Abnormal structural‒functional coupling patterning in progressive supranuclear palsy is associated with diverse gradients and histological features.

The anatomy of the brain supports inherent processes, fostering mental abilities and eventually facilitating adaptive behavior. Recent studies have shown that progressive supranuclear palsy (PSP) is accompanied by alterations in functional and structural networks. However, how the structure and function of PSP coordinates change is not clear, and the relationships between structural‒functional coupling (SFC) and the gradient of hierarchical structure and cellular histology remain largely unknown. Here, we use neuroimaging data from two independent cohorts and a public histological dataset to investigate the relationships among the cellular histology, hierarchical structure, and SFC of PSP patients. We find that the SFC of the entire cortex in PSP is severely disrupted, with higher coupling in the visual network (VN). Moreover, coupling differences in PSP follow a macroscopic organizational principle from unimodal to transmodal gradients. Finally, we elucidate greater laminar differentiation in VN regions sensitive to SFC changes in PSP, which is related mainly to the higher cellular density and smaller size of the internal-granular layer. In conclusion, our findings provide an interpretable framework for understanding SFC changes in PSP and provide new insights into the consistency of structural and functional changes in PSP regarding hierarchical structure and cellular histology.