Detection and categorization of severe cardiac disorders based solely on heart period measurements.

Cardiac disorders are common conditions associated with a high mortality rate. Due to their potential for causing serious symptoms, it is desirable to constantly monitor cardiac status using an accessible device such as a smartwatch. While electrocardiograms (ECGs) can make the detailed diagnosis of cardiac disorders, the examination is typically performed only once a year for each individual during health checkups, and it requires expert medical practitioners to make comprehensive judgments. Here we describe a newly developed automated system for alerting individuals about cardiac disorders solely by measuring a series of heart periods. For this purpose, we examined two metrics of heart rate variability (HRV) and analyzed 1-day ECG recordings of more than 1,000 subjects in total. We found that a metric of local variation was more efficient than conventional HRV metrics for alerting cardiac disorders, and furthermore, that a newly introduced metric of local-global variation resulted in superior capacity for discriminating between premature contraction and atrial fibrillation. Even with a 1-minute recording of heart periods, our new detection system had a diagnostic performance even better than that of the conventional analysis method applied to a 1-day recording.

A convolutional neural network for estimating synaptic connectivity from spike trains.

The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset. Here we present another method using a Convolutional Neural Network for Estimating synaptic Connectivity from spike trains. After adaptation to huge amounts of simulated data, this method robustly captures the specific feature of monosynaptic impact in a noisy cross-correlogram. There are no user-adjustable parameters. With this new method, we have constructed diagrams of neuronal circuits recorded in several cortical areas of monkeys.

Estimating the time-varying reproduction number of COVID-19 with a state-space method.

After slowing down the spread of the novel coronavirus COVID-19, many countries have started to relax their confinement measures in the face of critical damage to socioeconomic structures. At this stage, it is desirable to monitor the degree to which political measures or social affairs have exerted influence on the spread of disease. Though it is difficult to trace back individual transmission of infections whose incubation periods are long and highly variable, estimating the average spreading rate is possible if a proper mathematical model can be devised to analyze daily event-occurrences. To render an accurate assessment, we have devised a state-space method for fitting a discrete-time variant of the Hawkes process to a given dataset of daily confirmed cases. The proposed method detects changes occurring in each country and assesses the impact of social events in terms of the temporally varying reproduction number, which corresponds to the average number of cases directly caused by a single infected case. Moreover, the proposed method can be used to predict the possible consequences of alternative political measures. This information can serve as a reference for behavioral guidelines that should be adopted according to the varying risk of infection.

Improved hyperacuity estimation of spike timing from calcium imaging.

Two-photon imaging is a major recording technique used in neuroscience. However, it suffers from several limitations, including a low sampling rate, the nonlinearity of calcium responses, the slow dynamics of calcium dyes and a low SNR, all of which severely limit the potential of two-photon imaging to elucidate neuronal dynamics with high temporal resolution. We developed a hyperacuity algorithm (HA_time) based on an approach that combines a generative model and machine learning to improve spike detection and the precision of spike time inference. Bayesian inference was performed to estimate the calcium spike model, assuming constant spike shape and size. A support vector machine using this information and a jittering method maximizing the likelihood of estimated spike times enhanced spike time estimation precision approximately fourfold (range, 2-7; mean, 3.5-4.0; 2SEM, 0.1-0.25) compared to the sampling interval. Benchmark scores of HA_time for biological data from three different brain regions were among the best of the benchmark algorithms. Simulation of broader data conditions indicated that our algorithm performed better than others with high firing rate conditions. Furthermore, HA_time exhibited comparable performance for conditions with and without ground truths. Thus HA_time is a useful tool for spike reconstruction from two-photon imaging.

Reconstructing neuronal circuitry from parallel spike trains.

