The Clinical Effect And Mechanism Of Coupling Inhibitory And Excitability RTMS On Motor Recovery In Acute Cerebral Infarction

BACKGROUND:Recently,With the development of brain science and technology,studies have shown that rTMS has broad application prospects in improving poststroke motor dysfunction.However,current studies mainly focus on the chronic phase,yet few concentra te on the treatment of rTMS in the acute phase of stroke.Based on previous studies of neuroplasticity,the first 3 months after stroke are the most critical period for nerve repair.Therefore,this study focuses on early stroke of rTMS neurorehabilitation.Previous rTMS research results have confirmed that high-frequency stimulation(>1Hz)can excite neurons,while low-frequency stimulation(≤1 Hz)can inhibit neurons.The clinical application of rTMS technology helps to improve patients’limb motor function.Based on the above research results,we infer that coupling inhibitory and excitability rTMS therapy may be one of the more effective treatment methods.Therefore,the purpose of this study is to further explore the clinical effect and mechanism of this kind of coupling inhibitory and excitability rTMS technology,aiming to provide a new treatment plan for the clinical application of rTMS.In addition,with the development of magnetic resonance imaging(MRI)technology in recent years,the combined application of functional magnetic resonance and spectroscopy technology can help evaluate the effect of rTMS treatment objectively and further explore the mechanism of recovery of nerve damage after stroke,which provides evidence for the choice of effective rehabilitation techniques and for revealing the plasticity mechanism of sports injury and recovery after stroke.Based on the above research background,This research aimed to introduce the clinical and multi-modal MRI evaluation methods to observe the clinical efficacy of rTMS in improving motor function after acute stroke,and to further discuss its active mechanism.Part 1 Effects of coupling inhibitory and excitability repetitive transcranial magnetic stimulation on motor recovery in patients following acute cerebral infarctionBACKGROUND:The patients treatment suffering from motor recovery following stroke using single-course inhibitory or excitatory repetitive transcranial magnetic stimulation(rTMS)modulation alone can be beneficial for recovery.However,the impacts of explicit results on the coupling of various rTMS protocols on motor recovery in patients following acute cerebral infarction remain unexplored.OBJECTIVE:The current study aims to design a sham-controlled randomized report to explore the capability of consecutive suppressive-facilitatory rTMS method to increase the motor results following acute stroke.METHODS:The subjects of this part of the study are ischemic stroke patients suffering from motor disorder were randomly assigned to four groups and obtain 4 weeks sessions of rTMS intervention(1)group A:1Hz over the contralesional primary motor cortex(M1)and next 10Hz over the ipsilesional M1;(2)group B:contralesional sham stimulation and next ipsilesional real 10Hz;(3)group C:contralesional real 1 Hz rTMS and next ipsilesional sham stimulation;or(4)group D:bilateral sham-control procedures.At 24 hours before and after the intervention,we obtained cortical excitability data from study subjects.At baseline,after treatment and 3 months follow up,we additionally evaluated patients with the clinical assessments.In the end,100 patients completed all assessments and follow-ups.RESULTS:At post,group A showed greater motor improvements in FMA,FMA-UL,NIHSS,ADL and mRS values than group B,group C and group D,that were continued for at least 3 months after the completion of the treatment time.Specifically,it is shown in the cortical excitability study that the motor-evoked potential(MEP)amplitude and resting motor threshold(rMT)more significantly improved in group A than other groups.The improvement in motor function and change in motor cortex excitability exhibit a significant correlation in the affected hemisphere.The combined 1Hz and 10Hz stimulation treatment showed a synergistic effect.CONCLUSIONS:Inhibitory rTMS and coupling facilitatory produced extra satisfactory results in facilitating the motor’s recovery in the subacute and acute phase following stroke compared to that acquired from alone single-course modulation mode.Part 2 The Effects of coupling inhibitory and facilitatory rTMS on Motor Networks Functional Connectivity in Acute StrokeBACKGROUND:Neural plasticity is a major factor driving cortical reorganization after stroke.OBJECTIVE:The objective of the present study was to evaluate the changes of cortical motor network connection before and after treatment with coupling inhibitory and facilitatory rTMS used resting-state fMRI(rs-fMRI)and its correlation with recovery of motor function,to further explore the neural mechanism of this therapy in promoting the recovery of motor functions.METHODS:The subjects were randomly divided into four groups:(1)Group A was coupling inhibitory and facilitatory