Feedforward and feedback influences through distinct frequency bands between two spiking-neuron networks.

Several studies on brain signals suggested that bottom-up and top-down influences are exerted through distinct frequency bands among visual cortical areas. It was recently shown that theta and gamma rhythms subserve feedforward, whereas the feedback influence is dominated by the alpha-beta rhythm in primates. A few theoretical models for reproducing these effects have been proposed so far. Here we show that a simple but biophysically plausible two-network motif composed of spiking-neuron models and chemical synapses can exhibit feedforward and feedback influences through distinct frequency bands. Different from previous studies, this kind of model allows us to study directed influences not only at the population level, by using a proxy for the local field potential, but also at the cellular level, by using the neuronal spiking series.

Neuronal heterogeneity modulates phase synchronization between unidirectionally coupled populations with excitation-inhibition balance.

Several experiments and models have highlighted the importance of neuronal heterogeneity in brain dynamics and function. However, how such a cell-to-cell diversity can affect cortical computation, synchronization, and neuronal communication is still under debate. Previous studies have focused on the effect of neuronal heterogeneity in one neuronal population. Here we are specifically interested in the effect of neuronal variability on the phase relations between two populations, which can be related to different cortical communication hypotheses. It has been recently shown that two spiking neuron populations unidirectionally connected in a sender-receiver configuration can exhibit anticipated synchronization (AS), which is characterized by a negative phase lag. This phenomenon has been reported in electrophysiological data of nonhuman primates and human EEG during a visual discrimination cognitive task. In experiments, the unidirectional coupling could be accessed by Granger causality and can be accompanied by either positive or negative phase difference between cortical areas. Here we propose a model of two coupled populations in which the neuronal heterogeneity can determine the dynamical relation between the sender and the receiver and can reproduce phase relations reported in experiments. Depending on the distribution of parameters characterizing the neuronal firing patterns, the system can exhibit both AS and the usual delayed synchronization regime (DS, with positive phase) as well as a zero-lag synchronization regime and phase bistability between AS and DS. Furthermore, we show that our network can present diversity in their phase relations maintaining the excitation-inhibition balance.

Statistical complexity is maximized close to criticality in cortical dynamics.

Complex systems are typically characterized as an intermediate situation between a complete regular structure and a random system. Brain signals can be studied as a striking example of such systems: cortical states can range from highly synchronous and ordered neuronal activity (with higher spiking variability) to desynchronized and disordered regimes (with lower spiking variability). It has been recently shown, by testing independent signatures of criticality, that a phase transition occurs in a cortical state of intermediate spiking variability. Here we use a symbolic information approach to show that, despite the monotonical increase of the Shannon entropy between ordered and disordered regimes, we can determine an intermediate state of maximum complexity based on the Jensen disequilibrium measure. More specifically, we show that statistical complexity is maximized close to criticality for cortical spiking data of urethane-anesthetized rats, as well as for a network model of excitable elements that presents a critical point of a nonequilibrium phase transition.

Anticipated synchronization in human EEG data: Unidirectional causality with negative phase lag.

Understanding the functional connectivity of the brain has become a major goal of neuroscience. In many situations the relative phase difference, together with coherence patterns, has been employed to infer the direction of the information flow. However, it has been recently shown in local field potential data from monkeys the existence of a synchronized regime in which unidirectionally coupled areas can present both positive and negative phase differences. During the counterintuitive regime, called anticipated synchronization (AS), the phase difference does not reflect the causality. Here we investigate coherence and causality at the alpha frequency band (f∼10 Hz) between pairs of electroencephalogram (EEG) electrodes in humans during a GO/NO-GO task. We show that human EEG signals can exhibit anticipated synchronization, which is characterized by a unidirectional influence from an electrode A to an electrode B, but the electrode B leads the electrode A in time. To the best of our knowledge, this is the first verification of AS in EEG signals and in the human brain. The usual delayed synchronization (DS) regime is also present between many pairs. DS is characterized by a unidirectional influence from an electrode A to an electrode B and a positive phase difference between A and B which indicates that the electrode A leads the electrode B in time. Moreover we show that EEG signals exhibit diversity in the phase relations: the pairs of electrodes can present in-phase, antiphase, or out-of-phase synchronization with a similar distribution of positive and negative phase differences.

