The Effect Of RTMS On The Symptoms Of Parkinson's Disease And Its Neural Mechanism

Background Parkinson's disease is a common neurodegenerative disease,with typical clinical symptoms including tremor at rest,rigidity,akinesia and postural/gait instability.It is also associated with non-motor symptoms such as sleep disorder,olfactory dysfunction and cognitive impairment.Levodopa has significant effect on early PD patients,but as the disease progresses the therapeutic effect decreases gradually.Deep brain stimulation is also a effective treatment for PD patients,but it is limited due to its invasive and surgical risk.Repetitive transcranial magnetic stimulation(rTMS)is a green,safe,noninvasive and painless neuromodulation technique that can be used to modulate the neuronal activity of the stimulation site to achieve therapeutic effect.In recent years,there had been many researches on rTMS for PD.The sequence parameters and target positions for different researches were various.Therefore,therapeutic effects of the treatment and the mechanisms of the treatment are still not clear.With the development of neuroimaging techniques,it provides a new technical for us to investigating the pathogenesis of PD.VBM and FCS analysis based on the rs-fMRI data can effectively describe the brain structure and functional changes of PD,and revealing the potential neural mechanism of intervention.Objective By optimizing the stimulus parameters and combining with magnetic resonance technique,this study is to observe the therapeutic effect of rTMS on PD,and explore the underlying neural mechanisms.(1)Previous studies have suggested that the therapeutic effect depend on the stimulus pattern.By comparing the efficacy of rTMS with different stimulus patterns,the first study is to optimize the stimulus parameters and apply it to the treatment of PD.(2)On the basis of the first study,the second study applys the optimized stimulus parameters to treat PD,observe its effects on improving motor symptoms and cognitive function,and explore the potential neural mechanism.Methods(1)By stimulating the supplementary motor area with 5Hz rTMS?25Hz rTMS? iTBS and sham stimulus,the first study compares the SSRT of SST in order to observe the intervention effect of different stimulus patterns and then select optimized stimulation pattern.(2)On the basis of the first study,by combining the navigation guidance system with the magnetic resonance technology,the second study employs the optimized stimulus pattern over the left supplementary motor area of PD in order to observe the effects of rTMS on improving motor symptoms and cognitive function,as well as to explore the potential neural mechanism of rTMS for PD.Results(1)Although the SSRT before the stimulus have no significant differences between the different stimulus patterns,the SSRT after iTBS decreased significantly.There is a significant difference between iTBS and sham stimulus,the intervention effect of iTBS is remarkable.(2)The UPDRS motor part score of PD significantly reduced after real rTMS treatment.After treatment,there are significant gray matter density differences in bilateral thalamus,left superior temporal gyrus,left insula and left supplementary motor area between real and sham group.FCS results indicate that there are significant functional connectivity differences in insula,supramarginal gyrus,inferior parietal lobule,supplementary motor area,premotor area and fusiform gyrus between real and sham group.Correlation analysis showed that the increased gray matter density of left thalamus positively correlated with the improvement of symptoms,the decreased gray matter density of left superior temporal gyrus and left supplementary motor area positively correlated with the improvement of symptoms,the decreased functional connectivity of insula,supramarginal gyrus,supplementary motor area and premotor area negatively correlated with the improvement of symptoms,the increased functional connectivity of fusiform gyrus positively correlated with the improvement of symptoms.Conclusion(1)The TBS stimulus pattern has good intervention effect,which can be used to treat PD and various diseases.(2)The PD patients achieved significantly therapeutic effects after being stimulated the left supplementary motor area by rTMS.The underlying neural mechanisms may be due to the change of the gray matter density of left thalamus and left supplementary motor area,as well as the dysconnection of thesupplementary motor area,insula,fusiform gyrus and other brain function networks.