PT - JOURNAL ARTICLE AU - Adam S. Charles AU - Mijung Park AU - J. Patrick Weller AU - Gregory D. Horwitz AU - Jonathan W. Pillow TI - Dethroning the Fano Factor: a flexible, model-based approach to partitioning neural variability AID - 10.1101/165670 DP - 2017 Jan 01 TA - bioRxiv PG - 165670 4099 - http://biorxiv.org/content/early/2017/07/19/165670.short 4100 - http://biorxiv.org/content/early/2017/07/19/165670.full AB - Neurons in many brain areas exhibit high trial-to-trial variability, with spike counts that are over-dispersed relative to a Poisson distribution. Recent work (Goris et al., 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 sub-linear to linear to multiplicative. Intriguingly, a rectified squaring nonlinearity produces a linear mean-variance function, corresponding to responses with 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 non-quadratic relationship between mean and variance. Lastly, we develop 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.