Monosynaptic connections link functionally similar regions in human cortex

In a collaboration between the MIT McGovern Institute and MGH Neurosurgery, Rui Xu, Alan Bush, and colleagues used concurrent electrical stimulation and fMRI (es-fMRI) in patients undergoing intracranial monitoring to map, for the first time in humans, the monosynaptic connections of individual cortical sites across the whole brain. Connectivity followed an “asymmetric functional-similarity” principle: connected regions tend to share a functional profile, yet because connectivity is sparse, most functionally similar regions are not directly connected. Functional profile explained roughly three times more of the connectivity than distance did, and the method revealed direct links between established areas such as the fusiform face area and the temporoparietal junction for social cognition. The work establishes es-fMRI as a scalable route toward a tracer-grade connectome of the human brain. Read the preprint: https://doi.org/10.64898/2026.05.19.726279