Statistical similarities between neuronal spike trains could reveal significant information on complex underlying processing. In general, the similarity between synchronous spike trains is somewhat easy to identify. However, the similar patterns also potentially appear in an asynchronous manner. However, existing methods for their identification tend to converge slowly, and cannot be applied to short sequences. In response, we propose Hellinger distance measure based on empirical probabilities, which we show to be as accurate as existing techniques, yet faster to converge for synthetic as well as experimental spike trains. Further, we cluster pairs of neuronal spike trains based on statistical similarities and found two non-overlapping classes, which could indicate functional similarities in neurons. Significantly, our technique detected functional heterogeneity in pairs of neuronal responses with the same performance as existing techniques, while exhibiting faster convergence. We expect the proposed method to facilitate large-scale studies of functional clustering, especially involving short sequences, which would in turn identify signatures of various diseases in terms of clustering patterns.
Quantification of neuronal correlations in neuron populations helps us to understand neural coding rules. Such quantification could also reveal how neurons encode information in normal and disease conditions like Alzheimer's and Parkinson's. While neurons communicate with each other by transmitting spikes, there would be a change in calcium concentration within the neurons inherently. Accordingly, there would be correlations in calcium spike trains and they could have heterogeneous memory structures. In this context, estimation of mutual information rate in calcium spike trains assumes primary…
With the increasing popularity of calcium imaging data in neuroscience research, methods for analyzing calcium trace data are critical to address various questions. The observed calcium traces are either analyzed directly or deconvolved to spike trains to infer neuronal activities. When both approaches are applicable, it is unclear whether deconvolving calcium traces is a necessary step. In this article, we compare the performance of using calcium traces or their deconvolved spike trains for three common analyses: clustering, principal component analysis (PCA), and population decoding. Our sim…
NMDA receptors (NMDA-R) typically contribute to excitatory synaptic transmission in the central nervous system. While calcium influx through NMDA-R plays a critical role in synaptic plasticity, experimental evidence indicates that NMDAR-mediated calcium influx also modifies neuronal excitability through the activation of calcium-activated potassium channels. This mechanism has not yet been studied theoretically. Our theoretical model provides a simple description of neuronal electrical activity that takes into account the tonic activity of extrasynaptic NMDA receptors and a cytosolic calcium c…
Understanding the role of astrocytes in brain computation is a nascent challenge, promising immense rewards, in terms of new neurobiological knowledge that can be translated into artificial intelligence. In our ongoing effort to identify principles endow-ing the astrocyte with unique functions in brain computation, and translate them into neural-astrocytic networks (NANs), we propose a biophysically realistic model of an astrocyte that preserves the experimentally observed spatial allocation of its distinct subcellular compartments. We show how our model may encode, and modu-late, the extent o…
Calcium imaging has become a powerful and popular technique to monitor the activity of large populations of neurons in vivo. However, for ethical considerations and despite recent technical developments, recordings are still constrained to a limited number of trials and animals. This limits the amount of data available from individual experiments and hinders the development of analysis techniques and models for more realistic sizes of neuronal populations. The ability to artificially synthesize realistic neuronal calcium signals could greatly alleviate this problem by scaling up the number of …
Neuronal assemblies, loosely defined as subsets of neurons with reoccurring spatio-temporally coordinated activation patterns, or "motifs", are thought to be building blocks of neural representations and information processing. We here propose LeMoNADe, a new exploratory data analysis method that facilitates hunting for motifs in calcium imaging videos, the dominant microscopic functional imaging modality in neurophysiology. Our nonparametric method extracts motifs directly from videos, bypassing the difficult intermediate step of spike extraction. Our technique augments variational autoencode…
