Resting State FMRI Of PPN Function Connectivity With The Whole-brain In Patients With Freezing Of Gait

Objective: To evaluate the effect of pedunculopontine nucleus(PPN)in function connectivity in the mechanism of gait disorder in Parkinson's disease with freezing of gait(PD-FOG)and Primary progressive freezing of gait(PPFG),and to compare the differences between them.Methods: We collected 11 parkinson's disease patients with freezing of gait,,included 11 patients with Parkinson's disease with freezing of gait(PD-FOG),10 patients diagnosed as Primary progressive freezing of gait(PPFG),and 25 matched PD patients without freezing of gait(PD-NFOG).All the subjects was evaluated by the Freezing of Gait Questionnaire(FOGQ),the Unified Parkinson's Disease Rating Scale ?(UPDRS?),the Unified Parkinson's Disease Rating Scale ?(UPDRS?),Minimum Mental State Examination(MMSE),the Hamilton Depression Scale(HAMD),and the Hoehn & Yahr Scale(HY)to find out movement,cognitive and emotional background.All subjects underwent a resting state functional MRI scan for 12 hours after taking medicine.We use SPM12 and DPABI software to process and analyze Image on Matlab platform,First of all,format conversion(DICOM format is converted to NIFTI format);then,removing the first 5 time points;time layer correction,head motion correction,manual adjustment of image,structural phase separation,Functional structure registration,and then spatial standardization,spatially normalizing of images to the standard brain space of the Montreal Institute of Neurology(MNI),followed by Gaussian smoothing with a full width of 4.0 mm,and appling of a temporal filter(0.01-0.1 Hz)to remove low-frequency drift and physiological high-frequency noise,at last,deleting time points.Functional connectivity with pedunculopontine nucleus(PPN)was analyzed.Seed to cluster analysis was performed at whole brain level and compared among three groups.Result: Age and gender,duration of disease,MMSE,and HAMD,UPDRS? were not significantly different among three groups.There was no significant difference in UPDRS? and H-Y staging between PD-FOG and PD-NFOG patients.There was no significant difference in FOGQ between the PD-FOG group and the PPFG group.The UPDRS? scores of the PD-FOG and the PD group was significantly higher than those of the PPFG group.The fMRI of whole brain function connectivity showed that compared with PD-NFOG,the right side PPN(PPN-R)was weakened in connectivity with the in the insular and cerebellum,and the fusiform and ParaHippocampal connections were enhanced in PD-FOG group;In PD-FOG the left side PPN(PPN-L)weakened connection with the thalamus and insula.Compared with PD-NFOG,in PPFG group PPN-R was weakened in connection with temporal lobe and enhanced in connection with the occipital lobe;And PPN-L weakened in connection with temporal lobe and enhanced in connection with cerebellum and frontal lobe.Compared with PD-FOG,in PPFG group,PPN-L increased the connection with temporal lobe,and weakened the connection between wedge and occipital lobe,and there was no significant difference in the functional connectivity of PPN-R between PPFG group and PD-FOG group.Conclusion The freezing of gait of PD and PPFG are related to the abnormal connection of PPN brain function,but the mechanism is different.The freezing of gait of Parkinson's disease is related to the weakened functional connection between the PPN-motor circuit(cerebellum,thalamus)and the sensory cortex(island,temporal lobe)and the enhanced connection of the PPN-limbic system(ParaHippocampus,fusiform).The mechanism of PPFG is mainly related to the weakening of the connection between the PPN and the sensory cortex(the temporal lobe,the occipital lobe,and the cuneus),but it has little to do with the functional connection of the PPN-motor circuit(cerebellum and thalamus).