title: Adjusting the neuroimaging statistical inferences for nonstationarity.
abstract: In neuroimaging cluster-based inference has generally been found to be more powerful than voxel-wise inference. However standard cluster-based methods assume stationarity (constant smoothness), while under nonstationarity clusters are larger in smooth regions just by chance, making false positive risk spatially variant. Hayasaka et al. proposed a Random Field Theory (RFT) based nonstationarity adjustment for cluster inference and validated the method in terms of controlling the overall family-wise false positive rate. The RFT-based methods, however, have never been directly assessed in terms of homogeneity of local false positive risk. In this work we propose a new cluster size adjustment that accounts for local smoothness, based on local empirical cluster size distributions and a two-pass permutation method. We also propose a new approach to measure homogeneity of local false positive risk, and use this method to compare the RFT-based and our new empirical adjustment methods. We apply these techniques to both cluster-based and a related inference, threshold-free cluster enhancement (TFCE). Using simulated and real data we confirm the expected heterogeneity in false positive risk with unadjusted cluster inference but find that RFT-based adjustment does not fully eliminate heterogeneity; we also observe that our proposed empirical adjustment dramatically increases the homogeneity and TFCE inference is generally quite robust to nonstationarity.
authors.affiliation: Centre for Functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK. reza@fmrib.ox.ac.uk
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Salimi-Khorshidi
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nichols
mesh_terms: D000465:Algorithms; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008959:Models, Neurological; D015233:Models, Statistical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013269:Stochastic Processes