Neurons in many brain areas exhibit high trial-to-trial variability, with spike counts that are overdispersed relative to a Poisson distribution. Recent work (Goris, Movshon, & Simoncelli, 2014 ) has proposed to explain this variability in terms of a multiplicative interaction between a stochastic gain variable and a stimulus-dependent Poisson firing rate, which produces quadratic relationships between spike count mean and variance. Here we examine this quadratic assumption and propose a more flexible family of models that can account for a more diverse set of mean-variance relationships. Our model contains additive gaussian noise that is transformed nonlinearly to produce a Poisson spike rate. Different choices of the nonlinear function can give rise to qualitatively different mean-variance relationships, ranging from sublinear to linear to quadratic. Intriguingly, a rectified squaring nonlinearity produces a linear mean-variance function, corresponding to responses with a constant Fano factor. We describe a computationally efficient method for fitting this model to data and demonstrate that a majority of neurons in a V1 population are better described by a model with a nonquadratic relationship between mean and variance. Finally, we demonstrate a practical use of our model via an application to Bayesian adaptive stimulus selection in closed-loop neurophysiology experiments, which shows that accounting for overdispersion can lead to dramatic improvements in adaptive tuning curve estimation.

A key problem in computational neuroscience is to find simple, tractable models that are nevertheless flexible enough to capture the response properties of real neurons. Here we examine the capabilities of recurrent point process models known as Poisson generalized linear models (GLMs). These models are defined by a set of linear filters and a point nonlinearity and are conditionally Poisson spiking. They have desirable statistical properties for fitting and have been widely used to analyze spike trains from electrophysiological recordings. However, the dynamical repertoire of GLMs has not been systematically compared to that of real neurons. Here we show that GLMs can reproduce a comprehensive suite of canonical neural response behaviors, including tonic and phasic spiking, bursting, spike rate adaptation, type I and type II excitation, and two forms of bistability. GLMs can also capture stimulus-dependent changes in spike timing precision and reliability that mimic those observed in real neurons, and can exhibit varying degrees of stochasticity, from virtually deterministic responses to greater-than-Poisson variability. These results show that Poisson GLMs can exhibit a wide range of dynamic spiking behaviors found in real neurons, making them well suited for qualitative dynamical as well as quantitative statistical studies of single-neuron and population response properties.

One of the central problems in systems neuroscience is to understand how neural spike trains convey sensory information. Decoding methods, which provide an explicit means for reading out the information contained in neural spike responses, offer a powerful set of tools for studying the neural coding problem. Here we develop several decoding methods based on point-process neural encoding models, or forward models that predict spike responses to stimuli. These models have concave log-likelihood functions, which allow efficient maximum-likelihood model fitting and stimulus decoding. We present several applications of the encoding model framework to the problem of decoding stimulus information from population spike responses: (1) a tractable algorithm for computing the maximum a posteriori (MAP) estimate of the stimulus, the most probable stimulus to have generated an observed single- or multiple-neuron spike train response, given some prior distribution over the stimulus; (2) a gaussian approximation to the posterior stimulus distribution that can be used to quantify the fidelity with which various stimulus features are encoded; (3) an efficient method for estimating the mutual information between the stimulus and the spike trains emitted by a neural population; and (4) a framework for the detection of change-point times (the time at which the stimulus undergoes a change in mean or variance) by marginalizing over the posterior stimulus distribution. We provide several examples illustrating the performance of these estimators with simulated and real neural data.

Stimulus reconstruction or decoding methods provide an important tool for understanding how sensory and motor information is represented in neural activity. We discuss Bayesian decoding methods based on an encoding generalized linear model (GLM) that accurately describes how stimuli are transformed into the spike trains of a group of neurons. The form of the GLM likelihood ensures that the posterior distribution over the stimuli that caused an observed set of spike trains is log concave so long as the prior is. This allows the maximum a posteriori (MAP) stimulus estimate to be obtained using efficient optimization algorithms. Unfortunately, the MAP estimate can have a relatively large average error when the posterior is highly nongaussian. Here we compare several Markov chain Monte Carlo (MCMC) algorithms that allow for the calculation of general Bayesian estimators involving posterior expectations (conditional on model parameters). An efficient version of the hybrid Monte Carlo (HMC) algorithm was significantly superior to other MCMC methods for gaussian priors. When the prior distribution has sharp edges and corners, on the other hand, the “hit-and-run” algorithm performed better than other MCMC methods. Using these algorithms, we show that for this latter class of priors, the posterior mean estimate can have a considerably lower average error than MAP, whereas for gaussian priors, the two estimators have roughly equal efficiency. We also address the application of MCMC methods for extracting nonmarginal properties of the posterior distribution. For example, by using MCMC to calculate the mutual information between the stimulus and response, we verify the validity of a computationally efficient Laplace approximation to this quantity for gaussian priors in a wide range of model parameters; this makes direct model-based computation of the mutual information tractable even in the case of large observed neural populations, where methods based on binning the spike train fail. Finally, we consider the effect of uncertainty in the GLM parameters on the posterior estimators.

We examine a cascade encoding model for neural response in which a linear filtering stage is followed by a noisy, leaky, integrate-and-fire spike generation mechanism. This model provides a biophysically more realistic alternative to models based on Poisson (memoryless) spike generation, and can effectively reproduce a variety of spiking behaviors seen in vivo. We describe the maximum likelihood estimator for the model parameters, given only extracellular spike train responses (not intracellular voltage data). Specifically, we prove that the log-likelihood function is concave and thus has an essentially unique global maximum that can be found using gradient ascent techniques. We develop an efficient algorithm for computing the maximum likelihood solution, demonstrate the effectiveness of the resulting estimator with numerical simulations, and discuss a method of testing the model's validity using time-rescaling and density evolution techniques.