Simultaneous spike-counts of neural populations are typically modeled by a Gaussian distribution. On short time scales, however, this distribution is too restrictive to describe and analyze multivariate distributions of discrete spike-counts. We present an alternative that is based on copulas and can account for arbitrary marginal distributions, including Poisson and negative binomial distributions as well as second and higher-order interactions. We describe maximum likelihood-based procedures for fitting copula-based models to spike-count data, and we derive a so-called flashlight transformation which makes it possible to move the tail dependence of an arbitrary copula into an arbitrary orthant of the multivariate probability distribution. Mixtures of copulas that combine different dependence structures and thereby model different driving processes simultaneously are also introduced. First, we apply copula-based models to populations of integrate-and-fire neurons receiving partially correlated input and show that the best fitting copulas provide information about the functional connectivity of coupled neurons which can be extracted using the flashlight transformation. We then apply the new method to data which were recorded from macaque prefrontal cortex using a multi-tetrode array. We find that copula-based distributions with negative binomial marginals provide an appropriate stochastic model for the multivariate spike-count distributions rather than the multivariate Poisson latent variables distribution and the often used multivariate normal distribution. The dependence structure of these distributions provides evidence for common inhibitory input to all recorded stimulus encoding neurons. Finally, we show that copula-based models can be successfully used to evaluate neural codes, e.g., to characterize stimulus-dependent spike-count distributions with information measures. This demonstrates that copula-based models are not only a versatile class of models for multivariate distributions of spike-counts, but that those models can be exploited to understand functional dependencies.

Correlations between spike counts are often used to analyze neural coding. The noise is typically assumed to be Gaussian. Yet, this assumption is often inappropriate, especially for low spike counts. In this study, we present copulas as an alternative approach. With copulas it is possible to use arbitrary marginal distributions such as Poisson or negative binomial that are better suited for modeling noise distributions of spike counts. Furthermore, copulas place a wide range of dependence structures at the disposal and can be used to analyze higher order interactions. We develop a framework to analyze spike count data by means of copulas. Methods for parameter inference based on maximum likelihood estimates and for computation of Shannon entropy are provided. We apply the method to our data recorded from macaque prefrontal cortex. The data analysis leads to three significant findings: (1) copula-based distributions provide better fits than discretized multivariate normal distributions; (2) negative binomial margins fit the data better than Poisson margins; and (3) a dependence model that includes only pairwise interactions overestimates the information entropy by at least 19% compared to the model with higher order interactions.