Modulation Effects On Putamen Local Activity Induced By RTMS Targeting At Primary Motor Cortex

Background: Parkinson’s disease is a common neurodegenerative disorder with relatively high morbidity and disability rates among middle-aged and aged people.Dopaminergic agents and neurosurgery are two main treatment protocols for Parkinson’s disease.However,traditional treatment with dopamine not only causes serious side effects but also develops resistance along with time.Neurosurgery,although effective,patients with Parkinson’s disease may be discouraged from the high cost of it.In recent years,repetitive transcranial magnetic stimulation has been used widely in clinical trials as a non-invasive brain stimulation technique.Transcranial magnetic stimulation on primary motor cortex is shown to be effective for Parkinson’s disease treatment.However,its mechanism remains unclear.Meta-analysis studies showed that a key feature which distinguishes Parkinson’s disease patients from healthy people is the abnormal local activity of putamen.Therefore,it is important to investigate the influence of TMS on putamen local activity for understanding the mechanism of TMS treatment on Parkinson’s disease.Objective: Combining functional magnetic resonance imaging technique and transcranial magnetic stimulation technique to investigate the modulation effects on local activity in putamen induced by repetitive transcranial magnetic stimulation at primary motor cortex.Method: Forty healthy subjects were recruited in this study.The experiment was a single-blind,randomized within-subject design.Each subjects participated in three rTMS sessions on 3 different days with at least one week separation.Magnetic resonance imaging scanning was performed before and after each rTMS session.There were three stimulation condition: low frequency(1 Hz),high frequency(10 Hz)and sham stimulation.Stimulation intensity was determined as 100% resting motor threshold.Each rTMS session included 1800 pulses.Amplitude of low frequency fluctuation(ALFF)and percent amplitude of fluctuation(PerAF)were calculated for pre-and post-TMS fMRI scanning to capture the local activity changes of putamen.Functional connectivity of stimulation targets was also calculated for pre-rTMS and post-rTMS fMRI scanning.Results:(1)ANOVA results of ALFF and PerAF showed that both main effects of TMS and stimulation condition as well as interaction effects reached 0.05 significance level but failed to pass multiple comparisons correction.Post hoc paired t-tests results of PerAF revealed that significant changes within putamen mask(FDR correction,q=0.05)were only existed between 1Hz post-and pre-TMS.(2)We have not observed significantfunctional connectivity changes of stimulation targets.(3)After excluding non-responders,the results of responders replicated previous findings but with larger cluster volume.Conclusion: The results of this study showed that repetitive transcranial magnetic stimulation on the primary motor area can significantly change the local activity of putamen characterized by ALFF and PerAF,which may help understanding mechanism of transcranial magnetic stimulation in the treatment of Parkinson’s disease and promoting the clinical application of transcranial magnetic stimulation.