Altered interhemispheric synchrony in Parkinson's disease patients with levodopa-induced dyskinesias

Abstract

Levodopa-induced dyskinesias are common motor complication of Parkinson's disease after 4-6 years of treatment. The hallmarks of dyskinesias include unilateral onset and the tendency to appear on the more affected body sides. There is a growing literature documenting the lateralization abnormalities are associated with the emergence of dyskinesias. Our investigation aimed to explore interhemispheric functional and its corresponding morphological asymmetry. A total of 22 dyskinetic patients, 23 nondyskinetic patients, and 26 controls were enrolled. Resting-state functional magnetic resonance imaging scans were performed twice before and after dopaminergic medication. Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer were employed to assess the synchronicity of functional connectivity and structural alternations between hemispheres. During OFF state, dyskinetic patients showed desynchronization of inferior frontal cortex (IFC) when compared to nondyskinetic patients. And during ON state, dyskinetic patients showed desynchronization of IFC and pre-supplementary motor area (pre-SMA) when compared to nondyskinetic patients. However, there was no corresponding significant asymmetries in cortical thickness. Moreover, the degree of desynchronization of IFC and pre-SMA in dyskinetic pateients during ON state were negatively correlated with the Abnormal Involuntary Movement Scale (AIMS) scores. Notably, among patients who showed asymmetrical dyskinesias, there was a significant negative correlation between VMHC values of IFC and dyskinesias symptom asymmetry. Our findings suggested that uncoordinated inhibitory control over motor circuits may underlie the neural mechanisms of dyskinesias in Parkinson's disease and be related to its severity and lateralization.

Keywords: Parkinson's disease.

Fig. 1. Statistical maps showing VMHC differences in different brain regions between three groups during ON and OFF phase, respectively.

The threshold for display was set to p < 0.01.

Fig. 2. Correlations between VMHC values and AIMS scores during ON phase within the LIDs patients.

Scatterplots demonstrated that there was a significant negative correlation between the mean VMHC values in the pre-supplementary motor area and AIMS scores in LIDs patients. Besides, a negative correlation was also found between the mean VHMC values in the inferior frontal cortex (pars triangularis) and AIMS scores. Abbreviations: VMHC: voxel-mirrored homotopic connectivity; AIMS: Abnormal Involuntary Movement Scale.

Fig. 3. Relation between LIDs symptoms asymmetry and VMHC values of IFC (pars triangularis) during ON phase.

Asymmetry of dyskinesias symptoms was determined by calculating the absolute value of the difference between the left and right scores evaluated by UDysRS-III subscores. There was a significant relationship between dyskinesias symptoms asymmetry and desynchronization of inferior frontal cortex (pars triangularis) in the two hemispheres. Abbreviations: VMHC: voxel-mirrored homotopic connectivity; UDysRS: Unified Dyskinesia Rating Scale.