Fast bootstrapping and permutation testing for assessing reproducibility and interpretability of multivariate fMRI decoding models.

Multivariate decoding models are increasingly being applied to functional magnetic imaging (fMRI) data to interpret the distributed neural activity in the human brain. These models are typically formulated to optimize an objective function that maximizes decoding accuracy. For decoding models trained on full-brain data, this can result in multiple models that yield the same classification accuracy, though some may be more reproducible than others--i.e. small changes to the training set may result in very different voxels being selected. This issue of reproducibility can be partially controlled by regularizing the decoding model. Regularization, along with the cross-validation used to estimate decoding accuracy, typically requires retraining many (often on the order of thousands) of related decoding models. In this paper we describe an approach that uses a combination of bootstrapping and permutation testing to construct both a measure of cross-validated prediction accuracy and model reproducibility of the learned brain maps. This requires re-training our classification method on many re-sampled versions of the fMRI data. Given the size of fMRI datasets, this is normally a time-consuming process. Our approach leverages an algorithm called fast simultaneous training of generalized linear models (FaSTGLZ) to create a family of classifiers in the space of accuracy vs. reproducibility. The convex hull of this family of classifiers can be used to identify a subset of Pareto optimal classifiers, with a single-optimal classifier selectable based on the relative cost of accuracy vs. reproducibility. We demonstrate our approach using full-brain analysis of elastic-net classifiers trained to discriminate stimulus type in an auditory and visual oddball event-related fMRI design. Our approach and results argue for a computational approach to fMRI decoding models in which the value of the interpretation of the decoding model ultimately depends upon optimizing a joint space of accuracy and reproducibility.