Effect of Paired Associative Stimulation on Motor Cortex Excitability in Rats

Paired associative stimulation (PAS),combining transcranial magnetic stimulation (TMS) with electrical peripheral nerve stimulation (PNS) in pairs with an optimal interstimulus interval (ISI)in between,has been shown to influence the excitability of the motor cortex (MC)in humans.However,the underlying mechanisms remain unclear.This study was designed to explore an optimal protocol of PAS,which can modulate the excitability of MC in rats,and to investigate the underlying mechanisms. The resting motor thresholds (RMTs) of TMS-elicited motor evoked potentials (MEPs) recorded from the gastrocnemius muscle and the latency of P1 component of somatosensory evoked potentials (SEPs) induced by electrical tibial nerve stimulation were determined in male Sprague-Dawley rats (n=10).Sixty rats were then randomly divided into 3 groups:a PAS group (further divided into 10 subgroups at various ISIs calculated by using the latency of P1,n=5,respectively),a TMS (only)group (n=5)and a PNS (only)group (n=5).Ninety repetitions of PAS,TMS and PNS were administered to the rats in the 3 groups,respectively,at the frequency of 0.05 Hz and the intensity of TMS at 120% RMT and that of PNS at 6 mA.RMTs and motor evoked potentials'amplitude (MEPamp)were recorded before and immediately after the interventions.It was found that the MEPamp significantly decreased after PAS at ISI of 5 ms (P<0.05),while the MEPamp significantly increased after PAS at ISI of 15ms,as compared with those before the intervention (P<0.05).However,the RMT did not change significantly after PAS at ISI of 5 ms or 15 ms (P>0.05).PAS at other ISis as well as the sole use of TMS and PNS induced no remarkable changes in MEPamp and RMT.In conclusion,PAS can influence motor cortex excitability in rats.Neither TMS alone nor PNS alone shows significant effect.

Paired associated magnetic stimulation promotes neural repair in the rat middle cerebral artery occlusion model of stroke

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment.However,the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear.In this study,rats were randomly divided into middle cerebral occlusion model(MCAO)and paired associated magnetic stimulation(PAMS)groups.The MCAO rat model was produced by middle cerebral artery embolization.The PAMS group received PAMS on days 3 to 20 post MCAO.The MCAO group received sham stimulation,three times every week.Within 18 days after ischemia,rats were subjected to behavioral experiments—the foot-fault test,the balance beam walking test,and the ladder walking test.Balance ability was improved on days 15 and 17,and the footfault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group.Western blot assay showed that the expression levels of brain derived neurotrophic factor,glutamate receptor 2/3,postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21.Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere,but decreased in the contralateral hemisphere on day 20.By finite element simulation,the electric field distribution showed a higher intensity,of approximately 0.4 A/m^2,in the ischemic cortex compared with the contralateral cortex in the template.Together,our findings show that PAMS upregulates neuroplasticity-related proteins,increases regional brain activity,and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model.The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University,China(approval No.201802173 S)on March 3,2018.

Paired associative stimulation improves synaptic plasticity and functional outcomes after cerebral ischemia

Paired associative stimulation is a relatively new non-invasive brain stimulation technique that combines transcranial magnetic stimulation and peripheral nerve stimulation. The effects of paired associative stimulation on the excitability of the cerebral cortex can vary according to the time interval between the transcranial magnetic stimulation and peripheral nerve stimulation. We established a model of cerebral ischemia in rats via transient middle cerebral artery occlusion. We administered paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks. We then evaluated spatial learning and memory using the Morris water maze. Changes in the cerebral ultra-structure and synaptic plasticity were assessed via transmission electron microscopy and a 64-channel multi-electrode array. We measured mRNA and protein expression levels of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 in the hippocampus using a real-time polymerase chain reaction and western blot assay. Paired associative stimulation treatment significantly improved learning and memory in rats subjected to cerebral ischemia. The ultra-structures of synapses in the CA1 area of the hippocampus in rats subjected to cerebral ischemia were restored by paired associative stimulation. Long-term potentiation at synapses in the CA3 and CA1 regions of the hippocampus was enhanced as well. The protein and mRNA expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1 increased after paired associative stimulation treatment. These data indicate that paired associative stimulation can protect cog-nition after cerebral ischemia. The observed effect may be mediated by increases in the mRNA and protein expression of brain-derived neurotrophic factor and N-methyl-D-aspartate receptor 1, and by enhanced synaptic plasticity in the CA1 area of the hippocampus. The animal experiments were approved by the Animal Ethics Committee of Tongji Medical College, Huazhong University of Science & Technology, China(approval No. TJ-A20151102) on July 11, 2015.