Connected networks are a fundamental structure of neurobiology. Understanding these networks will help us elucidate the neural mechanisms of computation. Mathematically speaking these networks are `graphs' - structures containing objects that are connected. In neuroscience, the objects could be regions of the brain, e.g. fMRI data, or be individual neurons, e.g. calcium imaging with fluorescence microscopy. The formal study of graphs, graph theory, can provide neuroscientists with a large bank of algorithms for exploring networks. Graph theory has already been applied in a variety of ways to f…
Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies sinc…
We present efficient Bayesian methods for extracting neuronal spiking information from calcium imaging data. The goal of our methods is to sample from the posterior distribution of spike trains and model parameters (baseline concentration, spike amplitude etc) given noisy calcium imaging data. We present discrete time algorithms where we sample the existence of a spike at each time bin using Gibbs methods, as well as continuous time algorithms where we sample over the number of spikes and their locations at an arbitrary resolution using Metropolis-Hastings methods for point processes. We provi…
Application of an attention-based CNN-BiLSTM framework for in vivo two-photon calcium imaging of neuronal ensembles: decoding complex bilateral forelimb movements from unilateral M1
West Virginia University（西弗吉尼亚大学）；University of Miami（迈阿密大学）；Leonard M. Miller School of Medicine（伦纳德·M·米勒医学院）；Rockefeller Neuroscience Institute（洛克菲勒神经科学研究所）
One step in the conventional analysis of extracellularly recorded neuronal data is spike sorting, which separates electrical signal into action potentials from different neurons. Because spike sorting involves human judgment, it can be subjective and time intensive, particularly for large sets of neurons. Here we propose a simple, automated way to construct alternative representations of neuronal activity, called spectral representation (SR). In this approach, neuronal spikes are mapped to a discrete space of spike- waveform features and time. Spectral representation enables us to find single-…
Neuronal dynamics are fundamentally constrained by the underlying structural network architecture, yet much of the details of this synaptic connectivity are still unknown even in neuronal cultures in vitro. Here we extend a previous approach based on information theory, the Generalized Transfer Entropy, to the reconstruction of connectivity of simulated neuronal networks of both excitatory and inhibitory neurons. We show that, due to the model-free nature of the developed measure, both kinds of connections can be reliably inferred if the average firing rate between synchronous burst events exc…
A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically unfeasible even in dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct approximations to network structural connectivities from network activity monitored through calcium fluorescence imaging. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time-series of ca…
We investigate the stimulus-dependent tuning properties of a noisy ionic conductance model for intrinsic subthreshold oscillations in membrane potential and associated spike generation. On depolarization by an applied current, the model exhibits subthreshold oscillatory activity with occasional spike generation when oscillations reach the spike threshold. We consider how the amount of applied current, the noise intensity, variation of maximum conductance values and scaling to different temperature ranges alter the responses of the model with respect to voltage traces, interspike intervals and …
A common way of studying the relationship between neural activity and behavior is through the analysis of neuronal spike trains that are recorded using one or more electrodes implanted in the brain. Each spike train typically contains spikes generated by multiple neurons. A natural question that arises is "what is the number of neurons $ν$ generating the spike train?"; This article proposes a method-of-moments technique for estimating $ν$. This technique estimates the noise nonparametrically using data from the silent region of the spike train and it applies to isolated spikes with a possibly …
Chimera states are spatiotemporal patterns in which coherence and incoherence coexist. We observe the coexistence of synchronous (coherent) and desynchronous (incoherent) domains in a neuronal network. The network is composed of coupled adaptive exponential integrate-and-fire neurons that are connected by means of chemical synapses. In our neuronal network, the chimera states exhibit spatial structures both with spikes and bursts activities. Furthermore, those desynchronised domains not only have either spike or burst activity, but we show that the structures switch between spikes and bursts a…
Calcium imaging for observing spiking activity from large populations of neurons are quickly gaining popularity. While the raw data are fluorescence movies, the underlying spike trains are of interest. This work presents a fast non-negative deconvolution filter to infer the approximately most likely spike train for each neuron, given the fluorescence observations. This algorithm outperforms optimal linear deconvolution (Wiener filtering) on both simulated and biological data. The performance gains come from restricting the inferred spike trains to be positive (using an interior-point method), …