Inferring correlations associated to causal interactions in brain signals using autoregressive models.

The specific connectivity of a neuronal network is reflected in the dynamics of the signals recorded on its nodes. The analysis of how the activity in one node predicts the behaviour of another gives the directionality in their relationship. However, each node is composed of many different elements which define the properties of the links. For instance, excitatory and inhibitory neuronal subtypes determine the functionality of the connection. Classic indexes such as the Granger causality (GC) quantifies these interactions, but they do not infer into the mechanism behind them. Here, we introduce an extension of the well-known GC that analyses the correlation associated to the specific influence that a transmitter node has over the receiver. This way, the G-causal link has a positive or negative effect if the predicted activity follows directly or inversely, respectively, the dynamics of the sender. The method is validated in a neuronal population model, testing the paradigm that excitatory and inhibitory neurons have a differential effect in the connectivity. Our approach correctly infers the positive or negative coupling produced by different types of neurons. Our results suggest that the proposed approach provides additional information on the characterization of G-causal connections, which is potentially relevant when it comes to understanding interactions in the brain circuits.

Exploring the Phase-Locking Mechanisms Yielding Delayed and Anticipated Synchronization in Neuronal Circuits.

Synchronization is one of the brain mechanisms allowing the coordination of neuronal activity required in many cognitive tasks. Anticipated Synchronization (AS) is a specific type of out-of-phase synchronization that occurs when two systems are unidirectionally coupled and, consequently, the information is transmitted from the sender to the receiver, but the receiver leads the sender in time. It has been shown that the primate cortex could operate in a regime of AS as part of normal neurocognitive function. However it is still unclear what is the mechanism that gives rise to anticipated synchronization in neuronal motifs. Here, we investigate the synchronization properties of cortical motifs on multiple scales and show that the internal dynamics of the receiver, which is related to its free running frequency in the uncoupled situation, is the main ingredient for AS to occur. For biologically plausible parameters, including excitation/inhibition balance, we found that the phase difference between the sender and the receiver decreases when the free running frequency of the receiver increases. As a consequence, the system switches from the usual delayed synchronization (DS) regime to an AS regime. We show that at three different scales, neuronal microcircuits, spiking neuronal populations and neural mass models, both the inhibitory loop and the external current acting on the receiver mediate the DS-AS transition for the sender-receiver configuration by changing the free running frequency of the receiver. Therefore, we propose that a faster internal dynamics of the receiver system is the main mechanism underlying anticipated synchronization in brain circuits.

Inhibitory autapse mediates anticipated synchronization between coupled neurons.

Two identical autonomous dynamical systems unidirectionally coupled in a sender-receiver configuration can exhibit anticipated synchronization (AS) if the receiver neuron also receives a delayed negative self-feedback. Recently, AS was shown to occur in a three-neuron motif with standard chemical synapses where the delayed inhibition was provided by an interneuron. Here, we show that a two-neuron model in the presence of an inhibitory autapse, which is a massive self-innervation present in the cortical architecture, may present AS. The GABAergic autapse regulates the internal dynamics of the receiver neuron and acts as the negative delayed self-feedback required by dynamical systems in order to exhibit AS. In this biologically plausible scenario, a smooth transition from the usual delayed synchronization (DS) to AS typically occurs when the inhibitory conductance is increased. The phenomenon is shown to be robust when model parameters are varied within a physiological range. For extremely large values of the inhibitory autapse the system undergoes to a phase-drift regime in which the receiver is faster than the sender. Furthermore, we show that the inhibitory autapse promotes a faster internal dynamics of the free-running Receiver when the two neurons are uncoupled, which could be the mechanism underlying anticipated synchronization and the DS-AS transition.

Anticipated and zero-lag synchronization in motifs of delay-coupled systems.

