Multimodal Functional Magnetic Resonance Study Of Repeated Transcranial Magnetic Stimulation For Acute Ischemic Stroke

Part 1 Cerebral Functional Changes of Ischemic Stroke Patients in the Acute StageOBJECTIVE To investigate functional connectivity(FC)changes after stroke through the method of resting-state functional magnetic resonance imaging(rs-fMRI)in the early acute stage,thus providing clues for stroke rehabilitation.METHODS Rs-fMRI of 23 patients with first-onset acute ischemic stroke and 40 gender-and age-matched healthy volunteers was achieved.The infarctions were all unilateral and within areas supplied by the middle cerebral artery.The ipsilesional primary motor cortex(Ml)was selected as the region of interest(ROI).As to the healthy controls,the right Ml was chosen as the ROI.Correlation analysis between time course of the ipsilesional Ml and that of every voxel in the whole brain was computed for FC maps.A two-sample t test was calculated to investigate difference between the stroke patients and the healthy volunteers.RESULTS Compared with the healthy volunteers,the stroke patients showed decreased FC between ipsilesional M1 and contralesional Ml,postcentral gyrus,paracentral lobule,middle frontal gyrus,supplementary motor area,pars triangularis,calcarine,middle and superior occipital gyrus,bilateral cerebellum,ipsilesional fusiform gyrus,precentral gyrus and postcentral gyrus.Increased FC was found between ipsilesional Ml and ipsilesional superior and middle temporal gyrus,middle and inferior frontal gyrus,angular gyrus and contralesional precentral gyrus.CONCLUSIONS Rs-fMRI could well depict cerebral functional changes after stroke.There is a decrease in the interhemispheric connection of motor-related brain regions of stroke patients with motor dysfunction,and the interaction between primary motor cortex and cerebellum declines after stroke.Display of alterations in the resting-state functional connectivity could provide us with clues of individualized treatment plans for stroke patients in the next step.Part 2 Effectiveness and Mechanism of Repetitive Transcranial Magnetic Stimulation(rTMS)in Acute Ischemic Stroke Patients Based on Multimodal Functional Magnetic Resonance ImagingOBJECTIVE To evaluate the effectiveness of rTMS on motor rehabilitation after stroke using a longitudinal,prospective and randomized study,and to explore the central mechanism of rTMS in motor recovery after ischemic stroke through multimodal functional magnetic resonance imaging.METHODS Patients with acute ischemic stroke and dyskinesia were randomized into a real rTMS treatment group and a sham rTMS group respectively.The real rTMS treatment group received a 10-day high frequency and high intensity rTMS applied over the ipsilesional M1 while a sham rTMS treatment with the same parameters was carried out on the sham group.Clinical assessment was evaluated by a professional neurologist pre-and post-real/sham rTMS and at 1 month,3 months,6 months,and 1 year after stroke onset.The scores included the National Institutes of Health Stroke Scale(NIHSS),Barthel Index(BI),Fugl-Meyer Assessment(FMA)of the upper and lower limb,modified Rank Score(mRS),and the resting motor threshold(RMT)of the hemiplegic limb.Besides,Multimodal functional magnetic resonance imaging,including rs-fMRI and diffiision tensor imaging(DTI),was achieved from each patient before and after real/sham rTMS.Correlation between the time course of the ipsilesional Ml and that of every voxel within the brain was analyzed to achieve a cerebral FC map.The contrast between the FC maps post-and pre-rTMS treatment was then calculated for each patient.The achieved differential contrast images were then used for a two-sample t-test to compare the connectivity changes between the rTMS treatment group and the sham group.As to the DTI data,voxel-based analysis of the fractional anisotropy(FA)was carried out before and after the real/sham rTMS respectively to compare the difference between the two groups.RESULTS(1)At baseline,no significant difference was found between the real rTMS treatment group and the sham group for motor functional scores.On the second day after real/sham rTMS treatment,there was no significant difference of clinical scores between the two groups.But score improvements differed.The NIHSS,BI and FMA of the upper limb changed more significantly in the real rTMS treatment group than in the sham group.In addition,similar results were obtained at 1 month.However,at 3 months,6 months,and 1 year after onset,no significant differences in improvement were observed between the two groups,except for the upper limb's FMA score improvement(2)Seven patients in the real rTMS treatment group and five patients from the sham rTMS group received rs-fMRI scans at the time of enrollment and one month after onset.Compared with the sham,the rTMS treatment group achieved increased FC between ipsilesional Ml and contralesional M1,supplementary motor area,bilateral thalamus,and contralesional postcentral gyrus.Decreased FC was found between ipsilesional Ml and ipsilesional M1,postcentral gyrus,inferior and middle frontal gyrus.(3)Six patients in the real rTMS treatment group and six patients the sham rTMS group received DTI scans at the time of enrollment and one month after onset.Before the rTMS,there is no significant difference in FA between the two groups.Differently,after the treatment,the rTMS group showed increased FA in the contralesional corticospinal tract,the pontine crossing tract,the middle cerebellar peduncle,the contralesional superior cerebellar peduncle,the contralesional medial lemniscus,and the ipsilesional inferior cerebellar peduncle.These fasciculi comprise the cortex-pontine-cerebellum-cortex loop.Increased FA was also found in the body of corpus callosum and the contralesional cingulum of the treatment group compared with the sham.The contralesional posterior thalamic radiation and corona radiate had decreased FA after rTMS treatment.CONCLUSIONS RTMS treatment could facilitate functional recovery in patients with acute ischemic stroke,with its main effectiveness lasts until one month after onset.The therapeutic efficacy of rTMS on upper limb motor function could even continue to one year after onset.Through the method of multimodal functional magnetic resonance imaging,our study displayed the brain reorganization after rTMS in vivo and demonstrated that the rTMS promotes motor recovery mainly through strengthening the positive role of contralesional mirror regions,not only functionally but also structurally.