Stimulated electromagnetic emissions spectrum observed during an X-mode heating experiment at the European Incoherent Scatter Scientific Association

An extraordinary(X-mode)electromagnetic wave,injected into the ionosphere by the ground-based heating facility at Tromsφ,Norway,was utilized to modify the ionosphere on November 6,2017.The high-power high-frequency transmitter facility located at Tromsφ belongs to the European Incoherent Scatter Scientific Association.In the experiment,stimulated electromagnetic emission(SEE)spectra were observed.A narrow continuum occurred under cold-start conditions and showed an overshoot effect lasting several seconds.Cascading peaks occurred on both sides of the heating frequency only in the preconditioned ionosphere and also showed an overshoot effect.These SEE features are probably related to the ponderomotive process in the X-mode heating experiment and are helpful for understanding the physical mechanism that generated them during the X-mode heating experiment.The features observed in the X-mode heating experiments are novel and require further investigation.

Granulocyte colony-stimulating factor promotes growth of processes,growth associated protein 43 and microtubule-associated protein 2 expression in cultured rat retinal ganglion cells in vitro

Following granulocyte colony-stimulating factor （G-CSF） treatment,the growth of processes in cul-tured rat retinal ganglion cells （RGCs） in vitro,expression of growth associated protein 43,and expression of microtubule-associated protein 2 mRNA expression were significantly increased.In contrast,RhoA/Rock protein content was significantly reduced by G-CSF treatment.These results indicate that G-CSF promotes the growth of processes in RGCs and increases the expression of growth-associated protein 43 and microtubule-associated protein 2 mRNA by inhibiting the RhoA/Rock pathway,thereby benefiting axonal repair in RGCs exposed to hypoxia.

升白康复口服液联合PEG-rhG-CSF治疗乳腺癌化疗相关粒细胞减少临床效果

目的 分析联合使用升白康复口服液和聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)治疗乳腺癌化疗相关粒细胞减少临床效果。方法 选取首次化疗后出现Ⅲ~Ⅳ度骨髓抑制的乳腺癌患者100例为研究对象,以随机信封法分组,再次化疗结束后使用PEG-rhG-CSF治疗的患者为对照组(50例),在此基础上联合使用升白康复口服液治疗的患者为试验组(50例),治疗14 d,对比两组患者化疗前后白细胞(WBC)和中性粒细胞(ANC)水平变化情况、ANC分级及不良反应。结果 化疗后,两组患者WBC及ANC水平比化疗前均明显下降,试验组两项指标水平均高于对照组(P<0.01);化疗后,试验组ANC等级中Ⅰ度、Ⅱ度占比均高于对照组(P<0.01),Ⅲ度、Ⅳ级占比均低于对照组(P<0.01);试验组不良反应发生率低于对照组(P<0.05)。结论 联合使用升白康复口服液和PEG-rhG-CSF可减轻乳腺癌化疗相关粒细胞减少症,减轻不良反应。

