Erratum: Self-consistent formulations for stochastic nonlinear neuronal dynamics [Phys. Rev. E 101, 042124 (2020)].

This corrects the article DOI: 10.1103/PhysRevE.101.042124.

NNMT: Mean-Field Based Analysis Tools for Neuronal Network Models.

Mean-field theory of neuronal networks has led to numerous advances in our analytical and intuitive understanding of their dynamics during the past decades. In order to make mean-field based analysis tools more accessible, we implemented an extensible, easy-to-use open-source Python toolbox that collects a variety of mean-field methods for the leaky integrate-and-fire neuron model. The Neuronal Network Mean-field Toolbox (NNMT) in its current state allows for estimating properties of large neuronal networks, such as firing rates, power spectra, and dynamical stability in mean-field and linear response approximation, without running simulations. In this article, we describe how the toolbox is implemented, show how it is used to reproduce results of previous studies, and discuss different use-cases, such as parameter space explorations, or mapping different network models. Although the initial version of the toolbox focuses on methods for leaky integrate-and-fire neurons, its structure is designed to be open and extensible. It aims to provide a platform for collecting analytical methods for neuronal network model analysis, such that the neuroscientific community can take maximal advantage of them.

Gell-Mann-Low Criticality in Neural Networks.

Criticality is deeply related to optimal computational capacity. The lack of a renormalized theory of critical brain dynamics, however, so far limits insights into this form of biological information processing to mean-field results. These methods neglect a key feature of critical systems: the interaction between degrees of freedom across all length scales, required for complex nonlinear computation. We present a renormalized theory of a prototypical neural field theory, the stochastic Wilson-Cowan equation. We compute the flow of couplings, which parametrize interactions on increasing length scales. Despite similarities with the Kardar-Parisi-Zhang model, the theory is of a Gell-Mann-Low type, the archetypal form of a renormalizable quantum field theory. Here, nonlinear couplings vanish, flowing towards the Gaussian fixed point, but logarithmically slowly, thus remaining effective on most scales. We show this critical structure of interactions to implement a desirable trade-off between linearity, optimal for information storage, and nonlinearity, required for computation.

Global organization of neuronal activity only requires unstructured local connectivity.

Modern electrophysiological recordings simultaneously capture single-unit spiking activities of hundreds of neurons spread across large cortical distances. Yet, this parallel activity is often confined to relatively low-dimensional manifolds. This implies strong coordination also among neurons that are most likely not even connected. Here, we combine in vivo recordings with network models and theory to characterize the nature of mesoscopic coordination patterns in macaque motor cortex and to expose their origin: We find that heterogeneity in local connectivity supports network states with complex long-range cooperation between neurons that arises from multi-synaptic, short-range connections. Our theory explains the experimentally observed spatial organization of covariances in resting state recordings as well as the behaviorally related modulation of covariance patterns during a reach-to-grasp task. The ubiquity of heterogeneity in local cortical circuits suggests that the brain uses the described mechanism to flexibly adapt neuronal coordination to momentary demands.

Large-Deviation Approach to Random Recurrent Neuronal Networks: Parameter Inference and Fluctuation-Induced Transitions.

We here unify the field-theoretical approach to neuronal networks with large deviations theory. For a prototypical random recurrent network model with continuous-valued units, we show that the effective action is identical to the rate function and derive the latter using field theory. This rate function takes the form of a Kullback-Leibler divergence which enables data-driven inference of model parameters and calculation of fluctuations beyond mean-field theory. Lastly, we expose a regime with fluctuation-induced transitions between mean-field solutions.

Event-Based Update of Synapses in Voltage-Based Learning Rules.

Due to the point-like nature of neuronal spiking, efficient neural network simulators often employ event-based simulation schemes for synapses. Yet many types of synaptic plasticity rely on the membrane potential of the postsynaptic cell as a third factor in addition to pre- and postsynaptic spike times. In some learning rules membrane potentials not only influence synaptic weight changes at the time points of spike events but in a continuous manner. In these cases, synapses therefore require information on the full time course of membrane potentials to update their strength which a priori suggests a continuous update in a time-driven manner. The latter hinders scaling of simulations to realistic cortical network sizes and relevant time scales for learning. Here, we derive two efficient algorithms for archiving postsynaptic membrane potentials, both compatible with modern simulation engines based on event-based synapse updates. We theoretically contrast the two algorithms with a time-driven synapse update scheme to analyze advantages in terms of memory and computations. We further present a reference implementation in the spiking neural network simulator NEST for two prototypical voltage-based plasticity rules: the Clopath rule and the Urbanczik-Senn rule. For both rules, the two event-based algorithms significantly outperform the time-driven scheme. Depending on the amount of data to be stored for plasticity, which heavily differs between the rules, a strong performance increase can be achieved by compressing or sampling of information on membrane potentials. Our results on computational efficiency related to archiving of information provide guidelines for the design of learning rules in order to make them practically usable in large-scale networks.

The covariance perceptron: A new paradigm for classification and processing of time series in recurrent neuronal networks.

Learning in neuronal networks has developed in many directions, in particular to reproduce cognitive tasks like image recognition and speech processing. Implementations have been inspired by stereotypical neuronal responses like tuning curves in the visual system, where, for example, ON/OFF cells fire or not depending on the contrast in their receptive fields. Classical models of neuronal networks therefore map a set of input signals to a set of activity levels in the output of the network. Each category of inputs is thereby predominantly characterized by its mean. In the case of time series, fluctuations around this mean constitute noise in this view. For this paradigm, the high variability exhibited by the cortical activity may thus imply limitations or constraints, which have been discussed for many years. For example, the need for averaging neuronal activity over long periods or large groups of cells to assess a robust mean and to diminish the effect of noise correlations. To reconcile robust computations with variable neuronal activity, we here propose a conceptual change of perspective by employing variability of activity as the basis for stimulus-related information to be learned by neurons, rather than merely being the noise that corrupts the mean signal. In this new paradigm both afferent and recurrent weights in a network are tuned to shape the input-output mapping for covariances, the second-order statistics of the fluctuating activity. When including time lags, covariance patterns define a natural metric for time series that capture their propagating nature. We develop the theory for classification of time series based on their spatio-temporal covariances, which reflect dynamical properties. We demonstrate that recurrent connectivity is able to transform information contained in the temporal structure of the signal into spatial covariances. Finally, we use the MNIST database to show how the covariance perceptron can capture specific second-order statistical patterns generated by moving digits.

Efficient Communication in Distributed Simulations of Spiking Neuronal Networks With Gap Junctions.

Investigating the dynamics and function of large-scale spiking neuronal networks with realistic numbers of synapses is made possible today by state-of-the-art simulation code that scales to the largest contemporary supercomputers. However, simulations that involve electrical interactions, also called gap junctions, besides chemical synapses scale only poorly due to a communication scheme that collects global data on each compute node. In comparison to chemical synapses, gap junctions are far less abundant. To improve scalability we exploit this sparsity by integrating an existing framework for continuous interactions with a recently proposed directed communication scheme for spikes. Using a reference implementation in the NEST simulator we demonstrate excellent scalability of the integrated framework, accelerating large-scale simulations with gap junctions by more than an order of magnitude. This allows, for the first time, the efficient exploration of the interactions of chemical and electrical coupling in large-scale neuronal networks models with natural synapse density distributed across thousands of compute nodes.

Self-consistent formulations for stochastic nonlinear neuronal dynamics.

Neural dynamics is often investigated with tools from bifurcation theory. However, many neuron models are stochastic, mimicking fluctuations in the input from unknown parts of the brain or the spiking nature of signals. Noise changes the dynamics with respect to the deterministic model; in particular classical bifurcation theory cannot be applied. We formulate the stochastic neuron dynamics in the Martin-Siggia-Rose de Dominicis-Janssen (MSRDJ) formalism and present the fluctuation expansion of the effective action and the functional renormalization group (fRG) as two systematic ways to incorporate corrections to the mean dynamics and time-dependent statistics due to fluctuations in the presence of nonlinear neuronal gain. To formulate self-consistency equations, we derive a fundamental link between the effective action in the Onsager-Machlup (OM) formalism, which allows the study of phase transitions, and the MSRDJ effective action, which is computationally advantageous. These results in particular allow the derivation of an OM effective action for systems with non-Gaussian noise. This approach naturally leads to effective deterministic equations for the first moment of the stochastic system; they explain how nonlinearities and noise cooperate to produce memory effects. Moreover, the MSRDJ formulation yields an effective linear system that has identical power spectra and linear response. Starting from the better known loopwise approximation, we then discuss the use of the fRG as a method to obtain self-consistency beyond the mean. We present a new efficient truncation scheme for the hierarchy of flow equations for the vertex functions by adapting the Blaizot, Méndez, and Wschebor approximation from the derivative expansion to the vertex expansion. The methods are presented by means of the simplest possible example of a stochastic differential equation that has generic features of neuronal dynamics.

Second type of criticality in the brain uncovers rich multiple-neuron dynamics.

Cortical networks that have been found to operate close to a critical point exhibit joint activations of large numbers of neurons. However, in motor cortex of the awake macaque monkey, we observe very different dynamics: massively parallel recordings of 155 single-neuron spiking activities show weak fluctuations on the population level. This a priori suggests that motor cortex operates in a noncritical regime, which in models, has been found to be suboptimal for computational performance. However, here, we show the opposite: The large dispersion of correlations across neurons is the signature of a second critical regime. This regime exhibits a rich dynamical repertoire hidden from macroscopic brain signals but essential for high performance in such concepts as reservoir computing. An analytical link between the eigenvalue spectrum of the dynamics, the heterogeneity of connectivity, and the dispersion of correlations allows us to assess the closeness to the critical point.