State-of-the-art techniques allow researchers to record large numbers of spike trains in parallel for many hours. With enough such data, we should be able to infer the connectivity among neurons. Here we develop a method for reconstructing neuronal circuitry by applying a generalized linear model (GLM) to spike cross-correlations. Our method estimates connections between neurons in units of postsynaptic potentials and the amount of spike recordings needed to verify connections. The performance of inference is optimized by counting the estimation errors using synthetic data. This method is superior to other established methods in correctly estimating connectivity. By applying our method to rat hippocampal data, we show that the types of estimated connections match the results inferred from other physiological cues. Thus our method provides the means to build a circuit diagram from recorded spike trains, thereby providing a basis for elucidating the differences in information processing in different brain regions.

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.

Correlations and forecast of death tolls in the Syrian conflict.

The Syrian armed conflict has been ongoing since 2011 and has already caused thousands of deaths. The analysis of death tolls helps to understand the dynamics of the conflict and to better allocate resources and aid to the affected areas. In this article, we use information on the daily number of deaths to study temporal and spatial correlations in the data, and exploit this information to forecast events of deaths. We found that the number of violent deaths per day in Syria varies more widely than that in England in which non-violent deaths dominate. We have identified strong positive auto-correlations in Syrian cities and non-trivial cross-correlations across some of them. The results indicate synchronization in the number of deaths at different times and locations, suggesting respectively that local attacks are followed by more attacks at subsequent days and that coordinated attacks may also take place across different locations. Thus the analysis of high temporal resolution data across multiple cities makes it possible to infer attack strategies, warn potential occurrence of future events, and hopefully avoid further deaths.

Emergence of event cascades in inhomogeneous networks.

There is a commonality among contagious diseases, tweets, and neuronal firings that past events facilitate the future occurrence of events. The spread of events has been extensively studied such that the systems exhibit catastrophic chain reactions if the interaction represented by the ratio of reproduction exceeds unity; however, their subthreshold states are not fully understood. Here, we report that these systems are possessed by nonstationary cascades of event-occurrences already in the subthreshold regime. Event cascades can be harmful in some contexts, when the peak-demand causes vaccine shortages, heavy traffic on communication lines, but may be beneficial in other contexts, such that spontaneous activity in neural networks may be used to generate motion or store memory. Thus it is important to comprehend the mechanism by which such cascades appear, and consider controlling a system to tame or facilitate fluctuations in the event-occurrences. The critical interaction for the emergence of cascades depends greatly on the network structure in which individuals are connected. We demonstrate that we can predict whether cascades may emerge, given information about the interactions between individuals. Furthermore, we develop a method of reallocating connections among individuals so that event cascades may be either impeded or impelled in a network.

Efficient information transfer by Poisson neurons.

Recently, it has been suggested that certain neurons with Poissonian spiking statistics may communicate by discontinuously switching between two levels of firing intensity. Such a situation resembles in many ways the optimal information transmission protocol for the continuous-time Poisson channel known from information theory. In this contribution we employ the classical information-theoretic results to analyze the efficiency of such a transmission from different perspectives, emphasising the neurobiological viewpoint. We address both the ultimate limits, in terms of the information capacity under metabolic cost constraints, and the achievable bounds on performance at rates below capacity with fixed decoding error probability. In doing so we discuss optimal values of experimentally measurable quantities that can be compared with the actual neuronal recordings in a future effort.

Microscopic instability in recurrent neural networks.

In a manner similar to the molecular chaos that underlies the stable thermodynamics of gases, a neuronal system may exhibit microscopic instability in individual neuronal dynamics while a macroscopic order of the entire population possibly remains stable. In this study, we analyze the microscopic stability of a network of neurons whose macroscopic activity obeys stable dynamics, expressing either monostable, bistable, or periodic state. We reveal that the network exhibits a variety of dynamical states for microscopic instability residing in a given stable macroscopic dynamics. The presence of a variety of dynamical states in such a simple random network implies more abundant microscopic fluctuations in real neural networks which consist of more complex and hierarchically structured interactions.

Analog and digital codes in the brain.