甲状腺功能正常的2型糖尿病患者促甲状腺激素与代谢相关性脂肪肝的相关性研究

目的研究甲状腺功能正常的2型糖尿病(T2DM)患者促甲状腺激素(TSH)水平与代谢相关脂肪性肝病(MAFLD)的相关性。方法回顾分析我院内分泌科收治的甲状腺功能正常的T2DM患者1888例,根据是否合并MAFLD将其分为MAFLD组(1150例)和无MAFLD组(738例);依据TSH水平将所有患者进行四分位数分组(Q1~Q4组)。收集所有患者一般临床资料资料[年龄、性别、病程、BMI、腰围、MAFLD患病率、收缩压(SBP)和舒张压(DBP)]与实验室检查结果[ALT、AST、空腹葡萄糖(FPG)、血肌酐(SCr)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、糖化血红蛋白(HbA1c)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT_(4))、促甲状腺素(TSH)]并分组比较;采用多因素logistic回归分析评估甲状腺功能正常T2DM患者发生MAFLD的相关因素。结果MAFLD患病率为60.91%。MAFLD组BMI、腰围、ALT、AST、TG、LDL-C、TSH水平均显著高于无MAFLD组,FT3、FT_(4)及HDL-C水平均显著低于无MAFLD组(P<0.05)。Q1、Q2、Q3、Q4组MAFLD患病率依次升高;组间比较BMI、腰围、TG、HDL-C、FT_(4)水平差异有统计学意义(P<0.05)。多因素logistic回归分析结果显示,腰围、TG、TSH均是甲状腺功能正常T2DM患者发生MAFLD的独立危险因素,HDL-C是其保护因素(P<0.05)。结论甲状腺功能正常的T2DM患者TSH水平升高与MAFLD患病率相关。

加巴喷丁联合短时程神经电刺激治疗头面部带状疱疹性神经痛的临床效果

目的观察加巴喷丁联合短时程神经电刺激治疗头面部带状疱疹性神经痛的效果和安全性。方法选取2019年8月—2023年1月广州医科大学附属第六医院收治的70例急性期或亚急性期带状疱疹性神经痛患者作为研究对象,随机分为对照组与观察组,各35例。对照组给予加巴喷丁治疗,观察组同样剂量加巴喷丁联合短时程神经电刺激,均治疗4周。于患者治疗前(T_(0))及治疗后1周(T_(1))、2周(T_(2))、4周(T_(3))、2个月(T_(4))、3个月(T_(5))、6个月(T_(6))比较视觉模拟评分(visual analogue scale,VAS)、睡眠质量评分、不良反应,对患者的临床疗效进行评估。结果2组治疗后不同时间点VAS评分均低于治疗前(P<0.001);且观察组治疗后不同时间点VAS评分低于对照组,差异有统计学意义(P<0.05)。2组治疗后不同时间点睡眠质量评分均高于治疗前(P<0.001);观察组治疗后相同时间点睡眠质量评分高于对照组,但差异无统计学意义(P>0.05)。对照组不良反应总发生率为28.57%(10/35),观察组不良反应总发生率为5.71%(2/35),差异有统计学意义(P<0.05)。结论加巴喷丁联合短时程神经电刺激治疗头面部带状疱疹性神经痛能减轻患者疼痛程度,改善睡眠质量且安全性高,总体疗效更优。

急性冠脉综合征患者血清sST2及NLRP3水平与介入术后无复流-慢血流的相关性分析

目的探讨急性冠脉综合征(acute coronary syndrome,Acs)患者血清可溶性生长刺激表达基因蛋白2(soluble growth stimulation expression gene 2 protein,sST2),核苷酸寡聚化结构域样受体热蛋白结构域相关蛋白3(nucleotide oligomerization domain like receptor heat protein domain associated protein 3,NLRP3)水平与经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后无复流-慢血流的关系。方法选择2020年1月~2022年12月佳木斯市中心医院收治的97例急性冠脉综合征患者,所有患者均接受PCI治疗,根据术后无复流-慢血流发生情况分为无复流-慢血流组(n=20)和对照组(n=77)。术前检测血清sST2及NLRP3水平,分析影响急性冠脉综合征患者PCI术后无复流-慢血流的因素以及sST2,NLRP3预测急性冠脉综合征患者PCI术后无复流-慢血流的价值。结果无复流-慢血流组血清sST2(14.32±2.65 ng/ml vs 11.02±2.13 ng/ml),NLRP3(68.23±10.17 pg/ml vs 42.05±8.23 pg/ml)水平高于对照组,差异具有统计学意义(t=5.860,12.055,均P<0.05)。多因素Logistic回归分析显示高血栓负荷(OR:7.791,95%CI:2.834~21.421)、高水平sST2(OR=2.071,95%CI:1.146~3.743)、高水平NLRP3(OR=2.008,95%CI:1.228~3.284)是急性冠脉综合征患者PCI术后无复流-慢血流的危险因素(均P<0.05)。sST2,NLRP3诊断急性冠脉综合征患者PCI术后无复流-慢血流的临界值分别为12.91ng/ml,55.39 pg/ml,曲线下面积分别为0.737,0.686,联合sST2,NLRP3诊断急性冠脉综合征患者PCI术后无复流-慢血流的曲线下面积为0.907,高于单独诊断(Z=2.662,2.856,均P<0.05)。结论急性冠脉综合征患者血清sST2,NLRP3水平增高与PCI术后无复流-慢血流的发生有关,联合检测sST2和NLRP3可提高对术后无复流-慢血流的诊断效能。

