchronize with zero phase lag irrespective of the initial conditions. This robust zero-lag synchronization naturally arises as a consequence of the relay and redistribution of the dynamics performed by the central neuron. This result is independent on whether the coupling is excitatory or inhibitory and can be maintained for arbitrarily long time delays (see Fig. 1). Conclusion We have presented a simple and extremely robust network motif able to account for the isochronous synchronization of distant neural elements in a natural way. As opposed to other possible mechanisms of neural synchronization, neither inhibitory coupling, gap junctions nor precise tuning of morphological parameters are required to obtain zero-lag synchronized neuronal oscillation

Mechanisms of Zero-Lag Synchronization in Cortical Motifs

Zero-lag synchronization between distant cortical areas has been observed in a diversity of experimental data sets and between many different regions of the brain. Several computational mechanisms have been proposed to account for such isochronous synchronization in the presence of long conduction delays: Of these, the phenomenon of "dynamical relaying" - a mechanism that relies on a specific network motif - has proven to be the most robust with respect to parameter mismatch and system noise. Surprisingly, despite a contrary belief in the community, the common driving motif is an unreliable means of establishing zero-lag synchrony. Although dynamical relaying has been validated in empirical and computational studies, the deeper dynamical mechanisms and comparison to dynamics on other motifs is lacking. By systematically comparing synchronization on a variety of small motifs, we establish that the presence of a single reciprocally connected pair - a "resonance pair" - plays a crucial role in disambiguating those motifs that foster zero-lag synchrony in the presence of conduction delays (such as dynamical relaying) from those that do not (such as the common driving triad). Remarkably, minor structural changes to the common driving motif that incorporate a reciprocal pair recover robust zero-lag synchrony. The findings are observed in computational models of spiking neurons, populations of spiking neurons and neural mass models, and arise whether the oscillatory systems are periodic, chaotic, noise-free or driven by stochastic inputs. The influence of the resonance pair is also robust to parameter mismatch and asymmetrical time delays amongst the elements of the motif. We call this manner of facilitating zero-lag synchrony resonance-induced synchronization, outline the conditions for its occurrence, and propose that it may be a general mechanism to promote zero-lag synchrony in the brain.Comment: 41 pages, 12 figures, and 11 supplementary figure

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

Enhancing Synchrony in Chaotic Oscillators by Dynamic Relaying

In a chain of mutually coupled oscillators, the coupling threshold for synchronization between the outermost identical oscillators decreases when a type of impurity (in terms of parameter mismatch) is introduced in the inner oscillator(s). The outer oscillators interact indirectly via dynamic relaying, mediated by the inner oscillator(s). We confirm this enhancing of critical coupling in the chaotic regimes of R\"ossler system in absence of coupling delay and in Mackey-Glass system with delay coupling. The enhancing effect is experimentally verified in electronic circuit of R\"ossler oscillators.Comment: 4 pages, 9 figure

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. ..

Investigating the role of fast-spiking interneurons in neocortical dynamics

PhD ThesisFast-spiking interneurons are the largest interneuronal population in neocortex. It is well documented that this population is crucial in many functions of the neocortex by subserving all aspects of neural computation, like gain control, and by enabling dynamic phenomena, like the generation of high frequency oscillations. Fast-spiking interneurons, which represent mainly the parvalbumin-expressing, soma-targeting basket cells, are also implicated in pathological dynamics, like the propagation of seizures or the impaired coordination of activity in schizophrenia. In the present thesis, I investigate the role of fast-spiking interneurons in such dynamic phenomena by using computational and experimental techniques. First, I introduce a neural mass model of the neocortical microcircuit featuring divisive inhibition, a gain control mechanism, which is thought to be delivered mainly by the soma-targeting interneurons. Its dynamics were analysed at the onset of chaos and during the phenomena of entrainment and long-range synchronization. It is demonstrated that the mechanism of divisive inhibition reduces the sensitivity of the network to parameter changes and enhances the stability and exibility of oscillations. Next, in vitro electrophysiology was used to investigate the propagation of activity in the network of electrically coupled fast-spiking interneurons. Experimental evidence suggests that these interneurons and their gap junctions are involved in the propagation of seizures. Using multi-electrode array recordings and optogenetics, I investigated the possibility of such propagating activity under the conditions of raised extracellular K+ concentration which applies during seizures. Propagated activity was recorded and the involvement of gap junctions was con rmed by pharmacological manipulations. Finally, the interaction between two oscillations was investigated. Two oscillations with di erent frequencies were induced in cortical slices by directly activating the pyramidal cells using optogenetics. Their interaction suggested the possibility of a coincidence detection mechanism at the circuit level. Pharmacological manipulations were used to explore the role of the inhibitory interneurons during this phenomenon. The results, however, showed that the observed phenomenon was not a result of synaptic activity. Nevertheless, the experiments provided some insights about the excitability of the tissue through scattered light while using optogenetics. This investigation provides new insights into the role of fast-spiking interneurons in the neocortex. In particular, it is suggested that the gain control mechanism is important for the physiological oscillatory dynamics of the network and that the gap junctions between these interneurons can potentially contribute to the inhibitory restraint during a seizure.Wellcome Trust

Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise

The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB). The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min) of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha) binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies