Aberrant higher-order interactions in the caudate-supplementary motor area-circuit in the blepharospasm by edge-centric functional analysis.

BACKGROUND: Neuroimaging evidence suggests that the pathological alterations associated with blepharospasm (BSP) are not confined to a single brain region but involve large-scale brain networks. However, the higher-order interactions among connections within these networks remain poorly understood. This study proposes to use an edge-centric analytical approach combined with motif analysis to characterize abnormalities in information flow and functional integration in BSP brain networks. METHODS: Resting-state fMRI data were collected from 102 patients with BSP and 160 healthy controls (HCs). An edge-centric analytical framework was constructed and integrated with triadic motif analysis to characterize higher-order interaction patterns among connections within brain networks. RESULTS: In BSP patients, normalized entropy in the precuneus and network-level entropy in the cognitive control and default mode networks were significantly increased, with precuneus entropy positively correlated with symptom severity. BSP patients also showed stronger community similarity between the left caudate and supplementary motor area (SMA). Motif analysis revealed that, when the left caudate was the reference node, closed-loop motifs were over-expressed and negatively correlated with disease duration, whereas forked motifs were under-expressed. When the SMA was the second reference node, both closed-loop and forked motifs were over-expressed, with forked motifs positively correlated with disease duration, while L-shaped motifs were under-expressed. CONCLUSIONS: This study is the first to use edge functional connectivity combined with motif analysis to reveal abnormal higher-order interactions within the caudate-SMA-motor control circuit in patients with BSP, and it provides new perspectives for targeted circuit-based neuromodulation interventions.