The Study Of Brain Function And The Neural Mechanisms Of Repetitive Transcranial Magnetic Stimlation In Parkinson’s Disease Patients With Depression Based On Resting State Functional Magnetic Resonance Imaging

Objective:This research was conducted to analyze the brain function characteristics of Parkinson’s disease(PD)patients with depression(DPD)from the local and brain network level,and investigate the changes in brain function of DPDpatients before and after repetitive transcranial magnetic stimulation(rTMS),so as to provides a certain scientific basis for further exploration of the pathogenesis and standardizing the diagnosis and treatment program in DPD.Method:Based on the technology of resting-state functional magnetic resonance imaging(rs-fMRI),Regional homogeneity analysis(ReHo)and the theory of complex network were used to analyze the difference of synchronicity of neuronal activity and brain network topological properties among DPD,PD patients without depression(NDPD)and Healthy Subjects(HCs).In addition,the network based statistical analysis(NBS)method was used to investigate the differential connections in the brain networks between DPD and NDPD.On this basis,a pilot study was conducted using ReHo to explore the changes of brain function in DPD patients after high frequency rTMS on the left dorsolateral prefrontal cortex(DLPFC).Results:In patients with DPD,The ReHo of the left median frontal gyrus was significantly increased,while the ReHo of the right triangle inferior frontal gyrus was significantly decreased.At the same time,it was found that the ReHo were significantly increased in the motor cortex,including the right precentral gyrus,left supplementary motor area and right paracentral lobule.The limbic system(including the right median cingulate and paracingulate gyri,left anterior cingulate gyrus and left insula),bilateral precuneus and occipital lobe all had abnormal spontaneous activity of the neurons.In addition,the severity of depression was significantly correlated with the ReHo values of the regions which were almost the same as the brain areas above with abnormal ReHo.Most brain regions above were monoaminergic neurotransmitter projection areas.(2)The DPD,NDPD and HCs groups all had the "small world" attribute,but there was no significant statistical difference among the groups.Compared with NDPD group and HCs group,DPD group had multiple missing hub nodes in the left posterior cingulate gyrus and the temporal lobe,including bilateral middle temporal gyrus,fusiform gyrus and right subtemporal reglion,mainly in the key brain areas of auditory and visual pathways.Otherwise,the regions with abnormal node efficiency of DPD were mainly concentrated in the prefrontal and temporo-occipital lobes.Partial correlation analysis showed that node efficiency of the prefrontal and temporo-occipital lobes was significantly correlated with the severity of depression in PD patients.Beyond all that,Compared with the NDPD group,the DPD group showed abnormal reduced connections among multiple brain regions in the prefrontal lobe,temporal lobe,and limbic system,but only increased connections between individual brain regions.The brain regions above with abnormal topological properties and functional connections were mostly located in the default mode network(DMN),central executive network(CEN)and salience network(SN),as well as the key nodes of auditory and visual pathways.(3)Compared with before treatment,the depressive score of DPD patients after treatment showed different degrees of decrease.Meanwhile,the ReHo of bilateral frontal lobe,left orbital middle frontal gyrus,right superior temporal gyrus,right lenticular nucleus and putamen,right anterior cingulate gyrus,left piriform cortex and cerebellar vermis were significantly increased.Conclusions:(1)The occurrence and development of DPD were correlated with the dysfunction of local brain regions,and these changes might be due to the degenerative changes of monoaminetic system in PD.(2)Information transmission of DPD brain network still maintained the optimal balance between local optimization and global integration,but the information transmission among local brain regions was has been blocked.Abnormal function of key brain regions in DMN,CEN and SN circuits and damage of the integrity of the circuits might be the key pathophysiological basis for DPD.Meanwhile,the abnormalities in the relevant brain regions of auditory and visual pathways might play a key role in the functional integration of DPD brain networks.However,the causal relationship between the auditory and visual dysfunction and DPD should be clarified in further studies.(3)Repetitive transcranial magnetic stimulation not only produced local effect on the target site,but also distant effect on the other brain regions,which might play a role in the treatment of DPD by adjusting the abnormal functional state of brain regions and brain networks.