Evaluating Approaches for Inference Testing of Whole-Brain Densely Sampled Single-Subject Task fMRI Data

Task-based precision mapping has become a promising technique in functional MRI (fMRI) to robustly characterize and map an individual's unique activity patterns. These experiments consist of acquiring extensive imaging data in one participant, ultimately improving the sensitivity and specificity of individual-specific functional localization. Despite its advantages, studies have primarily focused on understanding individual-specific cortical activation, preventing a holistic view of a systems-level functional response, and to date, best approaches for the statistical analysis of controlled task-based, densely sampled, whole-brain data have not yet been fully established. Therefore, in this study, we collected whole-brain (i.e. covering cortex, cerebellum, and brainstem) multi-echo densely sampled data of the auditory system, a system with major subcortical components, and evaluated activation sensitivity as well as activation stability across data subsets of commonly-used whole-brain and region-specific inference testing approaches. The whole-brain approaches involved standard voxel-level and cluster-level inference schemes with varying statistical thresholds and a non-parametric permutation inference approach. The region-specific approaches involved an exploratory top % t-statistics methods and non-parametric permutation inference approaches. We found that a whole-brain voxel-level approach with a false discovery rate (FDR) correction (p<0.05) presented highest sensitivity across regions and subjects as well as most consistent detection of expected auditory regions, even with lower scan duration. In addition, we found that a region-specific top % t-statistic approach may be a useful exploratory functional localization tool and a complementary method to standard inference testing approaches.