Effects of repetitive transcranial magnetic stimulation on adenosine triphosphate content and microtubule associated protein-2 expression after cerebral ischemia-reperfusion injury in rat brain

Background Repetitive transcranial magnetic stimulation （rTMS） research has mainly been focused on the therapeutic effect of psychiatric disorders and Parkinson＇s disease. A few studies have shown that rTMS might protect against delayed neuronal death induced by transient ischemia, enhance long-term potentiation in ischemic conditions and affect regional brain blood flow and metabolism. The aim of this study was to determine the effects of repetitive transcranial magnetic stimulation （rTMS） on adenosine triphosphate （ATP） content and microtubule associated protein-2 （MAP-2） expression in rat brain after middle cerebral artery occlusion （MCAO）/reperfusion. Methods To study the effects of different timecourses of rTMS on ATP content and MAP-2 expression, 90 rats were randomly divided into three groups （30 rats in each group）. To study the effects of multiple rTMS parameters on ATP content and MAP-2 expression, the rats in each group were further divided into six subgroups （five rats each）. The rats were sacrificed at 1-hour, 24-hour and 48-hour intervals after reperfusion, and the brain tissues were collected for the detection of ATP and MAP-2. Results rTMS could significantly increase ATP content and MAP-2 expression in the left brain following ischemic insult （P 〈0.01） and different rTMS parameters had different effects on the ATP level and the MAP-2 expression in the left striatum. A high-frequency rTMS played an important role in MAP-2 expression and ATP preservation. Conclusions This study revealed that rTMS induced significant increase of ATP content and MAP-2 expression in the injured area of the brain, suggesting that the regulation of both ATP and MAP-2 may be involved in the biological mechanism of the effect of rTMS on neural recovery. Therefore, rTMS may become a potential adjunctive therapy for ischemic cerebrovascular disease.

肠上皮脂解刺激脂蛋白受体减轻葡聚糖硫酸钠诱导的小鼠结肠炎

目的:探索脂解刺激脂蛋白受体(lipolysis-stimulated lipoprotein receptor,LSR)在葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的结肠炎小鼠中的表达变化,以及肠上皮Lsr特异性敲除及过表达对结肠炎小鼠肠道炎症的影响。方法:C57BL/6J小鼠饮水中加入浓度为3%(w/v)的DSS,自由饮用6 d诱导小鼠结肠炎模型;实验结束后,通过RNA-seq对对照组和实验组中差异表达的基因进行筛选,通过RT-qPCR、Western blot和免疫荧光染色的方法检测LSR表达变化。接下来,通过Cre-loxP系统构建肠上皮Lsr特异性敲除小鼠,建立DSS诱导的结肠炎模型,检测体重变化、疾病活动度指数(disease activity index,DAI)评分、结肠长度并进行HE染色来评估小鼠肠炎症状;同时,通过ELISA检测血清中促炎细胞因子肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin-1β,IL-1β)、IL-6和IL-18水平;免疫荧光染色检测结肠组织中性粒细胞和巨噬细胞浸润情况;PAS染色观察杯状细胞数量。最后,腹腔注射腺相关病毒(AAV-Lsr)构建LSR过表达小鼠,确定LSR过表达成功后,通过上述方法诱导小鼠结肠炎模型后观察肠道炎症情况。结果:LSR在DSS诱导的结肠炎小鼠中表达下调,同时,肠上皮Lsr特异性敲除小鼠对DSS诱导的结肠炎的易感性增加,表现为体重显著减轻(P<0.05),DAI得分显著升高(P<0.01),结肠长度显著缩短(P<0.05),病理损伤加重,促炎细胞因子TNF-α(P<0.05)、IL-1β(P<0.01)、IL-6(P<0.05)和IL-18(P<0.01)水平显著升高,炎症细胞浸润增加,结肠杯状细胞数量减少。此外,LSR过表达显著减轻DSS诱导的结肠炎小鼠肠道炎症。结论:LSR在DSS诱导的结肠炎小鼠中表达降低,LSR缺失加重DSS诱导的结肠炎小鼠的肠道炎症,AAV介导LSR过表达能减轻DSS诱导的结肠炎小鼠的肠道炎症。