A good understanding of how neurons use electrical pulses (i.e, spikes) to encode the signal information remains elusive. Analyzing spike sequences generated by individual neurons and by two coupled neurons (using the stochastic FitzHugh-Nagumo model), recent theoretical studies have found that the relative timing of the spikes can encode the signal information. Using a symbolic method to analyze the spike sequence, preferred and infrequent spike patterns were detected, whose probabilities vary with both, the amplitude and the frequency of the signal. To investigate if this encoding mechanism …
Two-photon imaging of calcium indicators allows simultaneous recording of responses of hundreds of neurons over hours and even days, but provides a relatively indirect measure of their spiking activity. Existing deconvolution algorithms attempt to recover spikes from observed imaging data, which are then commonly subjected to the same analyses that are applied to electrophysiologically recorded spikes (e.g., estimation of average firing rates, or tuning curves). Here we show, however, that in the presence of noise this approach is often heavily biased. We propose an alternative analysis that a…
Persistent activity is postulated to drive neural network plasticity and learning. To investigate its underlying cellular mechanisms, we developed a biophysically tractable model that explains the emergence, sustenance, and eventual termination of short-term persistent activity. Using the model, we reproduced the features of reverberating activity that were observed in small (50-100 cells) networks of cultured hippocampal neurons, such as the appearance of polysynaptic current clusters, the typical inter-cluster intervals, the typical duration of reverberation, and the response to changes in e…
We derive exact analytical expressions for the cumulants of any orders of neuronal membrane potentials driven by spike trains in a multivariate Hawkes process model with excitation and inhibition. Such expressions can be used for the prediction and sensitivity analysis of the statistical behavior of the model over time, and to estimate the probability densities of neuronal membrane potentials using Gram-Charlier expansions. Our results are shown to provide a better alternative to Monte Carlo estimates via stochastic simulations, and computer codes based on combinatorial recursions are included…
Integration of Calcium Imaging Traces via Deep Generative Modeling
Dept. of Biomedical Sciences \& Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain Dept. of Condensed Matter Physics, Universitat de Barcelona, Barcelona, Spain
Reduced models of neuronal activity such as Integrate-and-Fire models allow a description of neuronal dynamics in simple, intuitive terms and are easy to simulate numerically. We present a method to fit an Integrate-and-Fire-type model of neuronal activity, namely a modified version of the Spike Response Model, to a detailed Hodgkin-Huxley-type neuron model driven by stochastic spike arrival. In the Hogkin-Huxley model, spike arrival at the synapse is modeled by a change of synaptic conductance. For such conductance spike input, more than 70% of the postsynaptic action potentials can be predic…
We investigated the influence of efficacy of synaptic interaction on firing synchronization in excitatory neuronal networks. We found spike death phenomena, namely, the state of neurons transits from limit cycle to fixed point or transient state. The phenomena occur under the perturbation of excitatory synaptic interaction that has a high efficacy. We showed that the decrease of synaptic current results in spike death through depressing the feedback of sodium ionic current. In the networks with spike death property the degree of synchronization is lower and unsensitive to the heterogeneity of …
Discovering the 'Neural Code' from multi-neuronal spike trains is an important task in neuroscience. For such an analysis, it is important to unearth interesting regularities in the spiking patterns. In this report, we present an efficient method for automatically discovering synchrony, synfire chains, and more general sequences of neuronal firings. We use the Frequent Episode Discovery framework of Laxman, Sastry, and Unnikrishnan (2005), in which the episodes are represented and recognized using finite-state automata. Many aspects of functional connectivity between neuronal populations can b…
Our mysterious brain is believed to operate near a non-equilibrium point and generate critical self-organized avalanches in neuronal activity. Recent experimental evidence has revealed significant heterogeneity in both synaptic input and output connectivity, but whether the structural heterogeneity participates in the regulation of neuronal avalanches remains poorly understood. By computational modelling, we predict that different types of structural heterogeneity contribute distinct effects on avalanche neurodynamics. In particular, neuronal avalanches can be triggered at an intermediate leve…
