Mechanisms underlying reshuffling of visual responses by optogenetic stimulation in mice and monkeys.

The ability to optogenetically perturb neural circuits opens an unprecedented window into mechanisms governing circuit function. We analyzed and theoretically modeled neuronal responses to visual and optogenetic inputs in mouse and monkey V1. In both species, optogenetic stimulation of excitatory neurons strongly modulated the activity of single neurons yet had weak or no effects on the distribution of firing rates across the population. Thus, the optogenetic inputs reshuffled firing rates across the network. Key statistics of mouse and monkey responses lay on a continuum, with mice/monkeys occupying the low-/high-rate regions, respectively. We show that neuronal reshuffling emerges generically in randomly connected excitatory/inhibitory networks, provided the coupling strength (combination of recurrent coupling and external input) is sufficient that powerful inhibitory feedback cancels the mean optogenetic input. A more realistic model, distinguishing tuned visual vs. untuned optogenetic input in a structured network, reduces the coupling strength needed to explain reshuffling.

Interrogating theoretical models of neural computation with emergent property inference.

A cornerstone of theoretical neuroscience is the circuit model: a system of equations that captures a hypothesized neural mechanism. Such models are valuable when they give rise to an experimentally observed phenomenon -- whether behavioral or a pattern of neural activity -- and thus can offer insights into neural computation. The operation of these circuits, like all models, critically depends on the choice of model parameters. A key step is then to identify the model parameters consistent with observed phenomena: to solve the inverse problem. In this work, we present a novel technique, emergent property inference (EPI), that brings the modern probabilistic modeling toolkit to theoretical neuroscience. When theorizing circuit models, theoreticians predominantly focus on reproducing computational properties rather than a particular dataset. Our method uses deep neural networks to learn parameter distributions with these computational properties. This methodology is introduced through a motivational example of parameter inference in the stomatogastric ganglion. EPI is then shown to allow precise control over the behavior of inferred parameters and to scale in parameter dimension better than alternative techniques. In the remainder of this work, we present novel theoretical findings in models of primary visual cortex and superior colliculus, which were gained through the examination of complex parametric structure captured by EPI. Beyond its scientific contribution, this work illustrates the variety of analyses possible once deep learning is harnessed towards solving theoretical inverse problems.

Flexible information routing by transient synchrony.

Perception, cognition and behavior rely on flexible communication between microcircuits in distinct cortical regions. The mechanisms underlying rapid information rerouting between such microcircuits are still unknown. It has been proposed that changing patterns of coherence between local gamma rhythms support flexible information rerouting. The stochastic and transient nature of gamma oscillations in vivo, however, is hard to reconcile with such a function. Here we show that models of cortical circuits near the onset of oscillatory synchrony selectively route input signals despite the short duration of gamma bursts and the irregularity of neuronal firing. In canonical multiarea circuits, we find that gamma bursts spontaneously arise with matched timing and frequency and that they organize information flow by large-scale routing states. Specific self-organized routing states can be induced by minor modulations of background activity.

Controlling the oscillation phase through precisely timed closed-loop optogenetic stimulation: a computational study.

Dynamic oscillatory coherence is believed to play a central role in flexible communication between brain circuits. To test this communication-through-coherence hypothesis, experimental protocols that allow a reliable control of phase-relations between neuronal populations are needed. In this modeling study, we explore the potential of closed-loop optogenetic stimulation for the control of functional interactions mediated by oscillatory coherence. The theory of non-linear oscillators predicts that the efficacy of local stimulation will depend not only on the stimulation intensity but also on its timing relative to the ongoing oscillation in the target area. Induced phase-shifts are expected to be stronger when the stimulation is applied within specific narrow phase intervals. Conversely, stimulations with the same or even stronger intensity are less effective when timed randomly. Stimulation should thus be properly phased with respect to ongoing oscillations (in order to optimally perturb them) and the timing of the stimulation onset must be determined by a real-time phase analysis of simultaneously recorded local field potentials (LFPs). Here, we introduce an electrophysiologically calibrated model of Channelrhodopsin 2 (ChR2)-induced photocurrents, based on fits holding over two decades of light intensity. Through simulations of a neural population which undergoes coherent gamma oscillations-either spontaneously or as an effect of continuous optogenetic driving-we show that precisely-timed photostimulation pulses can be used to shift the phase of oscillation, even at transduction rates smaller than 25%. We consider then a canonic circuit with two inter-connected neural populations oscillating with gamma frequency in a phase-locked manner. We demonstrate that photostimulation pulses applied locally to a single population can induce, if precisely phased, a lasting reorganization of the phase-locking pattern and hence modify functional interactions between the two populations.