Corrigendum: Extremely Scalable Spiking Neuronal Network Simulation Code: From Laptops to Exascale Computers.

[This corrects the article DOI: 10.3389/fninf.2018.00002.].

Spectral bandwidth of interictal fast epileptic activity characterizes the seizure onset zone.

The foremost aim of presurgical epilepsy evaluation is the delineation of the seizure onset zone (SOZ). There is increasing evidence that fast epileptic activity (FEA, 14-250 Hz) occurring interictally, i.e. between seizures, is predominantly localized within the SOZ. Currently it is unknown, which frequency band of FEA performs best in identifying the SOZ, although prior studies suggest highest concordance of spectral changes with the SOZ for high frequency changes. We suspected that FEA reflects dampened oscillations in local cortical excitatory-inhibitory neural networks, and that interictal FEA in the SOZ is a consequence of reduced oscillatory damping. We therefore predict a narrowing of the spectral bandwidth alongside increased amplitudes of spectral peaks during interictal FEA events. To test this hypothesis, we evaluated spectral changes during interictal FEA in invasive EEG (iEEG) recordings of 13 patients with focal epilepsy. In relative spectra of beta and gamma band changes (14-250 Hz) during FEA, we found that spectral peaks within the SOZ indeed were significantly more narrow-banded and their power changes were significantly higher than outside the SOZ. In contrast, the peak frequency did not differ within and outside the SOZ. Our results show that bandwidth and power changes of spectral modulations during FEA both help localizing the SOZ. We propose the spectral bandwidth as new source of information for the evaluation of EEG data.

Extremely Scalable Spiking Neuronal Network Simulation Code: From Laptops to Exascale Computers.

State-of-the-art software tools for neuronal network simulations scale to the largest computing systems available today and enable investigations of large-scale networks of up to 10 % of the human cortex at a resolution of individual neurons and synapses. Due to an upper limit on the number of incoming connections of a single neuron, network connectivity becomes extremely sparse at this scale. To manage computational costs, simulation software ultimately targeting the brain scale needs to fully exploit this sparsity. Here we present a two-tier connection infrastructure and a framework for directed communication among compute nodes accounting for the sparsity of brain-scale networks. We demonstrate the feasibility of this approach by implementing the technology in the NEST simulation code and we investigate its performance in different scaling scenarios of typical network simulations. Our results show that the new data structures and communication scheme prepare the simulation kernel for post-petascale high-performance computing facilities without sacrificing performance in smaller systems.

The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG.

Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.

Computational Neuroscience: Mathematical and Statistical Perspectives.

Mathematical and statistical models have played important roles in neuroscience, especially by describing the electrical activity of neurons recorded individually, or collectively across large networks. As the field moves forward rapidly, new challenges are emerging. For maximal effectiveness, those working to advance computational neuroscience will need to appreciate and exploit the complementary strengths of mechanistic theory and the statistical paradigm.

Bistability, non-ergodicity, and inhibition in pairwise maximum-entropy models.

Pairwise maximum-entropy models have been used in neuroscience to predict the activity of neuronal populations, given only the time-averaged correlations of the neuron activities. This paper provides evidence that the pairwise model, applied to experimental recordings, would produce a bimodal distribution for the population-averaged activity, and for some population sizes the second mode would peak at high activities, that experimentally would be equivalent to 90% of the neuron population active within time-windows of few milliseconds. Several problems are connected with this bimodality: 1. The presence of the high-activity mode is unrealistic in view of observed neuronal activity and on neurobiological grounds. 2. Boltzmann learning becomes non-ergodic, hence the pairwise maximum-entropy distribution cannot be found: in fact, Boltzmann learning would produce an incorrect distribution; similarly, common variants of mean-field approximations also produce an incorrect distribution. 3. The Glauber dynamics associated with the model is unrealistically bistable and cannot be used to generate realistic surrogate data. This bimodality problem is first demonstrated for an experimental dataset from 159 neurons in the motor cortex of macaque monkey. Evidence is then provided that this problem affects typical neural recordings of population sizes of a couple of hundreds or more neurons. The cause of the bimodality problem is identified as the inability of standard maximum-entropy distributions with a uniform reference measure to model neuronal inhibition. To eliminate this problem a modified maximum-entropy model is presented, which reflects a basic effect of inhibition in the form of a simple but non-uniform reference measure. This model does not lead to unrealistic bimodalities, can be found with Boltzmann learning, and has an associated Glauber dynamics which incorporates a minimal asymmetric inhibition.

Locking of correlated neural activity to ongoing oscillations.

