Complex interplay between structural and functional brain connectivity in acallosal BTBR T+tf/J mice

Introduction Recent investigations of the relationship between functional and structural connectivity in healthy brain support the notion that correlations in spontaneous brain activity reflect patterns of anatomical connectivity (1, 2). However, studies examining congenital or surgical alteration of the corpus callosum (i.e. the main direct structural connection between the two cerebral hemispheres) have produced conflicting results which somewhat challenge this view. For example, preserved inter-hemispheric connectivity in individuals with callosal agenesis has been recently described (3), in contrast with previous reports in humans (4, 5) and surgical callostomy studies in non human primates (6). These results highlight a complex (and still elusive) interplay between structural connections and functional networks that is apparent in acute or congenital neurological states characterized by large white matter topological alterations. In order to better elucidate this relationship, here we used DTI tractography and resting-state fMRI (rsfMRI) to probe structural and functional brain connectivity in BTBR T+tf/J mice, a congenital acallosal mouse line widely used in the preclinical community to mimic autism-like symptoms owing to its robust communication and social deficits (7). Normo-callosal C57Bl6/J mice were used as comparators owing to their recently characterized rsfMRI connectional signature (8).