A rostral prefrontal mediolateral gradient predicts creativity in frontotemporal dementia

Creative thinking is a fundamental aspect of human cognition, enabling the production of novel and useful ideas. It is hypothesized to emerge from the binding and reconfiguration of existing knowledge, through the generation of remote semantic associations and their combination in original and meaningful ways, respectively supported by the default mode (DMN) and executive control (ECN) networks. At the crossroads of these two networks, the rostral prefrontal cortex (PFC) is proposed as a key hub for DMN-ECN interactions, possibly supporting the interplay between generative and combinatory creative processes. However, the specific contributions of its medial and lateral subdivisions to creativity remain unclear. In this study, we aimed to characterize the involvement of the rostral PFC in creative cognition through the lens of behavioural variant frontotemporal dementia (bvFTD), a relevant pathological model as it primarily affects the rostral PFC and alters intrinsic connectivity within the DMN and ECN. Using whole-brain voxel-based morphometry, we explored the brain regions critical for the generation and combination of remote semantic associates, respectively, but also for creative abilities, thought to involve both types of processes. Using resting state functional connectivity and gradient mapping techniques, we also explored functional connectivity profiles within the rostral PFC and how connectivity variations within this region predict creative performance. As a result, we found a critical role of the rostromedial PFC for generating remote semantic associations and of the rostrolateral PFC for combining semantic associates, while both regions were critical for creative abilities. Moreover, we showed that intrinsic connectivity of rostral PFC is organized along a mediolateral functional gradient, segregating the rostromedial PFC, connected to the DMN, and the rostrolateral PFC, connected to the ECN. Finally, we showed that the range of this functional gradient, representing the functional differentiation between the ECN and DMN, predicts creative abilities. Overall, this study advances our understanding of creative cognition, its relationships to the anatomical and functional organization of the prefrontal cortex, and its impairment in bvFTD.