AI Insight
Using electrical stimulation combined with functional MRI (es-fMRI) in epilepsy patients undergoing intracranial monitoring, researchers mapped direct axonal connections across the human cortex and compared them with functional brain organization. They found that anatomically connected regions tend to share similar functional profiles, that this functional similarity predicts connectivity three times better than physical distance alone, and that long-range connections are the most functionally specific. Notably, resting-state functional connectivity, a widely used indirect measure of brain organization, correlated only weakly with the direct anatomical connectivity measured by es-fMRI, suggesting these two methods capture fundamentally different aspects of brain organization.
Why it matters
Understanding which cortical regions are directly wired together, and why, is essential for building accurate models of how the brain computes and communicates, with potential implications for interpreting neurological and psychiatric disorders that involve disrupted connectivity. This work also establishes es-fMRI as a scalable method capable of producing human connectome data at a resolution previously only achievable in animal models using invasive tracer injections.
⚠️ Preprint – Noch nicht peer-reviewed
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The functional organization of human cortex has been mapped in considerable detail1-5, yet the axonal connections linking these areas remain largely unknown. This gap precludes inferring either the computational pathways through cortical networks or the principles governing why each area connects to its particular target regions. Here, in patients undergoing intracranial monitoring for epilepsy, we used concurrent electrical stimulation and functional magnetic resonance imaging (es-fMRI), validated previously against tracer studies in nonhuman primates6, to map anatomical connectivity of cortical sites across the whole brain, and combined these maps with task and resting-state fMRI in the same individuals. Es-fMRI revealed four main findings. First, connectivity followed an asymmetric functional-similarity principle: connected sites tended to share similar functional profiles, but, because connectivity is sparse, most pairs of functionally similar sites were not connected. Second, although connectivity also declines with distance7, the functional profile explained three times as much variance in connectivity as distance did, and long-range connections were the most functionally specific. Third, es-fMRI revealed direct monosynaptic links between established functional regions, including between the fusiform face area (FFA)2 and the temporoparietal junction (TPJ)3 for social cognition. Fourth, resting-state functional connectivity (rsFC) of a stimulation site was only weakly correlated with that site’s es-fMRI connectivity. Together, these results provide a first principled link between anatomical connectivity and functional organization in the human cortex, and establish es-fMRI as a scalable approach to building a tracer-grade connectome of the human brain.
Source: Monosynaptic connections link functionally similar regions in human cortex