The Biomarker Of Subtypes And Progression On Parkinson's Disease:A Functional MRI Study

BackgroundIdiopathic Parkinson's disease(PD)is the second most common neurodegenerative disease.It shows obvious heterogeneous in motor manifestation and disease progression.However,to data,the reasons of these heterogeneous are still not well understood.Therefore,we firstly explored the target making significant influence on PD different motor phenotype,and then longitudinally evaluated the alteration of the brain activity in PD patients.MethodsStudy 1:79 PD patients(43 TD and 36 PIGD)and 31normal controls(NC)were recruited and compared the grey matter volume and perfusion characteristics within the thalamus between PD phenotypes.Granger causality analysis(GCA)was used to compare the causal connectivity between different subtypes.Study2:Resting-state fMRI data were acquired from 27 normal controls and 23 PD patients at baseline and follow-up.Regional homogeneity(ReHo)and voxel-based-morphometry(VBM)were used to identify local spontaneous brain activity differences and grey matter volume respectively.ResultsStudyl:There was an increased gradient perfusion among three groups(TD>PIGD>NC)in the ventral intermediate nucleus(Vim),where perfusion was positively correlated with clinical tremor scores.GCA revealed that TD patients had enhanced causal connectivity from bilateral Vim to bilateral paracentral,Ml and cerebellum compared with NC.PIGD subtype revealed increased causal connectivity from bilateral Vim to bilateral pre-motor cortex and putamen.What's more,there were positive correlations between tremor scores and causal connectivity from the Vim to cerebellum.Patients with higher connectivity(from right Vim to right precentral and right putamen)showed higher clinical PIGD scores.Study2:We observed progressive decreased ReHo in the sensorimotor cortex,the default module network and the left cerebellum,while continuous increased ReHo in supplementary motor area,bilateral temporal gyrus and hippocampus with progression of disease.Moreover,there was significant positive correlation between the rates of ReHo change in the left cerebellum and the rates of the UPDRS-III scores change.VBM showed there was no difference in grey matter volume among the three groups.ConclusionStudyl:This multilevel analysis showed that the core pathophysiology in TD subtype may lay in the Vim,and a differential causal connectivity pattern exist in TD and PIGD-related networks that relate to behavioral heterogeneity in PD.Study2:we observed both compensatory mechanisms(the SMA,bilateral temporal gyrus,bilateral hippocampus and cerebellum)and loss of efficiency(the SMC and the DMN)occurred with disease progression.These findings provided longitudinal alterations of the local spontaneous brain activity in PD.