Regression models for partially localized fMRI connectivity analyses

Brain functional connectivity analysis of resting-state functional magnetic resonance imaging (fMRI) data is typically performed in a standardized template space assuming consistency of connections across subjects. This can come in the form of one-edge-at-a-time analyses or dimension reduction/decomposition methods. Common to these approaches is the assumption of complete localization (or spatial alignment) of brain regions across subjects. Alternative approaches completely eschew localization assumptions by treating connections as statistically exchangeable (for example, using the density of connectivity between nodes). Yet other approaches, such as hyperalignment, attempt to align subjects on function as well as structure, thereby achieving a different sort of template-based localization. In this paper, we propose the use of simple regression models to characterize connectivity. To that end, we build regression models on subject-level Fisher transformed regional connection matrices using geographic distance, homotopic distance, network labels, and region indicators as covariates to explain variation in connections. While we perform our analysis in template-space in this paper, we envision the method being useful in multi-atlas registration settings, where subject data remains in its own geometry and templates are warped instead. A byproduct of this style of analysis is the ability to characterize the fraction of variation in subject-level connections explained by each type of covariate. Using Human Connectome Project data, we found that network labels and regional characteristics contribute far more than geographic or homotopic relationships (considered non-parametrically). In addition, visual regions had the highest explanatory power (i.e., largest regression coefficients). We also considered subject repeatability and found that the degree of repeatability seen in fully localized models is largely recovered using our proposed subject-level regression models. Further, even fully exchangeable models retain a sizeable amount of repeatability information, despite discarding all localization information. These results suggest the tantalizing possibility that fMRI connectivity analysis can be performed in subject-space, using less aggressive registration, such as simple affine transformations, multi-atlas subject-space registration, or perhaps even no registration whatsoever.