A Multi-modal FMRI Study On The Mechanism Of Repetitive Transcranial Magnetic Stimulation Promoting Motor Recovery In Stroke Patients

Part 1 Aberrances of cortex excitability and connectivity underlying motor deficit in ischemic stroke patients Purpose: This study aimed to evaluate the motor cortical excitability and connectivity underlying the neural mechanism of motor deficit in acute stroke by the combination of functional magnetic resonance imaging(fMRI)and electrophysiological measures.Methods: Twenty-five patients with motor deficit after acute ischemic stroke were involved.General-linear-model and dynamic causal model analyses were applied to fMRI data for detecting motor-related activation and effective connectivity of the motor cortices.Motor cortical excitability was determined as resting motor threshold(RMT)of motor evoked potential detected by transcranial magnetic stimulation(TMS).fMRI results were correlated to cortical excitability and upper extremity Fugl-Meyer Assessment scores,respectively.Results: Greater fMRI activation likelihood and motor cortical excitability in the ipsilesional primary motor area(M1)region were associated with better motor performance.During hand movements,the inhibitory connectivity from the contralesional to the ipsilesional M1 were correlated with the degree of motor impairment.Furthermore,ipsilesional motor cortex excitability was correlated with an enhancement of promoting connectivity in ipsilesional M1 or a reduction of interhemispheric inhibition in contralesional M1.Conclusions: The study suggested that a dysfunction of the ipsilesional M1 and abnormal interhemispheric interactions might underlie the motor disability in acute ischemic stroke.Modifying the excitability of motor cortex and correcting the abnormal motor network connectivity associated with the motor deficit might be the therapeutic target in early neurorehabilitation for stroke patients.Part 2 Early functional MRI activation predicts motor outcome after ischemic stroke:a longitudinal,multimodal study Purpose: An accurate prediction of motor outcome after stroke is urgently required to provide early individualized neurorehabilitation.This study aimed to identify the added value of early neuroimaging measures and the optimal approaches for predicting motor outcome after stroke.Methods: This prospective study involved 34 first-ever ischemic stroke patients(time since stroke: 1–16 days)with upper limb impairment.All patients underwent baseline multimodal assessments that included clinical(age,motor impairment),neurophysiological(motor-evoked potentials,MEP)and neuroimaging(diffusion tensor imaging and motor task-based f MRI)measures,and also underwent reassessment 3 months after stroke.Multivariate linear regression analysis was used to predict the motor scores(Fugl-Meyer assessment,FMA)at 3 months post-stroke.Results: With bivariate analysis,better motor outcome significantly correlated with(1)less initial motor impairment and disability,(2)less corticospinal tract injury,(3)the initial presence of MEPs,(4)stronger baseline motor f MRI activations.In multivariate analysis,incorporating neuroimaging data improved the predictive accuracy relative to only clinical and neurophysiological assessments.Baseline f MRI activation in SMA was an independent predictor of motor outcome after stroke.Conclusion: A multimodal model incorporating f MRI and clinical measures best predicted the motor outcome following stroke.f MRI measures obtained early after stroke provided independent prediction of long-term motor outcome.Part 3 Effects of repetitive transcranial magnetic stimulation over primary motor cortex on motor function and neural activity in early stage of post-stroke patients Purpose: This randomized,sham-controlled,double-blind study was to compare the effects of high-frequency versus low-frequency r TMS on motor recovery and neural activity during the early phase of stroke.Methods: Sixty ischemic stroke patients were randomly allocated to receive five daily sessions of 10-Hz ipsilesional r TMS,1-Hz contralesional r TMS or sham r TMS in addition to standard physical therapy.Behavioral testing scores,cortical excitability and motor task-related f MRI measures were assessed at baseline,after the intervention and at3-month follow-up.Results : Following the r TMS treatment,the real groups showed greater motor improvements than the sham group.Compared with the sham group,10-Hz r TMS group significantly increased the cortical excitability and neural activity in the ipsilesional motor area,1Hz r TMS significantly decreased the overactivity of cortical excitability and neural activity in the contralesional motor area.Both cortical excitability and neural activity correlated with the motor function at post-intervention.However,we did not found the significant change for motor function,cortical excitability and neural activity among three r TMS groups.Conclution: High-frequency or low-frequency r TMS coupling with standard physiotherapy promoted motor recovery through modulationg different motor cortical activity patterns in the acute and subacute phase after stroke.Part 4 Early functional reorganization of the motor network after repetitive transcranial magnetic stimulation impoves motor recovery in ischemic stroke Purpose: To test the effects of high-frequency and low-frequency r TMS on functional reorganization of the cortical motor network and motor recovery during the early phase of stroke.Methods: Forty-six first-ever stroke patients with upper limb motor deficits were randomly divided into three groups,and received the five daily sessions of 10-Hz ipsilesional r TMS,1-Hz contralesional r TMS or sham r TMS in addition to standard physical therapy.All patients underwent both motor function and resting-state f MRI assessement 24 hours prior to the first stimulation(baseline)and 24 hours after the last stimulation(post-intervention)and at 3-month follow-up.Results: The real r TMS groups showed greater motor improvements than the sham group after intervention.Compared with the sham group,the real r TMS groups featured increased intra-and interhemisphere functional connectivity(FC)of the motor network from baseline to post-intervention,which correlated with the motor recovery.At 3-month follow-up,we found there was significant functional connectivity change in low-frequency r TMS group.Conclusion: The effects of adding high-frequency or low-frequency r TMS to standard motor training in motor recovery for early stroke patients by modulating the cortical motor network reorganization.