Abnormal interhemispheric resting state functional connectivity in Parkinson\u2019s disease patients with impulse control disorders

Caiting Gan,Huimin Sun,Kezhong Zhang,Min Ji,Kewei Ma,Yongsheng Yuan,Lina Wang

doi:10.1038/s41531-021-00205-7

Caiting Gan, Huimin Sun + Show 5 more

Open Access

https://doi.org/10.1038/s41531-021-00205-7

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Abstract

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.

Highlights

Impulse control disorders (ICD), including pathological gambling (PG), binge eating (BE), compulsive shopping (CS), and hypersexuality (HS)[1], are reported in 6.1–31.2% of Parkinson’s disease (PD) patients[2], occurring primarily in patients treated with dopamine receptor agonists
The pathogenesis of ICD in PD patients remains unclear, emerging evidence supports that a complex multifactorial mechanism of serotoninergic and noradrenergic interaction was involved in the development of ICD, beyond the classical dopaminergic corticostriatal networks[4]
Correlation analysis showed a negative relationship between Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease rating scale (QUIP-RS) scores and mean Voxel-mirrored Homotopic Connectivity (VMHC) values of the middle frontal gyrus (MFG) in PD-ICD group (r = −0.625, p = 0.013, Fig. 2a), indicating that with the aggravation of ICD symptoms, the function coordination of the MFG became poorer

Summary

INTRODUCTION

Impulse control disorders (ICD), including pathological gambling (PG), binge eating (BE), compulsive shopping (CS), and hypersexuality (HS)[1], are reported in 6.1–31.2% of Parkinson’s disease (PD) patients[2], occurring primarily in patients treated with dopamine receptor agonists. A DATSCAN imaging research supported that ICD symptoms were linked to the disruption of asymmetric molecular frontostriatal network centered on left basal ganglia, fitting well with the effect of left-hemisphere activity during reward processing[9]. These above findings implied that the laterality of dopamine and serotonin network might have significant influence on ICD. We adopted a validated analysis approach named Voxel-mirrored Homotopic Connectivity (VMHC), which could detect the altered interhemispheric connectivity via quantifying functional connections between each voxel in one hemisphere and its corresponding voxel in the other[10] This is a wellestablished approach that has been widely applied in the studies of many diseases. Diffusion tensor imaging (DTI) was applied in our study to detect fiber tracts impairment

RESULTS

Gan et al 3

DISCUSSION

Findings

METHODS