RESUMO
Background: 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. Analysis methods can come in the form of one-edge-at-a-time analyses or dimension reduction/decomposition methods. Common to these approaches is an assumption that brain regions are functionally aligned across subjects; however, it is known that this functional alignment assumption is often violated. Methods: In this paper, we use subject-level regression models to explain intra-subject variability in connectivity. Covariates can include factors such as geographic distance between two pairs of brain regions, whether the two regions are symmetrically opposite (homotopic), and whether the two regions are members of the same functional network. Additionally, a covariate for each brain region can be included, to account for the possibility that some regions have consistently higher or lower connectivity. This style of analysis allows us to characterize the fraction of variation explained by each type of covariate. Additionally, comparisons across subjects can then be made using the fitted connectivity regression models, offering a more parsimonious alternative to edge-at-a-time approaches. Results: We apply our approach to Human Connectome Project data on 268 regions of interest (ROIs), grouped into eight functional networks. We find that a high proportion of variation is explained by region covariates and network membership covariates, while geographic distance and homotopy have high relative importance after adjusting for the number of predictors. We also find that the degree of data repeatability using our connectivity regression model-which uses only partial location information about pairs of ROI's-is comparably as high as the repeatability obtained using full location information. Discussion: While our analysis uses data that have been transformed into a common template-space, we also envision the method being useful in multi-atlas registration settings, where subject data remains in its own geometry and templates are warped instead. 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.
RESUMO
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.