The synaptic connectivity of cortex is plastic, with experience shaping the ongoing interactions between neurons. Theoretical studies of spike timing-dependent plasticity (STDP) have focused on either just pairs of neurons or large-scale simulations where analytic insight is lacking. A simple account for how fast spike time correlations affect both micro- and macroscopic network structure remains lacking. We develop a low-dimensional mean field theory showing how STDP gives rise to strongly coupled assemblies of neurons with shared stimulus preferences, with the connectivity actively reinforce…
Recent studies of cortical neurons driven by fluctuating currents revealed cutoff frequencies for action potential encoding of several hundred Hz. Theoretical studies of biophysical neuron models have predicted a much lower cutoff frequency of the order of average firing rate or the inverse membrane time constant. The biophysical origin of the observed high cutoff frequencies is thus not well understood. Here we introduce a neuron model with dynamical action potential generation, in which the linear response can be analytically calculated for uncorrelated synaptic noise. We find that the cutof…
In this paper, we study the effects of spike timing-dependent plasticity on synchronisation in a network of Hodgkin-Huxley neurons. Neuron plasticity is a flexible property of a neuron and its network to change temporarily or permanently their biochemical, physiological, and morphological characteristics, in order to adapt to the environment. Regarding the plasticity, we consider Hebbian rules, specifically for spike timing-dependent plasticity (STDP), and with regard to network, we consider that the connections are randomly distributed. We analyse the synchronisation and desynchronisation acc…
Neuroprosthesis, as one type of precision medicine device, is aiming for manipulating neuronal signals of the brain in a closed-loop fashion, together with receiving stimulus from the environment and controlling some part of our brain/body. In terms of vision, incoming information can be processed by the brain in millisecond interval. The retina computes visual scenes and then sends its output as neuronal spikes to the cortex for further computation. Therefore, the neuronal signal of interest for retinal neuroprosthesis is spike. Closed-loop computation in neuroprosthesis includes two stages: …
School of Electrical Engineering and Computer Science（电气工程与计算机科学学院）；The Pennsylvania State University（宾夕法尼亚州立大学）
Developing electrophysiological recordings of brain neuronal activity and their analysis provide a basis for exploring the structure of brain function and nervous system investigation. The recorded signals are typically a combination of spikes and noise. High amounts of background noise and possibility of electric signaling recording from several neurons adjacent to the recording site have led scientists to develop neuronal signal processing tools such as spike sorting to facilitate brain data analysis. Spike sorting plays a pivotal role in understanding the electrophysiological activity of ne…
The recent development of genetically encoded calcium indicators enables monitoring in vivo the activity of neuronal populations. Most analysis of these calcium transients relies on linear regression analysis based on the sensory stimulus applied or the behavior observed. To estimate the basic properties of the functional neural circuitry, we propose a network-based approach based on calcium imaging recorded at single cell resolution. Differently from previous analysis based on cross-correlation, we used Granger-causality estimates to infer activity propagation between the activities of differ…
Deducing the structure of neural circuits is one of the central problems of modern neuroscience. Recently-introduced calcium fluorescent imaging methods permit experimentalists to observe network activity in large populations of neurons, but these techniques provide only indirect observations of neural spike trains, with limited time resolution and signal quality. In this work we present a Bayesian approach for inferring neural circuitry given this type of imaging data. We model the network activity in terms of a collection of coupled hidden Markov chains, with each chain corresponding to a si…
We present a modified library-based method for simulating the Hodgkin-Huxley (HH) neuronal networks. By pre-computing a high resolution data library during the interval of an action potential (spike), we can avoid evolving the HH equations during the spike and can use a large time step to raise efficiency. The library method can stably achieve at most 10 times of speedup compared with the regular Runge-Kutta method while capturing most statistical properties of HH neurons like the distribution of spikes which data is widely used in the statistical analysis like transfer entropy and Granger cau…
