Cerebello-thalamofrontal dysconnectivity in paroxysmal kinesigenic dyskinesia: A resting-state fMRI study

Abstract

Introduction: The pathophysiology of paroxysmal kinesigenic dyskinesia (PKD) remains elusive to date; however, several lines of evidence from neuroimaging studies suggest involvement of the basal ganglia-thalamocortical network in PKD. We combined fractional amplitude of low-frequency fluctuation (fALFF) and seed-based functional connectivity (FC) analyses in order to comprehensively investigate intrinsic brain activity alter-ations and their relationships with disease severity in patients with idiopathic PKD. Methods: Resting-state functional MRI data were obtained and processed in 34 PKD patients and 34 matched controls. fALFF and seed-based FC maps were computed and compared between patients and controls. Linear regression analysis was further performed between regional fALFF values or FC strengths and clinical parameters in patients. Results: PKD patients had a significant increase in fALFF in bilateral thalamus and cerebellum compared with controls. FC analysis seeding at the thalamic clusters revealed significant FC increases in motor cortex and supplementary motor area in PKD patients relative to controls. Longer disease duration was associated with increasing FC strength between the thalamus and motor cortex. Conclusion: We have provided evidence for abnormal intrinsic activity in the cerebello-thalamic circuit and increased thalamofrontal FC in PKD patients, implicating interictal cerebello-thalamofrontal dysconnectivity in the pathophysiology of PKD. Given the increasing FC strength in proportion to disease duration, the thalamo-frontal hyperconnectivity might reflect either a consequence of recurrent dyskinesias on the brain or an innate pathology causing dyskinesias in PKD.