Efficacy And Mechanism Of Intermittent Theta Burst Stimulation Combined With Electroacupuncture On Upper Extremity Motor Dysfunction After Stroke

Background:Motor dysfunction of upper limb often occurs after stroke,which seriously affects the quality of life of patients.Intermittent theta burst stimulation（i TBS）is a special paradigm of repetitive transcranial magnetic stimulation that can significantly increase cortical excitability and promote upper limb motor function with shorter intervention time and lower stimulation intensity.Electroacupuncture（EA）is widely used in clinical and scientific research for its standard repeatability and feasibility.Quchi（LI11）,Hegu（LI 3）,Zusanli（ST 36）and Yanglingquan（GB 33）are acupoints commonly used in the treatment of stroke hemiplegia.i TBS is a top-down neuromodulation,and electroacupuncture is based on bottom-up somatosensory stimulation.However,there is currently little literature on the effects and mechanisms of i TBS binding on cortical excitability.In this study,the effects of i TBS combined with electroacupuncture intervention on cortical excitability in healthy subjects and ischemic stroke patients were evaluated by electrophysiological,functional imaging,and behavioral indicators.The purpose is to provide a new idea for the rehabilitation of upper extremity motor dysfunction after stroke.PartⅠ.The effect and mechanism of i TBS combined with electroacupuncture in modulating the excitability of healthy human exercise cortexObjective:To investigate the effects of i TBS combining EA on cortical excitability in healthy subjects by measuring electrophysiological indicators and scanning functional magnetic resonance imaging（f MRI）.Methods:1)Electrophysiological trials:From July 2018 to February 2019,26 healthy subjects were recruited through posters,of which 4 were excluded,1 was shed,and 1 was removed.The study used 2（i TBS:real and sham stimuli）×2（EA:real acupuncture and sham acupuncture）×4（measurement time point:baseline,immediately after intervention,20 min after intervention,40 min after intervention）three-factor repeated measurement of within-subjects design.Each subject must participate in all 4 interventions（sham i TBS+sham EA;sham i TBS+real EA;real i TBS+sham EA;real i TBS+real EA）consisting of i TBS and EA.The sequential effects of subjects participating in the trial were balanced by randomization.Subjects were single-blind and evaluated by a third party.Each two interventions were separated by more than 5 days.Electrophysiological parameters were measured at four time points before and after each intervention to assess changes in cortical excitability.Statistical analysis was performed using a three-factor repeated measures analysis of variance,and a post-hoc test was performed using a Bonferroni-corrected paired-sample t-test.2)Functional imaging trials:After the completion of the electrophysiological trials more than 2 weeks,5 healthy subjects were randomly selected for task-based and resting-state f MRI scans,and analyzed in 4 cases（baseline;sham i TBS+real EA;real i TBS+sham EA）;real i TBS+real EA)two-handed task brain activation and local brain changes in neural activity,including Amplitude of Low Frequency Fluctuations（ALFF）,Regional Homogeneity（Re Ho）.Results:1)Results of electrophysiological trials:At baseline,there was no significant difference in MEP_{MT1m V} amplitude between the 4 groups（P>0.05）.The three-factor interaction of i TBS,EA,and time had a statistically significant effect on MEP_{MT1m V}（P<0.001）.When EA was sham,there was no interaction between i TBS and time（P>0.05）,and the main effects of i TBS and time were not statistically significant（P>0.05）.Compared with baseline,there was no significant change in the MEP_{MT1m V} amplitude at each time point after the intervention of the real i TBS group and the sham i TBS group（P>0.05）,and the difference between the real i TBS group and the sham i TBS group at each time point was also not statistically significant.When EA was real,the interaction between i TBS and time was statistically significant（P<0.001）.In the sham i TBS+real EA group,the MEP_{MT1m V} amplitudes of T0 and T20 were significantly lower than the baseline（P=0.001;P=0.006）;In the real i TBS+real EA group,the MEP_{MT1m V} amplitudes of T0,T20,and T40 were significantly higher than the baseline（P<0.001;P=0.001;P=0.021）.2)Results of functional imaging trials:A one-sample t-test of task-based f MRI showed that the number of voxels activated in the right brain motor area is greater than in the left brain motor area at baseline;After real i TBS+real EA,the activation of both hemispheres was significantly higher than the baseline,which was consistent with the electrophysiological trials results,and the increase in the left hemisphere was significantly higher than that in the right hemisphere;After sham i TBS+real EA,the activation of both hemispheres decreased significantly,which was consistent with the electrophysiological trials results,and the amplitude of the right hemisphere decreased significantly higher than that of the left hemisphere;After real i TBS+sham EA,the activation of the two hemispheres was not significantly different from the baseline,which is consistent with the electrophysiological trials results.The lateralization index（LI）shows:at baseline and real i TBS+sham EA,LI is roughly symmetrical;at real i TBS+real EA,LI is slightly to the left;at sham i TBS+real EA,LI is severely left.The results of resting state f MRI showed no significant or consistent changes in neural activity in the brain regions associated with motor.Conclusion:1)The results of electrophysiological trials showed that after real i TBS+real EA,the excitability of the motor cortex was significantly increased and continued beyond 40 min after the end of the intervention;sham i TBS+real EA significantly inhibited the excitability of the motor cortex,and gradually returned to the pre-intervention level 40 minutes after the end of the intervention;there were no significant changes in cortical excitability after real i TBS+sham EA,sham i TBS+sham EA intervention compared to baseline.2)The results of the task-based f MRI trials were consistent with the results of the electrophysiological trials,and revealed the lateralization of brain activation caused by the different interventions.Resting state f MRI did not show significant changes in neural activity associated with motor-related brain regions.PartⅡ.Preliminary study on the effect of i TBS combined with electroacupuncture on the upper limbs of stroke patients with hemiplegiaObjective:To evaluate the efficacy of i TBS combined with EA in improving upper limb dyskinesia in patients with ischemic stroke by measuring electrophysiological and behavioral indicators.Methods:From November 2018 to March 2019,12 cases of hospitalized patients with upper extremity motor dysfunction after ischemic stroke in the rehabilitation department and acupuncture department of Yueyang Hospital,of which 0 were shed and 0 were excluded.The included patients were randomly assigned to 3 groups（test group:i TBS+EA;control group 1:sham i TBS+EA;control group 2:EA）,4 in each group.Electrophysiological and behavioral indicators were evaluated before treatment（0 weeks）,after treatment（1 week）.Statistical analysis was performed using a two-sample t-test and a paired-sample t-test.Results:There was no significant difference in the simplified Fugl-Meyer upper limb motor function score and RMT between the 3 groups before treatment（P>0.05）.And there were no significant differences in electrophysiological and behavioral parameters between the three groups after 5 days of treatment（P>0.05）.Conclusion:The design of this study did not demonstrate that short-term intervention（5days）with i TBS in combination with EA was superior to EA and sham i TBS+EA in the treatment of upper extremity motor dysfunction in patients with ischemic stroke.It is speculated that it may be mainly related to the treatment time is too short.