False discovery rate regression: an application to neural synchrony detection in primary visual cortex

Many approaches for multiple testing begin with the assumption that all tests in a given study should be combined into a global false-discovery-rate analysis. But this may be inappropriate for many of today's large-scale screening problems, where auxiliary information about each test is often available, and where a combined analysis can lead to poorly calibrated error rates within different subsets of the experiment. To address this issue, we introduce an approach called false-discovery-rate regression that directly uses this auxiliary information to inform the outcome of each test. The method can be motivated by a two-groups model in which covariates are allowed to influence the local false discovery rate, or equivalently, the posterior probability that a given observation is a signal. This poses many subtle issues at the interface between inference and computation, and we investigate several variations of the overall approach. Simulation evidence suggests that: (1) when covariate effects are present, FDR regression improves power for a fixed false-discovery rate; and (2) when covariate effects are absent, the method is robust, in the sense that it does not lead to inflated error rates. We apply the method to neural recordings from primary visual cortex. The goal is to detect pairs of neurons that exhibit fine-time-scale interactions, in the sense that they fire together more often than expected due to chance. Our method detects roughly 50% more synchronous pairs versus a standard FDR-controlling analysis. The companion R package FDRreg implements all methods described in the paper

Structure Learning in Coupled Dynamical Systems and Dynamic Causal Modelling

Identifying a coupled dynamical system out of many plausible candidates, each of which could serve as the underlying generator of some observed measurements, is a profoundly ill posed problem that commonly arises when modelling real world phenomena. In this review, we detail a set of statistical procedures for inferring the structure of nonlinear coupled dynamical systems (structure learning), which has proved useful in neuroscience research. A key focus here is the comparison of competing models of (ie, hypotheses about) network architectures and implicit coupling functions in terms of their Bayesian model evidence. These methods are collectively referred to as dynamical casual modelling (DCM). We focus on a relatively new approach that is proving remarkably useful; namely, Bayesian model reduction (BMR), which enables rapid evaluation and comparison of models that differ in their network architecture. We illustrate the usefulness of these techniques through modelling neurovascular coupling (cellular pathways linking neuronal and vascular systems), whose function is an active focus of research in neurobiology and the imaging of coupled neuronal systems

Building population models for large-scale neural recordings: opportunities and pitfalls

Modern recording technologies now enable simultaneous recording from large numbers of neurons. This has driven the development of new statistical models for analyzing and interpreting neural population activity. Here we provide a broad overview of recent developments in this area. We compare and contrast different approaches, highlight strengths and limitations, and discuss biological and mechanistic insights that these methods provide