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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.

BackgroundTraditional measures of static functional connectivity may not completely re ect the dynamic neural activity of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). This study was aimed to investigate the dynamic changes of large-scale functional network connectivity in the temporal domain in PD patients with and without LID. MethodsUsing dynamic functional network connectivity (dFNC) analysis, we evaluated 41 PD patients with LID (LID group) and 34 PD patients without LID (No-LID group), on and off their levodopa medications. Group spatial independent component analysis, sliding-window approach and k-means clusters were employed. ResultsIn OFF phase, we found no differences between PD subgroups in temporal properties. In ON phase, compared than No-LID group, LID group occurred more frequently and dwelled longer in strongly connected State 1, characterized by strong connections between visual network (VIS) and other networks.When switching from OFF to ON phase, LID group occurred more frequently and dwelled longer in State 2 and occurred less frequently and dwelled shorter in State 3 (both states were strongly connected), while No-LID group occurred more frequently and dwelled longer in State 5 (weakly connected). Additionally, correlation analysis further demonstrated that the severity of dyskinesia was only associated with frequency of occurrence and dwell time in State 2, dominated by inferior frontal cortex in cognitive executive network (CEN), strongly connecting with sensorimotor network (SMN) and VIS. ConclusionsUsing dFNC analysis, we found that compared to those without LID, PD patients with LID may be involved in the superexcitation of VIS, as well as interconnections between CEN and SMN, VIS, having impact on inhibition of motor circuits. The dFNC analysis might provide new insights into the neural mechanisms of LID in PD.

Abnormal dopaminergic modulation of the cortico-basal ganglia motor loops results in the emergence of levodopa-induced dyskinesia (LID). We focused on alterations in the gray matter (GM) volume and the cortical thickness of the brain, especially in cortico-basal ganglia motor loops, in Parkinson’s disease (PD) with diphasic dyskinesia. 48 PD patients with diphasic dyskinesia, 60 PD patients without dyskinesia and 48 healthy controls (HC) were included. Voxel-based morphometry (VBM) was applied to get GM images from MRI brain images. FreeSurfer was used to get cortical thickness. Distinct analyses of covariance (ANCOVA) and linear contrasts were performed for early- and late-onset PD groups. The severity of diphasic dyskinesia was evaluated by the Unified Dyskinesia Rating Scale (UDysRS). Finally, the correlations between mean volumes of clusters showing differences and the UDysRS scores were performed by Pearson’s correlation. The GM volumes of precentral gyri were increased in PD patients with diphasic dyskinesia when compared with those without dyskinesia, which were positively correlated with UDysRS scores in PD patients with diphasic dyskinesia. However, there was no significant difference in cortical thickness among groups. The increased precentral gyri GM volumes might be associated with the pathogenesis and the severity of diphasic dyskinesia.

Impulse control disorders (ICD) in Parkinson’s disease (PD) might be attributed to misestimate of rewards or the failure to curb inappropriate choices. The mechanisms underlying ICD were reported to involve the lateralization of monoamine network. Our objective was to probe the significant role of lateralization in the pathogenesis of ICD. Twenty-one PD patients with ICD (PD-ICD), thirty-three without ICD (PD-no ICD), and thirty-seven healthy controls (HCs) were recruited and performed T1-weighted, diffusion tensor imaging (DTI) scans and resting state functional magnetic resonance imaging (rs-fMRI). By applying the Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer, we evaluated participants’ synchronicity of functional connectivity and structural changes between hemispheres. Also, tract-based spatial statistics (TBSS) was applied to compare fiber tracts differences. Relative to PD-no ICD group, PD-ICD group demonstrated reduced VMHC values in middle frontal gyrus (MFG). Compared to HCs, PD-ICD group mainly showed decreased VMHC values in MFG, middle and superior orbital frontal gyrus (OFG), inferior frontal gyrus (IFG) and caudate, which were related to reward processing and inhibitory control. The severity of impulsivity was negatively correlated with the mean VMHC values of MFG in PD-ICD group. Receiver operating characteristic (ROC) curves analyses uncovered that the mean VMHC values of MFG might be a potential marker identifying PD-ICD patients. However, we found no corresponding asymmetrical alteration in cortical thickness and no significant differences in fractional anisotropy (FA) and mean diffusivity (MD). Our results provided further evidence for asymmetry of functional connectivity in mesolimbic reward and response inhibition network in ICD.

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The characteristics of interhemispheric resting-state functional connectivity (FC) in Parkinson’s disease (PD) with fatigue remain unclear; therefore, we aimed to explore the changes in interhemispheric FC in PD patients with fatigue. Sixteen PD patients with fatigue (PDF), 16 PD patients without fatigue (PDNF) and 15 matched healthy controls (HCs) were enrolled in the retrospective cross-sectional study. We used voxel-mirrored homotopic connectivity (VMHC) to analyze the resting-state functional magnetic resonance imaging (fMRI) data of these subjects. Compared to PDNF, PDF patients had decreased VMHC values in the supramarginal gyri (SMG). Furthermore, the mean VMHC values of the SMG were negatively correlated with the mean fatigue severity scale (FSS/9) scores (r = −0.754, p = 0.001). Compared to HCs, PDF patients had decreased VMHC in the SMG and in the opercular parts of the inferior frontal gyri (IFG operc). The VMHC values in the IFG operc and middle frontal gyri (MFG) were notably decreased in PDNF patients compared with HCs. Our findings suggest that the reduced VMHC values within the bilateral SMG may be the unique imaging features of fatigue in PD, and may illuminate the neural mechanisms of fatigue in PD.