Measuring functional connectivity in stroke: approaches and considerations

Recent research has demonstrated the importance of global changes to the functional organization of brain network following stroke. Resting functional MRI (R-fMRI) is a non-invasive tool that enables the measurement of functional connectivity (FC) across the entire brain while placing minimal demands on the subject. For these reasons, it is a uniquely appealing tool for studying the distant effects of stroke. However, R-fMRI studies rely on a number of premises that cannot be assumed without careful validation in the context of stroke. Here, we describe strategies to identify and mitigate confounds specific to R-fMRI research in cerebrovascular disease. Five main topics are discussed: 1) achieving adequate co-registration of lesioned brains, 2) identifying and removing hemodynamic lags in resting BOLD, 3) identifying other vascular disruptions that affect the resting BOLD signal, 4) selecting an appropriate control cohort, and 5) acquiring sufficient fMRI data to reliably identify FC changes. For each topic, we provide evidence-based guidelines for steps to improve the interpretability and reproducibility of FC-stroke research. We include a table of confounds and approaches to identify and mitigate each. Our recommendations extend to any research using R-fMRI to study diseases that might alter cerebrovascular flow and dynamics or brain anatomy.