Fernanda S. Matias

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.

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.

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.

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.

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.

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.

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.

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.

Anticipated synchronization in neuronal motifs

Anticipated synchronization (AS) is a counterintuitive stable dynamical regime discovered by Voss in the last decade [1]. It consists in the stable synchronized regime between two identical autonomous dynamical systems coupled (unidirectionally) in a master-slave (MS) configuration, if the slave also receives a negative delayed self-feedback. In such regime the slave predicts the master. Although AS has shown to be stable in a variety of theoretical studies [1-3] and in experimental observations [4] with semiconductor lasers and electronic circuits, studies in biological and neuronal systems are still lacking. The first verification of AS in neuronal models was done between two FitzHugh-Nagumo neurons coupled in a MS configuration with negative delayed self-feedback and driven by white noise [2]. In neuronal networks, AS means that the slave (post-synaptic) neuron can fire spikes right before the master (pre-synaptic) neuron. However the slave delayed self-feedback that induces the anticipated synchronization as suggested by Voss is unrealistic in neuronal circuitry. Recently, it has been shown that in a biologically plausible neuronal model, the self-feedback can be replaced by an inhibitory loop mediated by an interneuron and chemical synapses [5]. This master-slave-interneuron motif exhibits the usual delay synchronized (DS) regime for small values of the inhibitory synaptic conductance (g) as well as the AS regime for larger g. Moreover, the time delay between consecutive spikes of the master and the slave neurons is a function of the synaptic conductances. Both regimes were shown to be stable for a large set of parameters, different external currents, structural motif and neuron models [6]. Here we investigate the robustness of AS for others motifs, larger populations, neuronal heterogeneity and noise. In all the situations the transition from DS to AS is continuous and smooth.

Reconstructing the directionality of coupling between cortical populations with negative phase lag

Understanding how information is processed in the brain is one of the key areas in neuroscience research.Different tools have been employed to reconstruct directional influence and to infer the effective connectivity between distinct brain regions. Particularly, it has been shown [1] that in non-linear delay-coupled oscillating systems exhibiting a negative phase lag, Granger causality (GC) might not provide the correct direction of information flow (from the driver to the receiver). Such systems have been studied before in the theoretical framework of Anticipated Synchronization (AS) developed in the field of dynamical systems [2]. This counterintuitive synchronization regime can be a stable solution of two dynamical systems coupled in a master-slave (driver-receiver) configuration when the slave receives a negative delayed self-feedback. Recently, it has been shown that unidirectional coupled neuronal population models can also exhibit AS [3]. In these cortical like populations the delayed feedback has been replaced by a dynamical inhibitory loop mediated by interneurons. Here we show that in these biologically plausible models, GC provides the correct directionality of the coupling for both positive and negative phase differences. In fact, when compared to experimental data in the primate cortex our model reproduces experimental phase lags, coherence spectra and GC spectra [3].