Brain Structure And Functional Magnetic Resonance Imaging In Patients With Different Motor Subtypes Of Parkinson’s Disease

Objective:The clinical manifestations of Parkinson’s disease(PD)are highly heterogeneous,and the typical motor symptoms are slow movement,tremor,stiffness,and gait/postural disturbance.PD can be further divided into different motor subtypes based on these typical motor symptoms:tremor dominant(TD),postural instability/gait difficulty(PIGD),and mixed subtypes,different subtypes exhibit different clinical manifestations and prognosis.However,the pathophysiological mechanism between different subtypes of PD has not been elucidated.In recent years,the development of various neuroimaging techniques has provided new ideas for the study of neurodegenerative diseases.Therefore,this study intends to combine structural and functional imaging techniques to study the differences of different subtypes of PD.We first used Voxel-Based Morphometry(VBM)to study the gray matter volume(GMV)differences between different PD subtypes.On this basis,brain regions with GMV differences were used as seed points,we analysed the functional connectivity(FC)changes between the gray matter atrophy area and the whole brain,and the pathological mechanisms of different PD subtypes were analyzed in combination with brain structure and function studies.Methods: From January 2022 to December 2022,we recruited 108 patients with PD and 32 Healthy Controls(HC)in the Department of Neurology.The HC group consisted of healthy subjects matched for sex and age.We used the Movement disorder society-of the Unified Parkinson’s Disease Rating Scale(MDS-UPDRS)to divide PD patients into the tremor dominent group(TD)and the postural instability/gait difficulty group(PIGD).In our PD patients,mixed subtypes were not included in the final study due to the small number.We collected general clinical data of all study subjects,including demographic data such as gender and age,were collected,the course of disease,age of onset,medication use,smoking and drinking history,and previous medical history of all PD patients,and we calculated the Levodopa Equivalents Dose(LEED).Meanwhile,PD patients were evaluated by relevant scales,MDS-UPDRS and Hoehn-Yahr(H-Y)staging scale for motor symptoms and severity,and Montreal Cognitive Assessment scale(MOCA)for cognitive function,Non-Motor Symptom Assessment Scale(NMSS)was used for non-motor symptom assessment.All subjects underwent cranial three-dimensional T1 structural Imaging(3D-TIW)and Resting-State functional Magnetic Resonance Imaging(RS-f MRI)scans.On the MATLAB(2013b)platform,VBM method was used to analyze the gray matter volume difference of each group.Based on the gray matter volume analysis results,DPABI and SPM12 were used to analyze the FC difference between the groups.Results: 1.A total of 140 subjects were finally included in this study,including 108 PD patients(PIGD group: 64,TD group: 44 cases)and 32 cases of HC group.There were no statistical differences in gender and age among the three groups(p > 0.05).There were no statistical differences in age of onset,levodopa equivalent dose(LEED)between PIGD group and TD group.There were significant differences in disease duration,H-Y grade,UPDRS-III,MOCA,NMSS,HAMA,HAMD,PSQI,PDQ39 and FOG(p < 0.05).2.Compared with the HC group,the volume of the left anterior central gyrus,putamen and bilateral caudate decreased in the PIGD group;The volume of right cerebellar lobule VIII decreased in TD group.3.Compared with the TD group,the volume of the left superior frontal gyrus,middle temporal gyrus,right superior temporal gyrus and anterior cingulate gyrus decreased in the PIGD group,while the volume of the right putamen increased.4.Compared with the HC group,FC from the right caudate to the right cerebellar lobule VIII was significantly decreased in the PIGD group,FC from the left superior frontal gyrus was increased,and FC locally from the right caudate nucleus was significantly increased.The FC from the right cerebellum to the left Calcarine in TD group was significantly lower than that in HC group.5.Compared with the TD group,the FC in the left middle temporal gyrus to the right cerebellar Crus2 area in the PIGD group was significantly decreased,the FC in the left medial frontal gyrus to the vermis and the right cerebellar Crus1 area was significantly decreased,FC in the right superior temporal gyrus to the left angular gyrus was decreased,FC in the right anterior cingulate gyrus to the left inferior temporal gyrus was significantly decreased,FC in the right putamen to the right cerebellar lobule VI and the left angular gyrus was also significantly decreased in the PIGD group.On the other hand,in the PIGD group,FC of left middle temporal return to right inferior frontal gyrus and superior frontal gyrus increased significantly,FC of left superior frontal gyrus to left parietal gyrus increased,and FC of right superior temporal gyrus to right inferior frontal gyrus and supplementary motor area increased,in addition,FC of the right anterior cingulate gyrus to the right hippocampus and FC of right putamen to the right insula increased.Conclusions:1.The basal ganglia nucleus volume decreased in the PIGD group,and the right cerebellar volume decreased in the TD group.Compared with the TD group,PIGD group had more severe frontotemporal cortex atrophy.2.There were significant differences in functional connectivity between the two subtypes of patients.Postural gait abnormalities in PD patients were associated with differences in cortical to cortical functional connectivity,as well as decreased functional connectivity in cerebellum and increased functional connectivity in basal ganglia region.3.PD subtypes are caused by both structural and functional changes in the brain.Our results help to explain the pathological mechanism of different subtypes of PD,and further provide a basis for individualized treatment.