A Multimodal Magnetic Resonance Imaging Study On The Mechanism Of Acupuncture Treatment For Hemiplegia Caused By Stroke Based On Brain Connectivit

Objective:In this study,multimodal magnetic resonance imaging was used to acquire functional and structural brain data,and dynamic causal modelling and probabilistic white matter fibre tracking techniques were applied to investigate the effective connectivity patterns of the motor cortex connectivity group and the changes in brain white matter integrity in stroke patients with hemiplegia from the perspective of brain connectivity,and to investigate the central effect mechanism and the specificity of the acupuncture point effect on the regulation of brain connectivity by the "hand-foot-twelve-needle" treatment.Methods:Study 1:Patients with stroke hemiplegia with unilateral motor pathway injury were studied,54 patients within 2 months of onset were included,and 29 healthy controls were matched according to gender and age for comparative analysis.A dynamic causal modelling was applied to calculate the effective connections in the bilateral motor cortex connection groups,and a probabilistic white matter fibre tracking technique was applied to analyze the changes in the structural connections in the white matter of the brain to quantify the structural and functional changes in patients with stroke hemiplegia and to analyze the structural and functional changes in patients with stroke hemiplegia by combining the Fugl-Meyer Motor Function Scale（FMA）,the National Institutes of Health Stroke Scale（NIHSS）and other clinical scales.The correlation between brain changes and the degree of motor function and neurological deficits in stroke patients with hemiplegia was analyzed.Study 2:Patients with stroke hemiplegia with unilateral motor pathway injury were studied,and the treatment protocol of "hand-foot-twelve-needle" was used for acupuncture treatment,with a 2:1 ratio of real acupuncture points to sham acupuncture points.36 patients in the real acupuncture point group and 18 patients in the sham acupuncture point group were included in the study,and the clinical indexes such as FMA and NIHSS scores of the two groups were compared and analyzed before and after treatment.To verify the efficacy of the treatment of stroke hemiplegia with "hand-foot-twelve-needle".The functional and structural brain imaging was completed twice before and after the acupuncture treatment course,and the functional connectivity of the bilateral motor cortex connectivity group was analyzed before and after the treatment by applying the resting-state functional connectivity analysis method.The dynamic causal modelling was applied to analyze and calculate the changes in effective connectivity of the bilateral motor cortex connectivity group before and after the treatment,and the probabilistic white matter fibre tracking technique was applied to analyze the changes in the structural integrity of cerebral white matter before and after the treatment.The changes in the structural integrity of the white matter of the brain before and after treatment were analyzed by applying the probabilistic white matter fibre tracking technique,and the central specificity of the acupuncture effect and the mechanism of the central effect of acupuncture in the treatment of stroke hemiplegia were investigated by comparing two groups of patients with real and fake acupuncture points.Results:Study 1:1 Dynamic causal modelling analysisThe dynamic causal modelling was used to obtain the two-way connections between six brain areas in the motor cortex connectivity group,namely,bilateral primary motor area（M1）,supplementary motor area（SMA）,and premotor cortex（PMC）,with a total of 30 pairs of effective connectivity values（effective connectivity,EC）.The mean or median of the 30 pairs of EC values was compared with 0.M1→right M1,left SMA→left PMC,right PMC,right SMA,and right M1→left M1 were activated in healthy human subjects control group;left M1→left SMA,right SMA,left PMC→left SMA,right SMA,right M1→left SMA,right SMA,right PMC→left SMA was the inhibiting effect.In the patient group,the healthy（left）SMA→healthy M1,healthy PMC,affected（right）SMA,affected M1→healthy PMC,affected SMA→healthy SMA was the activating effect;healthy M1→healthy SMA,healthy PMC→healthy SMA,affected M1,affected SMA,affected PM→healthy SMA,affected SMA,affected M1→affected SMA was the inhibiting effect.Comparing the effective connection strengths of healthy individuals with those of stroke hemiplegia,it was found that the effective connection values of the patients’ healthy SMA→healthy M1 and affected SMA→healthy SMA were increased