Clinical Heterogeneity And Brain Functional Connectivity In Parkinson’s Disease With Subtypes Of Motor Symptoms Based On Resting-state Functional Magnetic Resonance Imaging

Parkinson’s disease(PD)is a neurodegenerative disease characterized by movement disorders.According to the characteristics of movement disorders,it can be divided into tremor dominant(TD)type,akinetic-rigid(AR)type,and postural instability gait difficulty(PIGD)type.There are differences in clinical phenotypes among patients with different motor subtypes of PD.In recent years,exploration and research on the clinical heterogeneity of different motor subtypes of PD have been ongoing.However,simultaneous analysis of three motor subtypes is rare,and the analysis methods are other,resulting in diverse conclusions that are difficult to apply to clinical practice.Therefore,based on the resting state functional magnetic resonance imaging(RS-f MRI)method,this article analyzes the brain functional activities of three types of PD motor subtypes,explores the functional connection mechanisms for the occurrence and development of the three types of motor subtypes,and seeks a clinical evaluation approach for the application of RS-f MRI method to PD motor subtypes,to achieve the purpose of identifying and diagnosing PD motor subtypes,and reduce the burden of disease.Part Ⅰ Study and analysis of clinical characteristics of different motor subtypes of PDObjective: To collect clinical data,analyze the degree of disease and other non-motor symptoms,comprehensively analyze the clinical characteristics of different motor subtypes of PD,and compare the results of brain function research to provide a clinical basis for brain function imaging analysis.Methods: The clinical information and UPDRS scores of 528 patients with PD were included,and their cognitive scale and non-motor scale scores were collected.Using improved grouping rules,PD patients were divided into TD,AR,and PIGD,which cannot be classified as unformatted according to the rules.Using SPSS statistical software to compare and analyze the clinical characteristics of patients with different motor subtypes.Results: 528 patients were divided into 146 cases of TD,110 cases of AR,241 cases of PIGD,and 33 cases of atypical type.There was no significant statistical difference in gender distribution and duration of disease among the four types of motor subtypes.Still,there was a significant statistical difference in age and onset age.The average age and onset age of patients with PIGD were older than those of all other subtypes.There were differences in the distribution proportions of the four groups of disease stages,and there was no significant statistical difference in the disease stages among the subgroups of patients.There are differences in the severity of motor disorders among the motor subgroups.Different motor subtypes have differences in the total scores of the UPDRS II Activity of Daily Living Scale and the UPDRS III Exercise Examination Scale,with lower scores for TD.There were differences in the scores of tremor,rigidity,and gait posture items between the motor subgroups.MMSE,Mo CA,NMSS,ESS,and PDSS have no significant differences among motor subtypes.NMSQ,HAMA,and HAMD have differences among motor subtypes,with PIGD being more severe.Conclusion: PD patients can be divided into TD,AR,and PIGD according to the characteristics of movement disorders,with a few not yet finalized.Compared with other subtypes,TD has mild motor symptoms and a relatively mild degree of illness.The onset and age of PIGD are older,and non-motor symptoms are more pronounced.AR can be distinguished from TD with severe motor symptoms,and from PIGD with mild and fewer non-motor symptoms.The atypical type may be a subtype of motor disorders between AR and PIGD.Part Ⅱ Regional homogeneity of PD motor subtypes based on resting-state functional magnetic resonance imaging Objective: To explore the regional homogeneity(Re Ho)of f MRI in different PD motor subtypes and provide evidence for the clinical application of Re Ho values.Methods: Collect clinical f MRI data of PD patients and healthy controls,and divide PD patients into TD group,PIGD group,and AR group using UPDRS score.Then,conduct data processing with REST Plus software,calculate the Re Ho value between each group,observe the regional homogeneity of brain function in each motor subtype and the different brain regions in healthy controls,and then analyze the different brain regions between each motor subtype.Finally,a correlation analysis was conducted between the Re Ho values of each of the most significantly other brain regions and clinical scale information.Results: There were 33 cases in the TD group,14 cases in the AR group,23 cases in the PIGD group,and 39 healthy controls.Except for the PIGD type,there were differences in gender composition among the other three groups,and all three groups of patients had inter group differences except for UPDRS III.Among the four groups,the Re Ho value increased in bilateral cerebellar area 8,bilateral middle occipital gyrus,left cortex around the talus fissure,right orbital middle frontal gyrus,right caudate nucleus,and right middle frontal gyrus.There was no statistical difference between the AR group and other group.Compared with the healthy control group,the Re Ho values in the right middle frontal gyrus,left