Visual Tracking Abnormalities In Synucleinopathies

PURPOSE: 1.Explore whether idiopathic rapid eye movement sleep behavior disorder(iRBD),Parkinson disease(PD)and multiple system atrophy(MSA)had visual tracking abnormalities,and compare the characters of visual tracking abnormalities in iRBD,PD and MSA.2.Evaluate the possibility of visual tracking task as a diagnosis tool for PD and MSA.3.Assess whether there was dopaminergic system dysfunction of basal ganglia in iRBD patients,and was the visual tracking abnormalities correlated with the dopaminergic system dysfunction.4.Explore whether there was pedunculopontine nucleus-based function connectivity(FC)abnormalities in iRBD and PD patients,and was the visual tracking abnormalities correlated with FC abnormalities.PATIENTS AND METHODS: 1.We recruited age,sex matched iRBD,PD,MSA patients and healthy control(HC)to perform visual tracking task.10 oculomotor metrics were obtained from the task to assess participants' visual tracking performance.A multi-dimension vector called the Impairment Index was computed by combining all 10 oculomotor metrics,so that a better description of general visual tracking process was done.We analysed data using univariate and multivariate general linear model.2.The area under the curve(AUC)of the receiver operating characteristic(ROC)was calculated to evaluate the Impairment Index as a tool for differentiating iRBD,PD,MSA and HC group.3.Some iRBD patients underwent Dopamine transporter-single photon emission computed tomography(DAT-SPECT)to detect the DAT uptake of right/left striatum in the basal ganglia region 4.Some iRBD and PD patients underwent rest state-functional magnetic resonance imaging(rs-f MRI)and PPN-based whole brain FC analysis was used to explore differences among participant groups.Pearson r correlation analysis was used to explore whether visual tracking metrics was correlated to abnormal FCs.RESULTS: 1.iRBD patients had visual tracking abnormaliteis.The visual tracking dysfunction of iRBD patients was mainly in the initiation pursuit stage,including prolonged latency and decreased acceleration.The visual tracking dysfunction of PD was worse than that of iRBD,reflecting in the both initiation pursuit and steady-state tracking stage,including prolonged latency,decreased gain and decreased proportion of smooth pursuit.MSA patients performed worst in visual tracking task,covering all kinds of visual tracking abnormalities which iRBD and PD had.2.The Impairment Index that combines all 10 oculomotor metrics of the visual tracking task distinguished iRBD(AUC=0.74),PD(AUC=0.74)and MSA(AUC=0.93)from HC with both high specificity and sensitivity.Moreover,the Impairment Index discriminated MSA from PD(AUC=0.76)with high sensitivity and specificity.3.Some iRBD patients had decreased DAT striatal uptake indicating basal ganglia region dopaminergic system dysfunction.4.We found the FCs of PPN and precentral gyrus,PPN and middle frontal gyrus,PPN and middle temporal gyrus,PPN and cuneus were altered in iRBD and PD groups.In iRBD group,there was a correlation between visual tracking metrics(latency and acceleration)and FC signal values of PPN and between the cuneus,precentral gyrus,and middle temporal gyrus.CONCLUSION: 1.Our study was the first to demonstrate the visual tracking impairments in iRBD patients worldwide.Also it is the first time to systematically assess the visual tracking function of PD and MSA patients in China.PD and MSA patients both had visual tracking dysfunction which were more severe than iRBD patients had.2.Visual tracking task could be a new,non-invasive,standard diagnosis tool for PD and MSA.3.iRBD patients had decreased dopaminergic system function in basal ganglia,it could be one of the underlying mechanisms of visual tracking dysfunction.4.In the assessment of PPN-based whole brain FC analysis in iRBD and PD patients,we found the FCs of PPN and multiple brain regions were altered,it could be one of the underlying mechanisms of visual tracking dysfunction.