Estimating a Separably Markov Random Field from Binary Observations

A fundamental problem in neuroscience is to characterize the dynamics of spiking from the neurons in a circuit that is involved in learning about a stimulus or a contingency. A key limitation of current methods to analyze neural spiking data is the need to collapse neural activity over time or trials, which may cause the loss of information pertinent to understanding the function of a neuron or circuit. We introduce a new method that can determine not only the trial-to-trial dynamics that accompany the learning of a contingency by a neuron, but also the latency of this learning with respect to the onset of a conditioned stimulus. The backbone of the method is a separable two-dimensional (2D) random field (RF) model of neural spike rasters, in which the joint conditional intensity function of a neuron over time and trials depends on two latent Markovian state sequences that evolve separately but in parallel. Classical tools to estimate state-space models cannot be applied readily to our 2D separable RF model. We develop efficient statistical and computational tools to estimate the parameters of the separable 2D RF model. We apply these to data collected from neurons in the prefrontal cortex in an experiment designed to characterize the neural underpinnings of the associative learning of fear in mice. Overall, the separable 2D RF model provides a detailed, interpretable characterization of the dynamics of neural spiking that accompany the learning of a contingency.

Stochastic Models for the Infectivity Function in an Infinite Population of Susceptible Individuals

Two stochastic models to study the course of the transient behaviour of the total infectivity present in an infinite population of susceptible individuals are developed. The conditional intensity function of the contagion comprises two components: one is due to the external sources only and the other is the contribution of each of the infected persons which is nonstationary in nature. The statistical characteristics of the number of infected individuals at any time are explicitly obtained. Estimation of the model parameters is also indicated.

Likelihood Methods for Point Processes with Refractoriness

Likelihood-based encoding models founded on point processes have received significant attention in the literature because of their ability to reveal the information encoded by spiking neural populations. We propose an approximation to the likelihood of a point-process model of neurons that holds under assumptions about the continuous time process that are physiologically reasonable for neural spike trains: the presence of a refractory period, the predictability of the conditional intensity function, and its integrability. These are properties that apply to a large class of point processes arising in applications other than neuroscience. The proposed approach has several advantages over conventional ones. In particular, one can use standard fitting procedures for generalized linear models based on iteratively reweighted least squares while improving the accuracy of the approximation to the likelihood and reducing bias in the estimation of the parameters of the underlying continuous-time model. As a result, the proposed approach can use a larger bin size to achieve the same accuracy as conventional approaches would with a smaller bin size. This is particularly important when analyzing neural data with high mean and instantaneous firing rates. We demonstrate these claims on simulated and real neural spiking activity. By allowing a substantive increase in the required bin size, our algorithm has the potential to lower the barrier to the use of point-process methods in an increasing number of applications.

A Computationally Efficient Method for Nonparametric Modeling of Neural Spiking Activity with Point Processes

Point-process models have been shown to be useful in characterizing neural spiking activity as a function of extrinsic and intrinsic factors. Most point-process models of neural activity are parametric, as they are often efficiently computable. However, if the actual point process does not lie in the assumed parametric class of functions, misleading inferences can arise. Nonparametric methods are attractive due to fewer assumptions, but computation in general grows with the size of the data. We propose a computationally efficient method for nonparametric maximum likelihood estimation when the conditional intensity function, which characterizes the point process in its entirety, is assumed to be a Lipschitz continuous function but otherwise arbitrary. We show that by exploiting much structure, the problem becomes efficiently solvable. We next demonstrate a model selection procedure to estimate the Lipshitz parameter from data, akin to the minimum description length principle and demonstrate consistency of our estimator under appropriate assumptions. Finally, we illustrate the effectiveness of our method with simulated neural spiking data, goldfish retinal ganglion neural data, and activity recorded in CA1 hippocampal neurons from an awake behaving rat. For the simulated data set, our method uncovers a more compact representation of the conditional intensity function when it exists. For the goldfish and rat neural data sets, we show that our nonparametric method gives a superior absolute goodness-of-fit measure used for point processes than the most common parametric and splines-based approaches.

Kernel estimation and display of a five-dimensional conditional intensity function

The aim of this paper is to find a convenient and effective method of displaying some second order properties in a neighbourhood of a selected point of the process. The used techniques are based on very general high-dimensional nonparametric smoothing developed to define a more general version of the conditional intensity function introduced in earlier earthquake studies by Vere-Jones (1978).

Valuations for Spike Train Prediction

The ultimate product of an electrophysiology experiment is often a decision on which biological hypothesis or model best explains the observed data. We outline a paradigm designed for comparison of different models, which we refer to as spike train prediction. A key ingredient of this paradigm is a prediction quality valuation that estimates how close a predicted conditional intensity function is to an actual observed spike train. Although a valuation based on log likelihood (L) is most natural, it has various complications in this context. We propose that a quadratic valuation (Q) can be used as an alternative to L. Q shares some important theoretical properties with L, including consistency, and the two valuations perform similarly on simulated and experimental data. Moreover, Q is more robust than L, and optimization with Q can dramatically improve computational efficiency. We illustrate the utility of Q for comparing models of peer prediction, where it can be computed directly from cross-correlograms. Although Q does not have a straightforward probabilistic interpretation, Q is essentially given by Euclidean distance.

A Point Process Framework for Relating Neural Spiking Activity to Spiking History, Neural Ensemble, and Extrinsic Covariate Effects

Multiple factors simultaneously affect the spiking activity of individual neurons. Determining the effects and relative importance of these factors is a challenging problem in neurophysiology. We propose a statistical framework based on the point process likelihood function to relate a neuron's spiking probability to three typical covariates: the neuron's own spiking history, concurrent ensemble activity, and extrinsic covariates such as stimuli or behavior. The framework uses parametric models of the conditional intensity function to define a neuron's spiking probability in terms of the covariates. The discrete time likelihood function for point processes is used to carry out model fitting and model analysis. We show that, by modeling the logarithm of the conditional intensity function as a linear combination of functions of the covariates, the discrete time point process likelihood function is readily analyzed in the generalized linear model (GLM) framework. We illustrate our approach for both GLM and non-GLM likelihood functions using simulated data and multivariate single-unit activity data simultaneously recorded from the motor cortex of a monkey performing a visuomotor pursuit-tracking task. The point process framework provides a flexible, computationally efficient approach for maximum likelihood estimation, goodness-of-fit assessment, residual analysis, model selection, and neural decoding. The framework thus allows for the formulation and analysis of point process models of neural spiking activity that readily capture the simultaneous effects of multiple covariates and enables the assessment of their relative importance.