Anticipated and zero-lag synchronization have been observed in different scientific fields. In the brain, they might play a fundamental role in information processing, temporal coding and spatial attention. Recent numerical work on anticipated and zero-lag synchronization studied the role of delays. However, an analytical understanding of the conditions for these phenomena remains elusive. In this paper, we study both phenomena in systems with small delays. By performing a phase reduction and studying phase locked solutions, we uncover the functional relation between the delay, excitation and inhibition for the onset of anticipated synchronization in a sender-receiver-interneuron motif. In the case of zero-lag synchronization in a chain motif, we determine the stability conditions. These analytical solutions provide an excellent prediction of the phase-locked regimes of Hodgkin-Huxley models and Roessler oscillators.

Anticipated synchronization in neuronal circuits unveiled by a phase-response-curve analysis.

Anticipated synchronization (AS) is a counterintuitive behavior that has been observed in several systems. When AS occurs in a sender-receiver configuration, the latter can predict the future dynamics of the former for certain parameter values. In particular, in neuroscience AS was proposed to explain the apparent discrepancy between information flow and time lag in the cortical activity recorded in monkeys. Despite its success, a clear understanding of the mechanisms yielding AS in neuronal circuits is still missing. Here we use the well-known phase-response-curve (PRC) approach to study the prototypical sender-receiver-interneuron neuronal motif. Our aim is to better understand how the transitions between delayed to anticipated synchronization and anticipated synchronization to phase-drift regimes occur. We construct a map based on the PRC method to predict the phase-locking regimes and their stability. We find that a PRC function of two variables, accounting simultaneously for the inputs from sender and interneuron into the receiver, is essential to reproduce the numerical results obtained using a Hodgkin-Huxley model for the neurons. On the contrary, the typical approximation that considers a sum of two independent single-variable PRCs fails for intermediate to high values of the inhibitory coupling strength of the interneuron. In particular, it loses the delayed-synchronization to anticipated-synchronization transition.

On the role of the entorhinal cortex in the effective connectivity of the hippocampal formation.

Inferring effective connectivity from neurophysiological data is a challenging task. In particular, only a finite (and usually small) number of sites are simultaneously recorded, while the response of one of these sites can be influenced by other sites that are not being recorded. In the hippocampal formation, for instance, the connections between areas CA1-CA3, the dentate gyrus (DG), and the entorhinal cortex (EC) are well established. However, little is known about the relations within the EC layers, which might strongly affect the resulting effective connectivity estimations. In this work, we build excitatory/inhibitory neuronal populations representing the four areas CA1, CA3, the DG, and the EC and fix their connectivities. We model the EC by three layers (LII, LIII, and LV) and assume any possible connection between them. Our results, based on Granger Causality (GC) and Partial Transfer Entropy (PTE) measurements, reveal that the estimation of effective connectivity in the hippocampus strongly depends on the connectivities between EC layers. Moreover, we find, for certain EC configurations, very different results when comparing GC and PTE measurements. We further demonstrate that causal links can be robustly inferred regardless of the excitatory or inhibitory nature of the connection, adding complexity to their interpretation. Overall, our work highlights the importance of a careful analysis of the connectivity methods to prevent unrealistic conclusions when only partial information about the experimental system is available, as usually happens in brain networks. Our results suggest that the combination of causality measures with neuronal modeling based on precise neuroanatomical tracing may provide a powerful framework to disambiguate causal interactions in the brain.

Inhibitory loop robustly induces anticipated synchronization in neuronal microcircuits.

We investigate the synchronization properties between two excitatory coupled neurons in the presence of an inhibitory loop mediated by an interneuron. Dynamic inhibition together with noise independently applied to each neuron provide phase diversity in the dynamics of the neuronal motif. We show that the interplay between the coupling strengths and the external noise controls the phase relations between the neurons in a counterintuitive way. For a master-slave configuration (unidirectional coupling) we find that the slave can anticipate the master, on average, if the slave is subject to the inhibitory feedback. In this nonusual regime, called anticipated synchronization (AS), the phase of the postsynaptic neuron is advanced with respect to that of the presynaptic neuron. We also show that the AS regime survives even in the presence of unbalanced bidirectional excitatory coupling. Moreover, for the symmetric mutually coupled situation, the neuron that is subject to the inhibitory loop leads in phase.