It has long been debated whether information in the brain is coded at the rate of neuronal spiking or at the precise timing of single spikes. Although this issue is essential to the understanding of neural signal processing, it is not easily resolved because the two mechanisms are not mutually exclusive. We suggest revising this coding issue so that one hypothesis is uniquely selected for a given spike train. To this end, we decide whether the spike train is likely to transmit a continuously varying analog signal or switching between active and inactive states. The coding hypothesis is selected by comparing the likelihood estimates yielded by empirical Bayes and hidden Markov models on individual data. The analysis method is applicable to generic event sequences, such as earthquakes, machine noises, and human communications, and enhances the gain in decoding signals and infers underlying activities.

Bursting transition in a linear self-exciting point process.

Self-exciting point processes describe the manner in which every event facilitates the occurrence of succeeding events, as in the case of epidemics or human activity. By increasing excitability, the event occurrences start to exhibit bursts even in the absence of external stimuli. We revealed that the transition is uniquely determined by the average number of events added by a single event, 1-1/√2≈0.2929, independently of the temporal excitation profile. We further extended the theory to multidimensional processes, to be able to incite or inhibit bursting in networks of agents by altering their connections.

Estimating nonstationary inputs from a single spike train based on a neuron model with adaptation.

Because every spike of a neuron is determined by input signals, a train of spikes may contain information about the dynamics of unobserved neurons. A state-space method based on the leaky integrate-and-fire model, describing neuronal transformation from input signals to a spike train has been proposed for tracking input parameters represented by their mean and fluctuation [11]. In the present paper, we propose to make the estimation more realistic by adopting an LIF model augmented with an adaptive moving threshold. Moreover, because the direct state-space method is computationally infeasible for a data set comprising thousands of spikes, we further develop a practical method for transforming instantaneous firing characteristics back to input parameters. The instantaneous firing characteristics, represented by the firing rate and non-Poisson irregularity, can be estimated using a computationally feasible algorithm. We applied our proposed methods to synthetic data to clarify that they perform well.

Estimating inputs and an internal neuronal parameter from a single spike train.

Because neurons are integrating input signals and translating them into timed output spikes, examining spike timing may reveal information about inputs, such as population activities of excitatory and inhibitory presynaptic neurons. Here we construct a state-space method for estimating not only such extrinsic parameters, but also an intrinsic neuronal parameter such as the membrane time constant from a single spike train.

Information transmission using non-poisson regular firing.

In many cortical areas, neural spike trains do not follow a Poisson process. In this study, we investigate a possible benefit of non-Poisson spiking for information transmission by studying the minimal rate fluctuation that can be detected by a Bayesian estimator. The idea is that an inhomogeneous Poisson process may make it difficult for downstream decoders to resolve subtle changes in rate fluctuation, but by using a more regular non-Poisson process, the nervous system can make rate fluctuations easier to detect. We evaluate the degree to which regular firing reduces the rate fluctuation detection threshold. We find that the threshold for detection is reduced in proportion to the coefficient of variation of interspike intervals.

Estimating nonstationary input signals from a single neuronal spike train.

Neurons temporally integrate input signals, translating them into timed output spikes. Because neurons nonperiodically emit spikes, examining spike timing can reveal information about input signals, which are determined by activities in the populations of excitatory and inhibitory presynaptic neurons. Although a number of mathematical methods have been developed to estimate such input parameters as the mean and fluctuation of the input current, these techniques are based on the unrealistic assumption that presynaptic activity is constant over time. Here, we propose tracking temporal variations in input parameters with a two-step analysis method. First, nonstationary firing characteristics comprising the firing rate and non-Poisson irregularity are estimated from a spike train using a computationally feasible state-space algorithm. Then, information about the firing characteristics is converted into likely input parameters over time using a transformation formula, which was constructed by inverting the neuronal forward transformation of the input current to output spikes. By analyzing spike trains recorded in vivo, we found that neuronal input parameters are similar in the primary visual cortex V1 and middle temporal area, whereas parameters in the lateral geniculate nucleus of the thalamus were markedly different.

Detection limit for rate fluctuations in inhomogeneous Poisson processes.

