Unsupervised mapping of causal relations between brain lesions and behavior.

Human lesion studies offer one of the most direct routes to investigating the causal relations between brain regions and behavioral outcomes in circumstances where experimental interventions are highly restricted. However, these studies face a major challenge in identifying the right level of granularity at which brain regions and behavioral outcomes should be analyzed to identify the association between lesions to specific brain regions and specific behavioral outcomes. Here we showcase a novel data-driven approach, Causal Feature Learning (CFL), that learns the appropriate level of analysis and the relation between lesion and cognitive impairment at the same time. The method avoids specifying brain regions and specific outcome measures a priori, allowing for the discovery of new cross-cutting lesion-behavior maps. We show that CFL robustly recovers lesion behavior maps in a simulated dataset where Canonical Correlation Analysis fails to provide interpretable results. We then show that CFL recovers known lesion-behavior maps for language deficits and visuospatial processing using a large dataset of lesion subjects, and finally we illustrate how CFL can be used to identify new groupings of outcomes when mapping lesions to depression symptoms.