加味五子衍宗丸治疗黄体功能不全不孕症患者的效果及对雌性激素、PAPP-A、VEGF的影响

目的分析加味五子衍宗丸治疗黄体功能不全(LPD)不孕症患者的效果及对雌性激素、妊娠相关蛋白(PAPP-A)、血管内皮生长因子(VEGF)的影响。方法选取2021年11月—2022年12月收治的160例LPD所致肾虚精亏证不孕症。采用随机数字表法分为对照组和研究组,各80例。对照组采用地屈孕酮片治疗,研究组在对照组基础上联用加味五子衍宗丸治疗,均治疗3个月经周期。比较2组临床疗效、妊娠成功率及治疗期间不良反应发生情况。比较治疗前后中医证候积分、血清PAPP-A、VEGF、卵泡素(FSH)、促黄体生成素(LH)、雌二醇(E_(2))和孕酮水平。结果研究组总有效率为93.75%(75/80)高于对照组的82.50%(66/80)(P<0.05)。治疗后,研究组FSH、LH、E_(2)、孕酮、PAPP-A、VEGF水平高于对照组(P<0.05)。随访3个月经周期,研究组妊娠成功率为51.25%(41/80)明显高于对照组的35.00%(28/80)(P<0.05)。2组治疗期间均无药物不良反应发生。结论地屈孕酮片联合加味五子衍宗丸治疗LPD所致肾虚精亏证不孕症获得较好临床效果,调节患者内分泌代谢,提高血清PAPP-A、VEGF水平,提高妊娠成功率。

Paired associative stimulation modulates corticomotor excitability in chronic stroke: A preliminary investigation

BACKGROUND AND OBJECTIVE Paired associative stimulation (PAS) combining repeated pairing of electrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear.

Involvement of different neuronal components in the induction of cortical plasticity with associative stimulation

BACKGROUND AND OBJECTIVE Paired associative stimulation (PAS), with stimulus interval of 21.5 or 25 ms, using transcranial magnetic stimulation in the posterior-anterior (PA) current direction, produces a long-term-potentiation-like effect. Stimulation with PA directed current generates both early and late indirect (I)-waves while that in anterior-posterior (AP) current predominantly elicits late I-waves. Short interval intracortical inhibition (SICI) inhibits late I-waves but not early I-waves.To investigate how cortical inhibition modulates the effects of PAS.

Paired associative stimulation modulates corticomotor excitability in chronic stroke

BACKGROUND Paired associative stimulation (PAS) combining repeated pairing of lectrical stimulation of a peripheral nerve with transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) can induce neuroplastic adaptations in the human brain and enhance motor learning in neurologically-intact individuals. However, the extent to which PAS is an effective technique for inducing associative plasticity and improving motor function in individuals post-stroke is unclear.OBJECTIVE The objective of this pilot study was to investigate the effects of a single session of PAS to modulate corticomotor excitability and motor skill performance in individuals post-stroke.METHODS Seven individuals with chronic stroke completed two separate visits separated by at least one week. We assessed general corticomotor excitability, intracortical network activity and behavioral outcomes prior to and at three time points following PAS and compared these outcomes to those following a sham PAS condition (PASSHAM).RESULTS Following PAS, we found increased general corticomotor excitability but no significant difference in behavioral measures between PAS conditions. There was a relationship between PAS-induced corticomotor excitability increase and enhanced motor skill performance across post-PAS testing time points.CONCLUSION These results provide preliminary evidence for the potential of PAS to increase corticomotor excitability that could favorably impact motor skill performance in chronic individuals post-stroke and are an important first step for future studies investigating the clinical application and behavioral relevance of PAS interventions in post stroke patient populations.

