Huanjie Li, Lisa D. Nickerson, Jinhu Xiong, Qihong Zou, Yang Fan, Yajun Ma, Tingqi Shi, Jianqiao Ge, Jia-Hong Gao

Cluster-size tests (CST) based on random field theory have been widely adopted in fMRI data analysis to detect brain activation. However, most existing approaches can be used appropriately only when the image is highly smoothed in the spatial domain. Unfortunately, spatial smoothing degrades spatial specificity. Recently, a threshold-free cluster enhancement technique was proposed which does not require spatial smoothing, but this method can be used only for group level analysis. Advances in imaging technology now yield high quality high spatial resolution imaging data in single subjects and an inference approach that retains the benefits of greater spatial resolution is called for. In this work, we present a new CST with a correction for voxelation to address this problem. The theoretical formulation of the new approach based on Gaussian random fields is developed to estimate statistical significance using 3D statistical parametric maps without assuming spatial smoothness. Simulated phantom and resting-state fMRI experimental data are then used to compare the voxelation-corrected procedure to the widely used standard random field theory. Unlike standard random field theory approaches, which require heavy spatial smoothing, the new approach has a higher sensitivity for localizing activation regions without the requirement of spatial smoothness.