and those of healthy M1→affected M1,healthy PMC→affected M1,and healthy SMA→affected M1 were decreased compared with those of healthy individuals.Notably,unlike healthy subjects,the mode of action of healthy SMA→healthy M1,healthy PMC→affected PMC,and affected M1→affected PMC changed from inhibition to activation in patients.A total of 30 pairs of valid connectivity values between six brain regions in the motor cortex connectivity group of the patient group were correlated with the FMA of upper limb（FMA-U）,FMA of lower limb（FMA-L）,FMA total score（FMA total score）and the NIHSS scores of the four clinical scales.The FMA total score was positively correlated with the effective connection between M1 on the healthy side and M1 on the affected side and PMC on the healthy side and M1 on the affected side.The FMA-U was positively correlated with the effective connection between M1 on the healthy side and M1 on the affected side and PMC on the healthy side and M1 on the affected side.The FMA-L score was positively correlated with the effective connection between M1 on the healthy side and M1 on the affected side,and the NIHSS score was negatively correlated with the effective connection between M1 on the healthy side and M1 on the affected side.2 Probabilistic fibre tracking analysisProbabilistic fibre tracking analysis was performed using the PANDA toolkit,which allows subjects to divide the white matter of the brain into 50 brain regions and obtain the corresponding FA values based on its built-in rICBM_DTI₈1_WMPM_FMRIB58 white matter atlas.Patient’s mid-cerebellar peduncle,transverse pontine tract,corpus callosum knee,corpus callosum body,corpus callosum pressure,vault（column,body）,affected（right）corticospinal tract,healthy（left）corticospinal tract,healthy medial thalamus,affected inferior cerebellar peduncle,healthy inferior cerebellar peduncle,affected superior cerebellar peduncle,healthy superior cerebellar peduncle,affected cerebellar peduncle,healthy cerebellar peduncle,affected anterior limb of internal capsule,healthy anterior limb of internal capsule,affected posterior limb of internal capsule,healthy posterior limb of the internal capsule,posterior bean of the affected internal capsule,anterior corona radiata of the affected side,anterior corona radiata of the healthy side,superior corona radiata of the affected side,superior corona radiata of the healthy side,posterior corona radiata of the affected side,posterior corona radiata of the healthy side,posterior corona radiata of the affected side,posterior corona radiata of the healthy side,sagittal layer of the affected side,external capsule of the affected side,external capsule of the healthy side,cingulate gyrus of the affected side,cingulate gyrus of the healthy side,cingulate gyrus of the affected side,cingulate gyrus of the healthy side,cingulate gyrus of the healthy side,cingulate gyrus of the healthy side The FA values of the affected dome/terminal stripe,affected dome/terminal stripe,affected superior longitudinal fasciculus,healthy superior longitudinal fasciculus,affected superior frontal occipital fasciculus,healthy superior frontal occipital fasciculus,affected inferior frontal occipital fasciculus,healthy hook fasciculus,affected chordae,and healthy chordae were lower than those of healthy subjects.According to the JHU_Tract atlas,the white matter of the subject’s brain was divided into 20 major fibre tracts,and the mean FA values of each voxel on each fibre tract were obtained.The FA values of the patient’s bilateral thalamic radial tract,bilateral corticospinal tract,bilateral cingulate tract cingulate gyrus,corpus callosum major clamp,corpus callosum minor clamp,bilateral inferior frontal occipital tract,bilateral inferior longitudinal tract,affected superior longitudinal tract,bilateral hook tract,and affected arch tract were lower than those of healthy subjects.The FA values of the 50 brain regions segmented by patients according to the rICBM_DTI₈1_WMPM_FMRIB58 atlas were correlated with four clinical scale scores,including the FMA-U score,FMA-L score,FMA total score and the NIHSS score.The FMA total score was positively correlated with the FA value of the affected posterior internal capsule limb;the FMA upper limb score was positively correlated with the FA value of the affected posterior internal capsule limb and negatively correlated with the FA value of the healthy posterior radiological crown.The FMA-L score was positively correlated with the FA value of the affected posterior internal capsule limb,the FA value of the affected posterior bean of the internal capsule,the FA value of the affected posterior