Population-wide oscillations are ubiquitously observed in mesoscopic signals of cortical activity. In these network states a global oscillatory cycle modulates the propensity of neurons to fire. Synchronous activation of neurons has been hypothesized to be a separate channel of signal processing information in the brain. A salient question is therefore if and how oscillations interact with spike synchrony and in how far these channels can be considered separate. Experiments indeed showed that correlated spiking co-modulates with the static firing rate and is also tightly locked to the phase of beta-oscillations. While the dependence of correlations on the mean rate is well understood in feed-forward networks, it remains unclear why and by which mechanisms correlations tightly lock to an oscillatory cycle. We here demonstrate that such correlated activation of pairs of neurons is qualitatively explained by periodically-driven random networks. We identify the mechanisms by which covariances depend on a driving periodic stimulus. Mean-field theory combined with linear response theory yields closed-form expressions for the cyclostationary mean activities and pairwise zero-time-lag covariances of binary recurrent random networks. Two distinct mechanisms cause time-dependent covariances: the modulation of the susceptibility of single neurons (via the external input and network feedback) and the time-varying variances of single unit activities. For some parameters, the effectively inhibitory recurrent feedback leads to resonant covariances even if mean activities show non-resonant behavior. Our analytical results open the question of time-modulated synchronous activity to a quantitative analysis.

Integration of Continuous-Time Dynamics in a Spiking Neural Network Simulator.

Contemporary modeling approaches to the dynamics of neural networks include two important classes of models: biologically grounded spiking neuron models and functionally inspired rate-based units. We present a unified simulation framework that supports the combination of the two for multi-scale modeling, enables the quantitative validation of mean-field approaches by spiking network simulations, and provides an increase in reliability by usage of the same simulation code and the same network model specifications for both model classes. While most spiking simulations rely on the communication of discrete events, rate models require time-continuous interactions between neurons. Exploiting the conceptual similarity to the inclusion of gap junctions in spiking network simulations, we arrive at a reference implementation of instantaneous and delayed interactions between rate-based models in a spiking network simulator. The separation of rate dynamics from the general connection and communication infrastructure ensures flexibility of the framework. In addition to the standard implementation we present an iterative approach based on waveform-relaxation techniques to reduce communication and increase performance for large-scale simulations of rate-based models with instantaneous interactions. Finally we demonstrate the broad applicability of the framework by considering various examples from the literature, ranging from random networks to neural-field models. The study provides the prerequisite for interactions between rate-based and spiking models in a joint simulation.

Fundamental Activity Constraints Lead to Specific Interpretations of the Connectome.

The continuous integration of experimental data into coherent models of the brain is an increasing challenge of modern neuroscience. Such models provide a bridge between structure and activity, and identify the mechanisms giving rise to experimental observations. Nevertheless, structurally realistic network models of spiking neurons are necessarily underconstrained even if experimental data on brain connectivity are incorporated to the best of our knowledge. Guided by physiological observations, any model must therefore explore the parameter ranges within the uncertainty of the data. Based on simulation results alone, however, the mechanisms underlying stable and physiologically realistic activity often remain obscure. We here employ a mean-field reduction of the dynamics, which allows us to include activity constraints into the process of model construction. We shape the phase space of a multi-scale network model of the vision-related areas of macaque cortex by systematically refining its connectivity. Fundamental constraints on the activity, i.e., prohibiting quiescence and requiring global stability, prove sufficient to obtain realistic layer- and area-specific activity. Only small adaptations of the structure are required, showing that the network operates close to an instability. The procedure identifies components of the network critical to its collective dynamics and creates hypotheses for structural data and future experiments. The method can be applied to networks involving any neuron model with a known gain function.

Perfect Detection of Spikes in the Linear Sub-threshold Dynamics of Point Neurons.

Spiking neuronal networks are usually simulated with one of three main schemes: the classical time-driven and event-driven schemes, and the more recent hybrid scheme. All three schemes evolve the state of a neuron through a series of checkpoints: equally spaced in the first scheme and determined neuron-wise by spike events in the latter two. The time-driven and the hybrid scheme determine whether the membrane potential of a neuron crosses a threshold at the end of the time interval between consecutive checkpoints. Threshold crossing can, however, occur within the interval even if this test is negative. Spikes can therefore be missed. The present work offers an alternative geometric point of view on neuronal dynamics, and derives, implements, and benchmarks a method for perfect retrospective spike detection. This method can be applied to neuron models with affine or linear subthreshold dynamics. The idea behind the method is to propagate the threshold with a time-inverted dynamics, testing whether the threshold crosses the neuron state to be evolved, rather than vice versa. Algebraically this translates into a set of inequalities necessary and sufficient for threshold crossing. This test is slower than the imperfect one, but can be optimized in several ways. Comparison confirms earlier results that the imperfect tests rarely miss spikes (less than a fraction 1/108 of missed spikes) in biologically relevant settings.