Forceps minor control of social behaviour

The clinical work package of PRISM, a collaborative research project funded by the EU public-private Innovative Medicine Initiative, identified a transdiagnostic and pathophysiological relationship between default mode network (DMN) integrity and social dysfunction. For testing the causality between the quantitative variation in DMN integrity and social dysfunction, we developed a preclinical backtranslation approach for disturbing DMN integrity and applied cutting-edge technologies such as functional ultrasound imaging and automated analysis of social behaviour in groups of mice 5 . Here we show that focal demyelination in the DMN leads to a decrease in global DMN connectivity and subsequently to impaired social behaviour and increased anxiety in mice. Reversibility of these observations suggests that integrity of the forceps minor, a fibre tract connecting important regions of the DMN in the prefrontal brain, plays a significant role in social functioning. In summary, this back-translation study demonstrates a causal pathophysiological relationship between DMN integrity and social dysfunction. The findings can support precision psychiatry approaches for the development of effective treatment of social dysfunction.