We establish a general linear response relation for spiking neuronal networks, based on chains with unbounded memory. This relation allows us to predict the influence of a weak amplitude time-dependent external stimuli on spatio-temporal spike correlations, from the spontaneous statistics (without stimulus) in a general context where the memory in spike dynamics can extend arbitrarily far in the past. Using this approach, we show how linear response is explicitly related to neuronal dynamics with an example, the gIF model, introduced by M. Rudolph and A. Destexhe. This example illustrates the …
Calcium imaging data promises to transform the field of neuroscience by making it possible to record from large populations of neurons simultaneously. However, determining the exact moment in time at which a neuron spikes, from a calcium imaging data set, amounts to a non-trivial deconvolution problem which is of critical importance for downstream analyses. While a number of formulations have been proposed for this task in the recent literature, in this paper we focus on a formulation recently proposed in Jewell and Witten (2017) which has shown initial promising results. However, this proposa…
An essential step toward understanding neural circuits is linking their structure and their dynamics. In general, this relationship can be almost arbitrarily complex. Recent theoretical work has, however, begun to identify some broad principles underlying collective spiking activity in neural circuits. The first is that local features of network connectivity can be surprisingly effective in predicting global statistics of activity across a network. The second is that, for the important case of large networks with excitatory-inhibitory balance, correlated spiking persists or vanishes depending …
Branching with immigration is one of the most common models for the stochastic processes observed in neuronal circuits. However, it is not observed directly and, in order to create branching-like processes, the observed spike time series is processed by attaching time bins to spikes. It has been shown that results such as criticality and size distributions depend on the chosen time bin. A different methodology whose results do not depend on the choice of time bin might therefore be useful and is proposed in this article. The new methodology circumvents using time bins altogether by replacing t…
Interval jitter and spike resampling methods are used to analyze the time scale on which temporal correlations occur. They allow the computation of jitter corrected cross correlograms and the performance of an associated statistically robust hypothesis test to decide whether observed correlations at a given time scale are significant. Currently used Monte Carlo methods approximate the probability distribution of coincidences. They require generating $N_{\rm MC}$ simulated spike trains of length $T$ and calculating their correlation with another spike train up to lag $τ_{\max}$. This is computa…
Many types of neurons exhibit spike rate adaptation, mediated by intrinsic slow $\mathrm{K}^+$-currents, which effectively inhibit neuronal responses. How these adaptation currents change the relationship between in-vivo like fluctuating synaptic input, spike rate output and the spike train statistics, however, is not well understood. In this computational study we show that an adaptation current which primarily depends on the subthreshold membrane voltage changes the neuronal input-output relationship (I-O curve) subtractively, thereby increasing the response threshold. A spike-dependent adap…
Discovering frequent episodes in event sequences is an interesting data mining task. In this paper, we argue that this framework is very effective for analyzing multi-neuronal spike train data. Analyzing spike train data is an important problem in neuroscience though there are no data mining approaches reported for this. Motivated by this application, we introduce different temporal constraints on the occurrences of episodes. We present algorithms for discovering frequent episodes under temporal constraints. Through simulations, we show that our method is very effective for analyzing spike tra…
Calcium imaging is an essential tool to study the activity of neuronal populations. However, the high level of background fluorescence in images hinders the accurate identification of neurons and the extraction of neuronal activities. While robust principal component analysis (RPCA) is a promising method that can decompose the foreground and background in such images, its computational complexity and memory requirement are prohibitively high to process large-scale calcium imaging data. Here, we propose BEAR, a simple bilinear neural network for the efficient approximation of RPCA which achieve…
Biocomputing technologies exploit biological communication mechanisms involving cell-cell signal propagation to perform computations. Researchers recently worked toward realising logic gates made by neurons to develop novel devices such as organic neuroprostheses or brain implants made by cells, herein termed living implants. Several challenges arise from this approach, mainly associated with the stochastic nature and noise of neuronal communication. Since astrocytes play a crucial role in the regulation of neurons activity, there is a possibility whereby astrocytes can be engineered to contro…
