One ring to rule them all: the unifying role of prefrontal cortex in steering task-related brain dynamics

Surviving and thriving in a complex world require intricate balancing of higher order brain functions with essential survival-related behaviours. Exactly how this is achieved is not fully understood but a large body of work has shown that different regions in the prefrontal cortex (PFC) play key roles for diverse cognitive and emotional tasks including emotion, control, response inhibition, mental set shifting and working memory. We hypothesised that the key regions are hierarchically organised and we developed a framework for discovering the driving brain regions at the top of the hierarchy, responsible for steering the brain dynamics of higher brain function. We fitted a time-dependent whole-brain model to the neuroimaging data from large-scale Human Connectome Project with over 1000 participants and computed the entropy production for rest and seven tasks (covering the main domains of cognition). This thermodynamics framework allowed us to identify the main common, unifying drivers steering the orchestration of brain dynamics during difficult tasks; located in key regions of the PFC (inferior frontal gyrus, lateral orbitofrontal cortex, rostral and caudal frontal cortex and rostral anterior cingulate cortex). Selectively lesioning these regions in the whole-brain model demonstrated their causal mechanistic importance. Overall, this shows the existence of a 'ring' of specific PFC regions ruling over the orchestration of higher brain function.
G.D. is supported by the Human Brain Project Specific Grant Agreement 3 Grant agreement no. 945539 and by the Spanish Research Project AWAKENING: using whole-brain models perturbational approaches for predicting external stimulation to force transitions between different brain states, ref. PID2019–105772GB-I00/AEI/10.13039/ 501100011033, financed by the Spanish Ministry of Science, Innovation and Universities (MCIU), State Research Agency (AEI). Y.S.P is supported by European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant 896354. E.T is supported by grants PICT-2018–03103 and PICT-2019–02294 funded by Agencia I+D+I (Argentina) and by a Mercator fellowship granted by the German Research Foundation. M.L.K. is supported by the Centre for Eudaimonia and Human Flourishing (funded by the Pettit and Carlsberg Foundations) and Center for Music in the Brain (funded by the Danish National Research Foundation, DNRF117).
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