Electroacupuncture treatment improves motor function and neurological outcomes after cerebral ischemia/reperfusion injury

Electroacupuncture(EA)has been widely used for functional restoration after stroke.However,its role in post-stroke rehabilitation and the associated regulatory mechanisms remain poorly understood.In this study,we applied EA to the Zusanli(ST36)and Quchi(LI11)acupoints in rats with middle cerebral artery occlusion and reperfusion.We found that EA effectively increased the expression of brain-derived neurotrophic factor and its receptor tyrosine kinase B,synapsin-1,postsynaptic dense protein 95,and microtubule-associated protein 2 in the ischemic penumbra of rats with middle cerebral artery occlusion and reperfusion.Moreover,EA greatly reduced the expression of myelin-related inhibitors Nogo-A and NgR in the ischemic penumbra.Tyrosine kinase B inhibitor ANA-12 weakened the therapeutic effects of EA.These findings suggest that EA can improve neurological function after middle cerebral artery occlusion and reperfusion,possibly through regulating the activity of the brain-derived neurotrophic factor/tyrosine kinase B signal pathway.All procedures and experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine,China(approval No.PZSHUTCM200110002)on January 10,2020.

Brain plasticity after peripheral nerve injury treatment with massage therapy based on resting-state functional magnetic resonance imaging

Massage therapy is an alternative treatment for chronic pain that is potentially related to brain plasticity.However,the underlying mechanism remains unclear.We established a peripheral nerve injury model in rats by unilateral sciatic nerve transection and direct anastomosis.The experimental rats were treated over the gastrocnemius muscle of the affected hindlimb with a customized massage instrument(0.45 N,120 times/min,10 minutes daily,for 4 successive weeks).Resting-state functional magnetic resonance imaging revealed that compared with control rats,the amplitude of low-frequency fluctuations in the sensorimotor cortex contralateral to the affected limb was significantly lower after sciatic nerve transection.However,amplitudes were significantly higher in the massage group than in a sham-massage group.These findings suggest that massage therapy facilitated adaptive change in the somatosensory cortex that led to the recovery of peripheral nerve injury and repair.This study was approved by the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine of China(approval No.201701001)on January 12,2017.

Patterns of cortical reorganization in facial synkinesis:a task functional magnetic resonance imaging study

Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles.This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis,using the task functional magnetic resonance imaging.Facial motor tasks,including blinking and smiling,were performed by 16 patients（aged 30.6 ± 4.5 years,14 females/2 males） and 24 age-and sex-matched healthy controls（aged 29.1 ± 4.2 years,19 females/5 males）.Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls.Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face,than those on the unaffected side.Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area.This study was registered in Chinese Clinical Trial Registry（registration number： Chi CTR1800014630）.

Surface-based map plasticity of brain regions related to sensory motor and pain information processing after osteonecrosis of the femoral head

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical positioning of functional data.The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,20 patients with osteonecrosis of the femoral head(12 males and 8 females,aged 56.80±13.60 years)and 20 healthy controls(9 males and 11 females,aged 54.56±10.23 years)were included in this study.Data of resting-state functional magnetic resonance imaging were collected.The results revealed that compared with healthy controls,compared with the healthy controls,patients with osteonecrosis of the femoral head(ONFH)showed significantly increased surface-based regional homogeneity(Re Ho)in areas distributed mainly in the left dorsolateral prefrontal cortex,frontal eye field,right frontal eye field,and the premotor cortex and decreased surface-based Re Ho in the right primary motor cortex and primary sensory cortex.Regions showing significant differences in surfacebased Re Ho values between the healthy controls and patients with ONFH were defined as the regions of interests.Seed-based functional connectivity was performed to investigate interregional functional synchronization.When the areas with decreased surface-based Re Ho in the frontal eye field and right premotor cortex were used as the regions of interest,compared with the healthy controls,the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex.Compared with healthy controls,patients with ONFH showed significantly decreased cortical thickness in the para-insular area,posterior insular area,anterior superior temporal area,frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens.These findings suggest that hip disorder patients showed cortical plasticity changes,mainly in sensorimotor-and pain-related regions.This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine(approval No.2018-041)on August 1,2018.

Effects of paired associative magnetic stimulation between nerve root and cortex on motor function of lower limbs after spinal cord injury:study protocol for a randomized controlled trial

