A key challenge in functional neuroimaging is the meaningful combination of results across subjects. Even in a sample of healthy participants, brain morphology and functional organization exhibit considerable variability, such that no two individuals have the same neural activation at the same location in response to the same stimulus. This inter-subject variability limits inferences at the group-level as average activation patterns may fail to represent the patterns seen in individuals. A promising approach to multi-subject analysis is group independent component analysis (GICA), which identifies group components and reconstructs activations at the individual level. GICA has gained considerable popularity, particularly in studies where temporal response models cannot be specified. However, a comprehensive understanding of the performance of GICA under realistic conditions of inter-subject variability is lacking. In this study we use simulated functional magnetic resonance imaging (fMRI) data to determine the capabilities and limitations of GICA under conditions of spatial, temporal, and amplitude variability. Simulations, generated with the SimTB toolbox, address questions that commonly arise in GICA studies, such as: (1) How well can individual subject activations be estimated and when will spatial variability preclude estimation? (2) Why does component splitting occur and how is it affected by model order? (3) How should we analyze component features to maximize sensitivity to intersubject differences? Overall, our results indicate an excellent capability of GICA to capture between-subject differences and we make a number of recommendations regarding analytic choices for application to functional imaging data.
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