Preserved higher-order mentalising during strategic interactions after medial prefrontal cortex damage

Mentalising, the ability to infer the beliefs and intentions of others, is essential for successful social interaction. Previous studies have implicated the medial prefrontal cortex in mentalising, but whether this region is necessary for higher-order mentalising remains unclear. Here we show that people with focal damage to the medial prefrontal cortex retain the ability to engage in higher-order mentalising during a strategic social game.

We compare their performance with patients with brain damage in other regions and lesion-free participants. Individuals with medial prefrontal cortex damage achieve similar rewards and use comparable mentalising strategies, but they are slower when making strategic decisions. Computational modelling indicates that this slowing reflects a greater tendency to require evidence before committing to a choice.

Voxel-based lesion-symptom mapping identifies medial prefrontal regions linked to altered decision processes rather than mentalising. These findings suggest that the medial prefrontal cortex supports strategic decisions while higher-order mentalising remains intact. We would like to thank Prof.

Matthew Rushworth and Prof. Molly Crockett for their insightful comments and useful discussions and Ayat Abdurahman, Luca Hargitai and Daniel Drew for assistance with data collection. Lockwood discloses support for the research of this work from Medical Research Council Fellowship (MR/P014097/1 and MR/P014097/2), a Christ Church Junior Research Fellowship, a Christ Church Research Centre Grant, a Jacobs Foundation Research Fellowship, a Leverhulme Prize (PLP-2021-196), a Wellcome Trust/Royal Society Sir Henry Dale Fellowship (223264/Z/21/Z) and a UKRI EPSRC Frontiers Research Guarantee/ERC Starting Grant (EP/X020215/1).

Ruff was supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 725355, ERC Consolidator grant BRAINCODES), the University Research Priority Programme ‘Adaptive Brain Circuits in Development and Learning’ (grant no. URPP AdaBD) at the University of Zurich, and the Swiss National Science Foundation (grant nos. 10006863 and 100019L-173248). S.G.M. was supported by MRC grant UKRI2552 and by the National Institute of Health and care Research (NIHR) Oxford Biomedical Research Centre (BRC).

M.H. was supported by the Wellcome Trust. S. was supported by funding from the Ministry of Education in Taiwan. M.A.J.A was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/R010668/2), a Jacobs Foundation Fellowship and a Wellcome Trust Discovery Award.