Análisis complejo de la actividad eléctrica en la epilepsia del lóbulo temporal: registros electrocorticográficos / Significance of complex analysis of electrical activity in temporal lobe epilepsy: electrocorticography

Introducción. La localización y escisión de las zonas epileptógenas es el tratamiento tradicional en la epilepsia del lóbulo temporal farmacorresistente. No obstante, algunos pacientes persisten con crisis después de la cirugía. Por lo tanto, deben formularse nuevas hipótesis a efectos de explicar los aparentes fallos en las cirugías correctamente realizadas.Objetivo. Por medio de una aproximación no tradicional en el campo, como es el uso de redes complejas, se trata de mostrar que la modificación de las propiedades de la red límbica puede originar la eliminación de las crisis, independientemente de la localización de las zonas epileptógenas. Pacientes y métodos. Se han empleado los registros electrocorticográficos intraoperatorios de 20 pacientes con epilepsia del lóbulo temporal farmacorresistente. Por medio de un análisis de redes complejas, se ha estudiado la actividad desincronización local en corteza lateral y mesial del lóbulo temporal y, fundamentalmente, se han determinado las zonas de mayor estabilidad temporal. Resultados. Aquellas zonas corticales de mayor actividad sincrónica se asocian a una mayor estabilidad temporal, y cuando estas zonas son resecadas durante la cirugía, el paciente no vuelve a sufrir crisis discapacitantes. Por el contrario,cuando estas zonas no son resecadas, el paciente continúa con crisis postoperatorias. Conclusiones. Los resultados apoyan la hipótesis de la existencia de una red límbica, de la cual las cortezas lateral y mesial del lóbulo temporal forman parte, y cuya capacidad de establecer una sincronización global se ve afectada cuando se eliminan ciertas zonas (AU)

Introduction. Locating and excising epileptogenic zones is the traditional treatment in pharmacoresistant temporal lobeepilepsy. Some patients, however, continue to suffer from attacks even after surgery. Therefore, new hypotheses must be formulated in order to account for the apparent shortcomings of correctly performed surgical procedures.Aims. An approach that is not traditional in the field, namely complex networks, is used to attempt to show that modifyingthe properties of the limbic network can lead to the elimination of the attacks, regardless of the location of the epileptogenic zones.Patients and methods. The intraoperative electrocorticographic recordings of 20 patients with pharmacoresistant temporallobe epilepsy were utilised in the study. An analysis of complex networks was used to study the local synchronisation activity in the lateral and mesial cortex of the temporal lobe and, essentially, the zones with the highest temporal stability were determined.Results. Those cortical zones with higher synchronic activity are associated with a greater temporal stability and when these zones are excised during surgery, the patient no longer suffers any disabling attacks. In contrast, when these zones are not excised, the patient continues to have attacks in the post-operative period. Conclusions. The findings support the hypothesis of the existence of a limbic network, which the lateral and mesial corticesof the temporal lobe are part of, and whose capacity to establish an overall synchronisation is affected when certain zones are removed (AU)

[Significance of complex analysis of electrical activity in temporal lobe epilepsy: electrocorticography]. / Analisis complejo de la actividad electrica en la epilepsia del lobulo temporal: registros electrocorticograficos.

INTRODUCTION: Locating and excising epileptogenic zones is the traditional treatment in pharmacoresistant temporal lobe epilepsy. Some patients, however, continue to suffer from attacks even after surgery. Therefore, new hypotheses must be formulated in order to account for the apparent shortcomings of correctly performed surgical procedures. AIMS: An approach that is not traditional in the field, namely complex networks, is used to attempt to show that modifying the properties of the limbic network can lead to the elimination of the attacks, regardless of the location of the epileptogenic zones. PATIENTS AND METHODS: The intraoperative electrocorticographic recordings of 20 patients with pharmacoresistant temporal lobe epilepsy were utilised in the study. An analysis of complex networks was used to study the local synchronisation activity in the lateral and mesial cortex of the temporal lobe and, essentially, the zones with the highest temporal stability were determined. RESULTS: Those cortical zones with higher synchronic activity are associated with a greater temporal stability and when these zones are excised during surgery, the patient no longer suffers any disabling attacks. In contrast, when these zones are not excised, the patient continues to have attacks in the post-operative period. CONCLUSIONS: The findings support the hypothesis of the existence of a limbic network, which the lateral and mesial cortices of the temporal lobe are part of, and whose capacity to establish an overall synchronisation is affected when certain zones are removed.

Stability of synchronization clusters and seizurability in temporal lobe epilepsy.

PURPOSE: Identification of critical areas in presurgical evaluations of patients with temporal lobe epilepsy is the most important step prior to resection. According to the "epileptic focus model", localization of seizure onset zones is the main task to be accomplished. Nevertheless, a significant minority of epileptic patients continue to experience seizures after surgery (even when the focus is correctly located), an observation that is difficult to explain under this approach. However, if attention is shifted from a specific cortical location toward the network properties themselves, then the epileptic network model does allow us to explain unsuccessful surgical outcomes. METHODS: The intraoperative electrocorticography records of 20 patients with temporal lobe epilepsy were analyzed in search of interictal synchronization clusters. Synchronization was analyzed, and the stability of highly synchronized areas was quantified. Surrogate data were constructed and used to statistically validate the results. Our results show the existence of highly localized and stable synchronization areas in both the lateral and the mesial areas of the temporal lobe ipsilateral to the clinical seizures. Synchronization areas seem to play a central role in the capacity of the epileptic network to generate clinical seizures. Resection of stable synchronization areas is associated with elimination of seizures; nonresection of synchronization clusters is associated with the persistence of seizures after surgery. DISCUSSION: We suggest that synchronization clusters and their stability play a central role in the epileptic network, favoring seizure onset and propagation. We further speculate that the stability distribution of these synchronization areas would differentiate normal from pathologic cases.