Objective: To provide a novel neurobiological framework for understanding and predicting clinical trajectories in PKD.

Background: Paroxysmal kinesigenic dyskinesia (PKD) causes brief, movement-triggered dystonic or choreic attacks that can severely affect daily life. Though most patients eventually remit, timing and rate of improvement differ substantially across individuals, and predictive biomarkers remain lacking. Evidence indicates that PKD reflects distributed network dysfunction. However, how structural wiring supports or constrains these dysfunctions, evaluated by structure-function (SC-FC) coupling, remains unknown.

Method: Diffusion kurtosis imaging and resting‑state fMRI were acquired in 95 patients with PKD and 44 healthy controls (HCs). SC–FC coupling was quantified at nodal, intra‑network, and inter‑network levels. Patients were classified as remission or non‑remission. Machine-learning classifiers based on multilevel SC–FC features were trained to distinguish PKD from HCs and to predict remission status. Associations between SC–FC features and disease duration were assessed using Spearman correlation.

Results: Patients with PKD showed widespread SC–FC coupling abnormalities consistent with distributed rather than focal network dysfunction. Remission and non‑remission subgroups showed distinct SC–FC signatures, centering on cerebellar, somatomotor, and default‑mode systems. Machine‑learning classifiers discriminated PKD from HCs (AUC = 0.91) and remission from non‑remission (AUC = 0.95). Cerebellar–default‑mode network coupling was the top discriminative feature and correlated positively with disease duration (Spearman r = 0.35, p = 0.0027, FDR‑corrected).

Conclusion: Multilevel SC–FC coupling analyses reveal systems‑level abnormalities in PKD and suggest that partial normalization of coupling patterns accompanies remission. Cerebellar–default‑mode network coupling may serve as a sensitive imaging biomarker of remission status and disease progression, highlighting coupling‑based metrics as candidates for predicting PKD trajectory.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multilevel-structure-function-coupling-reveals-network-signatures-of-remission-in-paroxysmal-kinesigenic-dyskinesia/