Unveiling the functional specialisation of human circuits with naturalistic stimuli

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Abstract

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 constraints, 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, affirming the functionally heterogeneous nature of white matter systems. A novel 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.

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