A symbolic information approach to determine anticipated and delayed synchronization in neuronal circuit models.

The phenomenon of synchronization between two or more areas of the brain coupled asymmetrically is a relevant issue for understanding mechanisms and functions within the cerebral cortex. Anticipated synchronization (AS) refers to the situation in which the receiver system synchronizes to the future dynamics of the sender system while the intuitively expected delayed synchronization (DS) represents exactly the opposite case. AS and DS are investigated in the context of causal information formalism. More specifically, we use a multi-scale symbolic information-theory approach for discriminating the time delay displayed between two areas of the brain when they exchange information.

Self-Organized Near-Zero-Lag Synchronization Induced by Spike-Timing Dependent Plasticity in Cortical Populations.

Several cognitive tasks related to learning and memory exhibit synchronization of macroscopic cortical areas together with synaptic plasticity at neuronal level. Therefore, there is a growing effort among computational neuroscientists to understand the underlying mechanisms relating synchrony and plasticity in the brain. Here we numerically study the interplay between spike-timing dependent plasticity (STDP) and anticipated synchronization (AS). AS emerges when a dominant flux of information from one area to another is accompanied by a negative time lag (or phase). This means that the receiver region pulses before the sender does. In this paper we study the interplay between different synchronization regimes and STDP at the level of three-neuron microcircuits as well as cortical populations. We show that STDP can promote auto-organized zero-lag synchronization in unidirectionally coupled neuronal populations. We also find synchronization regimes with negative phase difference (AS) that are stable against plasticity. Finally, we show that the interplay between negative phase difference and STDP provides limited synaptic weight distribution without the need of imposing artificial boundaries.

Modeling positive Granger causality and negative phase lag between cortical areas.

Different measures of directional influence have been employed to infer effective connectivity in the brain. When the connectivity between two regions is such that one of them (the sender) strongly influences the other (the receiver), a positive phase lag is often expected. The assumption is that the time difference implicit in the relative phase reflects the transmission time of neuronal activity. However, Brovelli et al. (2004) observed that, in monkeys engaged in processing a cognitive task, a dominant directional influence from one area of sensorimotor cortex to another may be accompanied by either a negative or a positive time delay. Here we present a model of two brain regions, coupled with a well-defined directional influence, that displays similar features to those observed in the experimental data. This model is inspired by the theoretical framework of Anticipated Synchronization developed in the field of dynamical systems. Anticipated Synchronization is a form of synchronization that occurs when a unidirectional influence is transmitted from a sender to a receiver, but the receiver leads the sender in time. This counterintuitive synchronization regime can be a stable solution of two dynamical systems coupled in a master-slave (sender-receiver) configuration when the slave receives a negative delayed self-feedback. Despite efforts to understand the dynamics of Anticipated Synchronization, experimental evidence for it in the brain has been lacking. By reproducing experimental delay times and coherence spectra, our results provide a theoretical basis for the underlying mechanisms of the observed dynamics, and suggest that the primate cortex could operate in a regime of Anticipated Synchronization as part of normal neurocognitive function.

Anticipated synchronization in a biologically plausible model of neuronal motifs.

Two identical autonomous dynamical systems coupled in a master-slave configuration can exhibit anticipated synchronization (AS) if the slave also receives a delayed negative self-feedback. Recently, AS was shown to occur in systems of simplified neuron models, requiring the coupling of the neuronal membrane potential with its delayed value. However, this coupling has no obvious biological correlate. Here we propose a canonical neuronal microcircuit with standard chemical synapses, where the delayed inhibition is provided by an interneuron. In this biologically plausible scenario, a smooth transition from delayed synchronization (DS) to AS typically occurs when the inhibitory synaptic conductance is increased. The phenomenon is shown to be robust when model parameters are varied within a physiological range. Since the DS-AS transition amounts to an inversion in the timing of the pre- and post-synaptic spikes, our results could have a bearing on spike-timing-dependent plasticity models.