Motor-planning cerebello-cerebral network alterations in PRRT2-related paroxysmal kinesigenic dyskinesia

Emerging preclinical evidence suggests that the cerebellum plays a critical role in paroxysmal kinesigenic dyskinesia (PKD) associated with proline-rich transmembrane protein 2 (PRRT2) mutations. This study aimed to investigate the role of cerebello-cerebral network in PKD patients with PRRT2 mutations (PKD-M) and PKD patients with no PRRT2 mutations (PKD-N).

Resting-state functional magnetic resonance imaging scan was performed on 105 PKD patients (47 PKD-M and 58 PKD-N) and 62 healthy controls (HC). For seed-based functional connectivity (FC) analysis, the cerebellum was parcellated into 10 function-related regions through a functional atlas of the human cerebellum obtained by a multi-domain task battery. The cerebello-cerebral FC and regional homogeneity (ReHo) were examined using one-way analysis of covariance and two-sample t-test in PKD-M, PKD-N and HC.

PKD-M had increased FC between a motor-planning related cerebellar region (region 4) and the middle cingulate gyrus, compared to HC. While PKD-M had decreased FC between this region and the lingual gyrus, compared to HC. PKD-M had increased FC between another cerebellar region (region 8) and the right inferior temporal gyrus/right superior frontal gyrus, compared to PKD-N. Additionally, PKD-M had decreased ReHo in the pons and the cerebellum anterior lobe and increased ReHo in the right inferior temporal gyrus, compared to HC.

PRRT2 mutations may cause abnormalities in a motor-planning cerebello-cerebral network, which likely play a major role in the pathogenesis of PKD-M.