Quantitative evaluation of statistical inference in resting state functional MRI.

Modern statistical inference techniques may be able to improve the sensitivity and specificity of resting state functional MRI (rs-fMRI) connectivity analysis through more realistic characterization of distributional assumptions. In simulation, the advantages of such modern methods are readily demonstrable. However quantitative empirical validation remains elusive in vivo as the true connectivity patterns are unknown and noise/artifact distributions are challenging to characterize with high fidelity. Recent innovations in capturing finite sample behavior of asymptotically consistent estimators (i.e., SIMulation and EXtrapolation - SIMEX) have enabled direct estimation of bias given single datasets. Herein, we leverage the theoretical core of SIMEX to study the properties of inference methods in the face of diminishing data (in contrast to increasing noise). The stability of inference methods with respect to synthetic loss of empirical data (defined as resilience) is used to quantify the empirical performance of one inference method relative to another. We illustrate this new approach in a comparison of ordinary and robust inference methods with rs-fMRI.