Estimations of an underlying rate from data points are inevitably disturbed by the irregular occurrence of events. Proper estimation methods are designed to avoid overfitting by discounting the irregular occurrence of data, and to determine a constant rate from irregular data derived from a constant probability distribution. However, it can occur that rapid or small fluctuations in the underlying density are undetectable when the data are sparse. For an estimation method, the maximum degree of undetectable rate fluctuations is uniquely determined as a phase transition, when considering an infinitely long series of events drawn from a fluctuating density. In this study, we analytically examine an optimized histogram and a Bayesian rate estimator with respect to their detectability of rate fluctuation, and determine whether their detectable-undetectable phase transition points are given by an identical formula defining a degree of fluctuation in an underlying rate. In addition, we numerically examine the variational Bayes hidden Markov model in its detectability of rate fluctuation, and determine whether the numerically obtained transition point is comparable to those of the other two methods. Such consistency among these three principled methods suggests the presence of a theoretical limit for detecting rate fluctuations.

Neurons as ideal change-point detectors.

Every computational unit in the brain monitors incoming signals, instant by instant, for meaningful changes in the face of stochastic fluctuation. Recent studies have suggested that even a single neuron can detect changes in noisy signals. In this paper, we demonstrate that a single leaky integrate-and-fire neuron can achieve change-point detection close to that of theoretical optimal, for uniform-rate process, functions even better than a Bayes-optimal algorithm when the underlying rate deviates from a presumed uniform rate process. Given a reasonable number of synaptic connections (order 10(4)) and the rate of the input spike train, the values of the membrane time constant and the threshold found for optimizing change-point detection are close to those seen in biological neurons. These findings imply that biological neurons could act as sophisticated change-point detectors.

Elemental spiking neuron model for reproducing diverse firing patterns and predicting precise firing times.

In simulating realistic neuronal circuitry composed of diverse types of neurons, we need an elemental spiking neuron model that is capable of not only quantitatively reproducing spike times of biological neurons given in vivo-like fluctuating inputs, but also qualitatively representing a variety of firing responses to transient current inputs. Simplistic models based on leaky integrate-and-fire mechanisms have demonstrated the ability to adapt to biological neurons. In particular, the multi-timescale adaptive threshold (MAT) model reproduces and predicts precise spike times of regular-spiking, intrinsic-bursting, and fast-spiking neurons, under any fluctuating current; however, this model is incapable of reproducing such specific firing responses as inhibitory rebound spiking and resonate spiking. In this paper, we augment the MAT model by adding a voltage dependency term to the adaptive threshold so that the model can exhibit the full variety of firing responses to various transient current pulses while maintaining the high adaptability inherent in the original MAT model. Furthermore, with this addition, our model is actually able to better predict spike times. Despite the augmentation, the model has only four free parameters and is implementable in an efficient algorithm for large-scale simulation due to its linearity, serving as an element neuron model in the simulation of realistic neuronal circuitry.

Optimizing time histograms for non-Poissonian spike trains.

The time histogram is a fundamental tool for representing the inhomogeneous density of event occurrences such as neuronal firings. The shape of a histogram critically depends on the size of the bins that partition the time axis. In most neurophysiological studies, however, researchers have arbitrarily selected the bin size when analyzing fluctuations in neuronal activity. A rigorous method for selecting the appropriate bin size was recently derived so that the mean integrated squared error between the time histogram and the unknown underlying rate is minimized (Shimazaki & Shinomoto, 2007 ). This derivation assumes that spikes are independently drawn from a given rate. However, in practice, biological neurons express non-Poissonian features in their firing patterns, such that the spike occurrence depends on the preceding spikes, which inevitably deteriorate the optimization. In this letter, we revise the method for selecting the bin size by considering the possible non-Poissonian features. Improvement in the goodness of fit of the time histogram is assessed and confirmed by numerically simulated non-Poissonian spike trains derived from the given fluctuating rate. For some experimental data, the revised algorithm transforms the shape of the time histogram from the Poissonian optimization method.