Unveiling the functional specialisation of human white matter circuits with naturalistic stimuli

Functional MRI (fMRI) has traditionally focused on grey matter activations, overlooking the contribution of white matter pathways to brain organisation. Yet evidence suggests that white matter constrains, modulates, and integrates signals across distant regions. Here, we introduce a framework to map the functional specialisation of white matter circuits using fMRI scans collected while participants watched naturalistic videos.

By leveraging ecologically valid stimuli, this method captures cognition as it naturally unfolds. Integrating fMRI with brain connections, we derived a functionally grounded parcellation of the connectome, challenging conventional cortical-based cognitive taxonomy. Distinct cognitive profiles emerged for association and commissural fibres, with association pathways preferentially linked to language-related processes and commissural pathways to executive and motor functions, affirming the functionally heterogeneous nature of white matter systems.

An artificial intelligence framework applied to independent datasets confirmed the robustness and functional relevance of the identified parcels. This open-access framework also enables the interactive exploration of white matter functional organisation, offering a new lens on the neural bases of cognition. The authors would like to thank Hervé Lemaitre for his essential support with computational and informatics aspects of this work.

We also thank all members of the Brain Connectivity and Behaviour Laboratory and the Groupe d’Imagerie Neurofonctionnelle for the input and discussions on the study. We are very grateful to everyone who helped reenact and perform the different scenes used to create the movie stimuli illustrated in Figs. 3 and 4. Finally, we thank the reviewers for the helpful comments.

M.T.d.S. is supported by HORIZON-INFRA-2022 SERV (Grant No. 101147319) ‘EBRAINS 2.0: A Research Infrastructure to Advance Neuroscience and Brain Health’, by the European Union’s Horizon 2020 research and innovation program under the European Research Council (ERC) Consolidator grant agreement No. 818521 (DISCONNECTOME), the University of Bordeaux’s IdEx ‘Investments for the Future’ program RRI ‘IMPACT’, ANR-26-CE37-4617-01 PRECOG, and the IHU ‘Precision & Global Vascular Brain Health Institute(VBHI)’ funded by the France 2030 initiative (ANR-23-IAHU-0001). V.P. is supported by IHU ‘Precision & Global Vascular Brain Health Institute(VBHI)’ funded by the France 2030 initiative (ANR-23-IAHU-0001). These authors contributed equally: V.

Brain Connectivity and Behaviour Laboratory (BCBlab), Bordeaux, France M. Thiebaut de Schotten Groupe d’Imaginerie Neurofonctionelle (GIN), Institut des Maladies Neurodégénératives (IMN), UMR 5293, CNRS, CEA, Université de Bordeaux, Bordeaux, France M. Thiebaut de Schotten IUSS Cognitive Neuroscience (ICON) Center, Scuola Universitaria Superiore IUSS, Pavia, Italy Correspondence to M.