rTMS group(1Hz over the contralesional primary motor cortex(M1)+10Hz over the ipsilesional M1);(2)Group B(contralesional sham stimulation+ipsilesional real 10Hz);(3)Group C(contralesional real 1 Hz rTMS+ipsilesional sham stimulation);Or(4)group D(bilateral sham stimulation),each group received treatment for 4 weeks.At 24 hours before and after the intervention,we obtained resting-state functional magnetic resonance(rs-fMRI)data from study subjects.At baseline,after treatment and 3 months follow up,we additionally evaluated patients with the clinical assessments.Finally,63 patients with acute stroke were included in the statistical analysis.RESULTS:At post,group A showed greater motor improvements in FMA,FMA-UL,NIHSS,ADL and mRS values than group B,group C and group D,that were continued for at least 3 months after the completion of the treatment time.The results of functional connectivity(FC)assessment showed that after treatment the intra-and inter-hemispheric cortical motor network FC was significant enhanced in the rTMS group(group A,B,and C)compared with the sham stimulation group(group D).In addition,compared with group B and group C,group A significantly enhanced the FC in the affected side(superior parietal gyrus-precentral gyrus and superior parietal gyrus-putamen)and the unimpaired side(precentral gyrus-postcentral gyrus).And the last,the enhancement of FC with significant differences between groups was significantly related to the improvement of motor functions.CONCLUSIONS:In the acute stage of ischemic stroke,coupling inhibitory and facilitatory rTMS is superior to single-course modulation alone,and can improve motor dysfunction more significantly by changing the intra-and inter-hemispheric motor network FC.Part 3 Magnetic Resonance Spectra Research on the Motor Cortex GABA Levels of Cerebral Stroke PatientsBACKGROUND:y-Aminobutyric acid(GABA)plays a key role in motor learning.Up to now,few researches have been done on the GABA levels in the motor cortexes of acute stroke patients.OBJECTIVE:With acute stroke patients as research subjects,we monitored GABA content of primary motor cortex(M1 area)by magnetic resonance spectroscopy(MRS).METHODS:The cohort included 20 patients,each experiencing stroke within 2 weeks of symptom onset.Twenty age-matched healthy subjects were also recruited as controls.All participants underwent GABA level measuring in M1 area of bilateral hemisphere.Because GABA,macromolecules,and homocarnosine jointly contribute to MEscher-Garwood Point RESolved Spectroscopy(MEGA-PRESS)signals,the designation GABA+(rather than GABA)was applied.RESULTS:Baseline GABA/creatine(Cr)ratios proved significantly lower in patients with strokes than in control subjects(P<0.05).In the setting of acute stroke,GABA/Cr ratios of primary motor cortex fell significantly below levels found in healthy subjects.CONCLUSIONS:this part finds out that MRS can be used to measure the GABA levels in the M1 area of acute stroke patients.In the future,it is clinically practical to use the GABAlevels as the target for clinical interventions.Part 4 Effect of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation on GABA level in motor cortex among patients with acute strokeBACKGROUND:The therapeutic mechanism of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation(rTMS)for treatment motor dysfunction following stroke may involve y-aminobutyric acid(GABA)levels.OBJECTIVE:We used proton magnetic resonance spectroscopy(MRS)to assess changes in GABA levels during 4 weeks of rTMS in bilateral motor cortex(M1).METHODS:The patients with acute ischemic stroke included in this study were randomly assigned to obtain 4 weeks sessions of(1)real stimulation group:1Hz over the contralesional M1 and next10-Hz over the ipsilesional primary motor cortex(M1);(2)sham stimulation group:bilateral sham-control procedures.GABA levels were assessed at baseline and following rTMS.At 24 hours before and after the intervention,we obtained GABA data from study subjects.At baseline,after treatment and 3 months follow up,we additionally evaluated patients with the clinical assessments.Finally,statistical analysis was performed on the evaluation results of 44 patients.RESULTS:At post,real stimulation group showed greater motor improvements in FMA,FMA-UL,NIHSS,ADL,mRS and MMSE values than sham stimulation group,that were continued for at least 3 months after the completion of the treatment time.Following 4 weeks of rTMS,GABA levels(in ipsilesional M1)decline in real stimulation group compared to sham stimulation one.Futhermore,the extent of improvement on FMA correlated significantly with the magnitude of GABA:Cr changes,with decreases in GABA:Cr ratio being associated with better improvements in motor function.CONCLUSIONS:After intervention,the level of patient GABA decreases was significantly correlated with the extent of improvement in motor performance.Coupling inhibitory and facilitatory rTMS can improve motor function by regulating GABA level.Therefore,this intervention is worthy of further promotion and application in clinic.