inferior parietal marginal angular gyrus,right inferior temporal gyrus,and left cerebellar area 8 in the TD group decreased,while the Re Ho values in the bilateral supplementary motor area,left lenticular putamen,and right inferior frontal gyrus in the PIGD group decreased.Compared with the PIGD group,the Re Ho values in the right cerebellar area 1,bilateral middle temporal gyrus,right orbital middle frontal gyrus,and left middle frontal gyrus in the TD group decreased,while the Re Ho values in the bilateral supplementary motor area,right dorsolateral superior frontal gyrus increased.The Re Ho values of the right superior frontal gyrus,the left middle temporal gyrus,and the bilateral caudate nucleus were negatively correlated with the tremor item scores.The Re Ho values of the right superior frontal gyrus in the ankylosis item were the strongest,the Re Ho values of the bilateral caudate nucleus in the gait posture item were the strongest,the Re Ho values of the left middle temporal gyrus in the H-Y stage were the strongest,and the bilateral supplementary motor area was not related to the clinical scale.Conclusion:There is a significant difference in Re Ho values between TD type and PIGD type.The Re Ho values of TD type and PIGD type were significantly reduced compared to healthy controls,and the brain regions involved were different.The differences in AR type among healthy individuals,TD type,and PIGD type were not significant.The specific seed point Re Ho value may become a potential indicator for evaluating motor disorders in PD patients.Part Ⅲ Functional and effective connectivity of Re Ho difference brain regions among PD motor subtypesObjective: To clarify the interaction and causal relationship between the synchronous increase in brain functional activity and other brain regions,and to provide a relevant imaging basis for explaining the neural activity mechanisms of the three motor subtypes.Exploring the correlation between functional connectivity and clinical indicators.Methods: The regions of interest with different Re Ho values between TD and AR,TD and PIGD were used as seeds to explore the interaction of the whole brain with the seed.Firstly,the correlation coefficient between the sequence and time of the whole brain pair of seeds,namely functional connectivity(FC),is analyzed.Then conduct the Granger causality analysis(GCA)study on the two groups to clarify the effective connections between the whole brain and seeds.Finally,we extracted the z FC values of specific seed points from patients with PD motor subtypes and conducted correlation analysis with the motor scale.Results: Compared with the AR group,the FC values of the right orbital superior frontal gyrus,the left cerebellar area 1,the right thalamus,the right medial and paracingulate gyrus,and the left inferior parietal marginal angular gyrus in the TD group were significantly higher,and the FC values of the left straight gyrus,the left anterior cingulate gyrus,and the paracingulate gyrus were significantly lower.In TD group,the influence of the activity of the right superior occipital gyrus on the activity of seed point was reduced,and the influence of the mass activity of bilateral middle frontal gyrus,left lenticular putamen,left dorsolateral superior frontal gyrus,left anterior cuneate lobe,left angular gyrus,left supplementary motor area,right medial and paracingulate gyrus on the activity of seed point was significantly increased.The z FC value is moderately negatively correlated with the tremor score,and slightly positively correlated with the ankylosing score and H-Y staging.Compared with the PIGD group,the FC values of the left middle temporal gyrus,the right middle frontal gyrus and the right posterior central gyrus in the TD group increased,and the FC values of the left middle occipital gyrus,the left inferior parietal marginal angular gyrus,the left inferior frontal gyrus in the orbit,and the left inferior frontal gyrus in the insular region decreased.In TD group,the activity of the right caudate nucleus,the right middle frontal gyrus,and the left dorsolateral superior frontal gyrus had less influence on the activity of the seed point,while the activity of the right middle temporal gyrus had significantly increased influence on the activity of the seed point.The z FC value is moderately negatively correlated with tremor item scores,and slightly positively correlated with H-Y staging.There was no significant difference in functional connection and effective connection of bilateral caudate nucleus between AR group and PIGD group.The z FC value is moderately positively correlated with UPDRS II,UPDRS II+III,and gait posture scores.Conclusion: There are differences between the TD group and the AR group in the specific functional connection and effective connection of the Superior frontal gyrus of right orbit.There is a difference in functional connectivity at the left middle temporal gyrus between the TD group and the PIGD group,but there is no difference in effective connectivity.There was no significant difference in functional connectivity and effective connectivity between AR group and PIGD group in specific regions of bilateral caudate nucleus.The exploration of z FC values at specific seeds may become a new idea for the application of functional imaging to the classification of motor disorders in PD patients.