radiological crown,the FA value of the affected sagittal layer,and the FA value of the affected hook bundle.The FA values of 20 fibre tracts segmented by the Johns Hopkins White Matter Fiber Tract Atlas were correlated with the scores of four clinical scales,and the results showed that the NIHSS scores of patients with hemiparesis were positively correlated with the FA values of the corticospinal tract on the healthy side.The FMA total score was positively correlated with the FA values of the corticospinal tract on the affected side.The FMA-L score was positively correlated with the FA values of the corticospinal tract on the affected side and the FA values of the hook tract on the affected side.The FMA lower limb score was positively correlated with the FA value of the affected corticospinal tract and the FA value of the affected hook tract.Study 2:1 Functional brain connectivity analysisThe FC values of M1 on the healthy side-M1 on the affected side and SMA on the affected side-PMC on the healthy side of the patients in the true acupuncture group were higher than those before acupuncture treatment.There was no statistical difference in FC values between brain regions before and after acupuncture treatment in the patients in the sham acupuncture group.There was no statistical difference in the 15 groups of functional connectivity between the two groups of patients after treatment.2 Dynamic causal modelling analysisAfter treatment,patients in the sham acupuncture point group had an activating effect of affected SMA→healthy SMA and healthy SMA→affected PMC and an inhibiting effect of healthy SMA→affected M1.The patients in the true acupuncture point group had the activating effect of affected side M1→healthy side M1,affected side SMA→healthy side SMA,affected side SMA→affected side PMC,and healthy side SMA→affected side SMA,and the inhibitory effect of healthy side PMC→healthy side SMA,affected side M1→healthy side SMA,affected side PMC→healthy side SMA,healthy side PMC→affected side SMA,affected side M1 affected side SMA,and affected side PMC→affected side SMA.The EC values of healthy side PMC→affected side SMA and affected side M1→healthy side M1 after acupuncture in the true acupuncture group were higher than before acupuncture treatment.The EC values of affected side M1→healthy side PMC and healthy side PMC→affected side M1 after acupuncture treatment in the sham acupuncture group were lower than before treatment,and the EC values of healthy side PMC→affected side M1 were higher than before treatment.There was no statistical difference in the 30 pairs of effective connection values between the two groups of patients after treatment.3 Probabilistic fibre tracking analysisThe FA values of the affected corticospinal tracts after acupuncture in 50 brain regions segmented based on the rICBM_DTI₈1_WMPM_FMRIB58 white matter atlas were lower in patients in the true acupuncture group than before treatment.The FA values of the affected corticospinal tracts,the affected cerebral peduncle,the healthy cingulate tract cingulate gyrus,and the healthy supra frontal occipital tract were lower in patients in the sham acupuncture group than before treatment.The FA values of the 50 brain regions in the two groups were reduced compared with those before treatment.There was no statistical difference between the two groups based on the FA values of 20 fibre tracts segmented from Johns Hopkins white matter fibre tracts before and after the treatment and between the groups.Conclusions:1 The alteration of the effective connectivity pattern of the motor cortex connectivity group in patients with stroke hemiplegia is characterized by reduced connectivity between the bilateral hemispheres of the brain,increased activity in the healthy hemisphere and inhibition in the affected hemisphere,and the white matter damage in the brain is characterized by a bilateral and extensive nature.2 "hand-foot-twelve-needle" can improve the motor function and neurological deficits of the limbs in patients with stroke hemiplegia,regulate the functional connection and effective connection of bilateral M1,PMC on the healthy side and SMA on the affected side,and control or even reduce the development of brain white matter injury to a certain extent.3 The sham acupuncture treatment can also play a role in regulating the effective connections of the motor cortical junction group,but the scope of action and the regulation of key sites are inferior to those of the real acupuncture treatment,and the damage to the white matter of the brain is more extensive after the treatment,so the "hand-foot-twelve-needle"treatment has acupoint specificity.