Classic paired associative stimulation can improve synaptic plasticity,as demonstrated by animal expe riments and human clinical trials in spinal cord injury patients.Paired associative magnetic stimulation(dual-target peripheral and central magnetic stimulation)has been shown to promote neurologic recove ry after stroke.However,it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury.We hypothesize that the curre nt caused by central and peripheral magnetic stimulation will conve rge at the synapse,which will promote synapse function and improve the motor function of the relevant muscles.Therefore,this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials,motor and sensory function of the lower limbs,functional health and activities of daily living,and depression in patients with spinal co rd injury.We will recruit 110 thora cic spinal trauma patients treated in the Department of Spinal Cord Injury,China Rehabilitation Hospital and randomly assign them to expe rimental and control groups in a 1:1 ratio.The trial group(n=55)will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment.The control group(n=55)will be treated with sham stimulation and co nventional rehabilitation treatment.Outcomes will be measured at four time points:baseline and 4,12,and 24 wee ks after the start of inte rvention(active or sham paired associative magnetic stimulation).The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up.Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function sco re,motor evoked potentials,sensory evoked potentials,modified Ashwo rth scale score,Maslach Burnout Invento ry score,and Hamilton Depression Scale score over time.Motor evoked potential latency reflects corticospinal tract transmission time,while amplitude reflects recruitment ability;both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency.Adve rse events will be recorded.Findings from this trial will help to indicate whether paired associative magnetic stimulation(1)promotes recove ry of lower limb sensory and motor function,reduces spasticity,and improves quality of life;(2)promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity;and(3)improves rehabilitation outcome in patients with spinal cord injury.Recruitment for this trial began in April 2021 and is currently ongoing.It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University,China(approval No.YZ2020-018)on May 18,2020.The study protocol was registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044794)on March 27,2021(protocol version 1.0).This trial will be completed in April 2022.

Structural remodeling in related brain regions in patients with facial synkinesis

Facial synkinesis is a troublesome sequelae of facial nerve malfunction.It is difficult to recover from synkinesis,despite improved surgical techniques for isolating the peripheral facial nerve branches.Furthermore,it remains unclear whether long-term dysfunction of motor control can lead to irreversible plasticity-induced structural brain changes.This case-control study thus investigated the structural brain alterations associated with facial synkinesis.The study was conducted at Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China.Twenty patients with facial synkinesis(2 male and 18 female,aged 33.35±6.97 years)and 19 healthy volunteers(2 male and 17 female,aged 33.21±6.75 years)underwent magnetic resonance imaging,and voxel-based and surface-based morphometry techniques were used to analyze data.There was no significant difference in brain volume between patients with facial synkinesis and healthy volunteers.Patients with facial synkinesis exhibited a significantly reduced cortical thickness in the contralateral superior and inferior temporal gyri and a reduced sulcal depth of the ipsilateral precuneus compared with healthy volunteers.In addition,sulcal depth of the ipsilateral precuneus was negatively correlated with the severity of depression.These findings suggest that there is a structural remodeling of gray matter in patients with facial synkinesis after facial nerve malfunction.This study was approved by the Ethics Review Committee of the Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,China(approval No.2017-365-T267)on September 13,2017,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR1800014630)on January 25,2018.

Altered intra- and inter-network brain functional connectivity in upper-limb amputees revealed through independent component analysis

Although cerebral neuroplasticity following amputation has been observed, little is understood about how network-level functional reorganization occurs in the brain following upper-limb amputation. The objective of this study was to analyze alterations in brain network functional connectivity(FC) in upper-limb amputees(ULAs). This observational study included 40 ULAs and 40 healthy control subjects;all participants underwent resting-state functional magnetic resonance imaging. Changes in intra-and inter-network FC in ULAs were quantified using independent component analysis and brain network FC analysis. We also analyzed the correlation between FC and clinical manifestations, such as pain. We identified 11 independent components using independent component analysis from all subjects. In ULAs, intra-network FC was decreased in the left precuneus(precuneus gyrus) within the dorsal attention network and left precentral(precentral gyrus) within the auditory network;but increased in the left Parietal_Inf(inferior parietal, but supramarginal and angular gyri) within the ventral sensorimotor network, right Cerebelum_Crus2(crus Ⅱ of cerebellum) and left Temporal_Mid(middle temporal gyrus) within the ventral attention network, and left Rolandic_Oper(rolandic operculum) within the auditory network. ULAs also showed decreased inter-network FCs between the dorsal sensorimotor network and ventral sensorimotor network, the dorsal sensorimotor network and right frontoparietal network, and the dorsal sensorimotor network and dorsal attention network. Correlation analyses revealed negative correlations between inter-network FC changes and residual limb pain and phantom limb pain scores, but positive correlations between inter-network FC changes and daily activity hours of stump limb. These results show that post-amputation plasticity in ULAs is not restricted to local remapping;rather, it also occurs at a network level across several cortical regions. This observation provides additional insights into the plasticity of brain networks after upper-limb amputation, and could contribute to identification of the mechanisms underlying post-amputation pain.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury:a resting-state functional MRI study

Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

Although some patients have successful peripheral nerve regeneration,a poor recovery of hand function often occurs after peripheral nerve injury.It is believed that the capability of brain plasticity is crucial for the recovery of hand function.The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury.In this study,we explored the activation mode of the supplementary motor area during a motor imagery task.We investigated the plasticity of the central nervous system after brachial plexus injury,using the motor imagery task.Results from functional magnetic resonance imaging showed that after brachial plexus injury,the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas.This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task,thereby impacting brain remodeling.Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing,initiating and executing certain movements,which may be partly responsible for the unsatisfactory clinical recovery of hand function.