Analysis Of Brain Network In Parkinson's Disease With Wearing-off: A Magnetic Resonance Imaging Study

ObjectivesAs disease progressed,PD patients will encounter motor complications such as wearing-off,of which prevalence could be higher than 50% more than five years after diagnosis.However,the underlying mechanism of wearing-off is still unclarified.This is a study aming at:(1)search for clinical risk factors in PD patients with wearing-off and substantial difference in brain function and structures,(2)detect alterations of dynamic functional network and efficiency of brain activity in PD patients with wearing-off,(3)investigate the effect of dopaminergic medications on brain dynamic functional network in PD patients with wearing-off.Contents and methodsExperiment 1: we have enrolled PD patients and divide them into PD patietns with wearing-off(PDWO)and PD patients without wearing-off(PDn W),along with matched healthy controls(HC).All clinical features and T1 weight images,functional magnetic resonance(MR)images,diffusion tensor images are acquired.Functional network construction and metrics of network topology,voxel-based morphometry and tract-based spatial statistics are applied to detect differences between groups.Correlation between distinct metrics and clinical features is also analysed.Experiment 2: PD patients(PDWO and PDn W)and HC are selected.All clinical features are collected and functional MR images are acquired in all subjects.Independent components are extracted in all functional MR images across all participants by independent component analysis.Functional matrices are constructed based on the independent components as regions of interest in every subject and then classified into distinct functional state.Temporal variants and network topology efficiency are analysed from all sujects and compared between groups.Experiment 3: PDWO and PDn W are included.All clinical features are collected and functional MR images are acquired before and after taking dopaminergic medication in all subjects.With pipelines of seed(putamen)to voxel manpping,dynamic functional network construction,cluster analysis and temporal variants and topology efficiency calculation,distinct metrices are identified between groups,along with partial correlation with clinical featurs.Innovative resultsWith PDWO,PDn W and HC cohort established,this study applied multy-modal MRI,dynamic functional connectivity analysis and dopaminergic medication.The findings are as follows:(1)dysfunction of supramarginal gyrus and decrease of plasticity of precentral gyrus may relate with WO;(2)The pattern of dynamic functional connectivity and dwell time of PDWO differed from PDn W and HC,with which dose of dopaminergic medication correlated;(3)the abnormal patter of dynamic functional connectivity of PDWO could be mitigated by taking dopaminergic medication.The findings demonstrated the aberrant functional connectivity related with WO,abnormal dynamic functional connectivity pattern and compensatory effect of dopaminergic medications.Theoretical and practical significanceThis study combined multy-modal MRI and dynamic functional connectivity analysis with wearing-off and dopaminergic medication.The results implicated: supramarginal and precentral gyri might be involved in the development of wearing-off,the connectivity pattern might be denser in PDWO.These findings provided novel evidences to shed lights on mechanism and therapeutic target of wearing-off.Moreover,the compensatory effect of dopaminergic medication on aberrant pattern of dynamic functional connectivity in PDWO was noticed.With amelioration of drugs on wearing-off,our results suggested the dosage of medication was correlated with connectivity dwell time,which might be instructive for prescribing dopaminergic medications.