Understanding the functioning of a neural system in terms of its underlying circuitry is an important problem in neuroscience. Recent developments in electrophysiology and imaging allow one to simultaneously record activities of hundreds of neurons. Inferring the underlying neuronal connectivity patterns from such multi-neuronal spike train data streams is a challenging statistical and computational problem. This task involves finding significant temporal patterns from vast amounts of symbolic time series data. In this paper we show that the frequent episode mining methods from the field of te…
Extracellular recordings with multi-electrode arrays is one of the basic tools of contemporary neuroscience. These recordings are mostly used to monitor the activities, understood as sequences of emitted action potentials, of many individual neurons. But the raw data produced by extracellular recordings are most commonly a mixture of activities from several neurons. In order to get the activities of the individual contributing neurons, a pre-processing step called spike sorting is required. We present here a pure Python implementation of a well tested spike sorting procedure. The latter was de…
Neural coding is a field of study that concerns how sensory information is represented in the brain by networks of neurons. The link between external stimulus and neural response can be studied from two parallel points of view. The first, neural encoding refers to the mapping from stimulus to response, and primarily focuses on understanding how neurons respond to a wide variety of stimuli, and on constructing models that accurately describe the stimulus-response relationship. Neural decoding, on the other hand, refers to the reverse mapping, from response to stimulus, where the challenge is to…
We consider here a single-compartment model of these neurons which is capable of describing many of the known features of spike generation, particularly the slow rhythmic pacemaking activity often observed in these cells in a variety of species. Included in the model are ten kinds of voltage dependent ion channels as well as calcium-dependent potassium current. Calcium dynamics includes buffering and pumping. In sections 3-9, each component is considered in detail and parameters estimated from voltage clamp data where possible. In the next two sections simplified versions of some components ar…
Background: Spike trains of multiple neurons can be analyzed following the summed population (SP) or the labeled line (LL) hypothesis. Responses to external stimuli are generated by a neuronal population as a whole or the individual neurons have encoding capacities of their own. The SPIKE-distance estimated either for a single, pooled spike train over a population or for each neuron separately can serve to quantify these responses. New Method: For the SP case we compare three algorithms that search for the most discriminative subpopulation over all stimulus pairs. For the LL case we introduce …
Biological systems are notoriously noisy. Noise, therefore, also plays an important role in many models of neural impulse generation. Noise is not only introduced for more realistic simulations but also to account for cooperative effects between noisy and nonlinear dynamics. Often, this is achieved by a simple noise term in the membrane equation (current noise). However, there are ongoing discussions whether such current noise is justified or whether rather conductance noise should be introduced because it is closer to the natural origin of noise. Therefore, we have compared the effects of cur…
The threshold voltage for action potential generation is a key regulator of neuronal signal transduction, yet the mechanism of its dynamic variation is still not well described. In this paper, we propose that threshold phenomena can be classified as parameter thresholds and state thresholds. Voltage thresholds which belong to the state threshold are determined by the `general separatrix' in state space. We demonstrate that the separatrix generally exists in the state space of neuron models. The general form of separatrix was assumed as the function of both states and stimuli and the previously…
We show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks. In contrast, if the probability of interneuronal c…
One of the main current issues in Neurobiology concerns the understanding of interrelated spiking activity among multineuronal ensembles and differences between stimulus-driven and spontaneous activity in neurophysiological experiments. Multi electrode array recordings that are now commonly used monitor neuronal activity in the form of spike trains from many well identified neurons. A basic question when analyzing such data is the identification of the directed graph describing "synaptic coupling" between neurons. In this article we deal with this matter working with a high quality multielectr…