Visuomotor task acquisition is reduced by priming paired associative stimulation in older adults

BACKGROUND AND OBJECTIVES Transcranial magnetic stimulation may represent an effective means for improving motor function in the elderly. The aim of this study was therefore to investigate the effects of paired associative stimulation (PAS;a plasticity-inducing transcranial magnetic stimulation paradigm) on acquisition of a novel visuomotor task in young and older adults.METHODS Fourteen young (20.4±0.6 years) and 13 older (69.0±1.6 years) adults participated in 3 experimental sessions during which training was preceded (primed) by PAS. Within each session, the interstimulus interval used for PAS was set at either the N20 latency plus 5 ms (PASLTP), the N20 latency minus 10 ms (PASLTD), or a constant 100 ms (PASControl).RESULTS After training, the level of motor skill was not different between PAS conditions in young subjects (all p-values > 0.2), but was reduced by both PASLTP (P=0.02) and PASLTD (P=0.0001) in older subjects.CONCLUSION Priming PAS was detrimental to skill acquisition in older adults, possibly suggesting a need for interventions that are optimized for use in elderly populations.

Determinants of inter-individual variability in corticomotor excitability induced by paired associative stimulation

BACKGROUND AND OBJECTIVES Transcranial magnetic stimulation(TMS)is a well-established tool in probing cortical plasticity in vivo.Changes in corticomotor excitability can be induced using paired associative stimulation(PAS)protocol,in which TMS over the primary motor cortex is conditioned with an electrical peripheral nerve stimulation of the contralateral hand.PAS with an inter-stimulus interval of 25 ms induces long-term potentiation(LTP)-like effects in cortical excitability.However,the response to a PAS protocol tends to vary substantially across individuals.In this study,we used univariate and multivariate data-driven methods to investigate various previously proposed determinants of inter-individual variability in PAS efficacy,such as demographic,cognitive,clinical,neurophysiological,and neuroimaging measures.METHODS Forty-one right-handed participants,comprising 22 patients with amnestic mild cognitive impairment(MCI)and 19 healthy controls(HC),underwent the PAS protocol.Prior to stimulation,demographic,genetic,clinical,as well as structural and resting-state functional MRI data were acquired.RESULTS The two groups did not differ in any of the variables,except by global cognitive status.Univariate analysis showed that only 61%of all participants were classified as PAS responders,irrespective of group membership.Higher PAS response was associated with lower TMS intensity and with higher resting-state connectivity within the sensorimotor network,but only in responders,as opposed to non-responders.We also found an overall positive correlation between PAS response and structural connectivity within the corticospinal tract,which did not differ between groups.A multivariate random forest(RF)model identified age,gender,education,IQ,global cognitive status,sleep quality,alertness,TMS intensity,genetic factors,and neuroimaging measures functional and structural connectivity,gray matter(GM)volume,and cortical thickness as poor predictors of PAS response.The model resulted in low accuracy of the RF classifier(58%;95%CI:42-74%),with a higher relative importance of brain connectivity measures compared to the other variables.CONCLUSION S We conclude that PAS variability in our sample was not well explained by factors known to influence PAS efficacy,emphasizing the need for future replication studies.

Bilateral motor cortex plasticity in individuals with chronic stroke,induced by paired associative stimulation

BACKGROUND AND OBJECTIVE In the chronic phase after stroke, cortical excitability differs between the cerebral hemispheres;the magnitude of this asymmetry depends on degree of motor impairment. It is unclear whether these asymmetries also affect capacity for plasticity in corticospinal tract excitability or whether hemispheric differences in plasticity are related to chronic sensorimotor impairment. METHODS Response to paired associative stimulation (PAS) was assessed bilaterally in 22 individuals with chronic hemiparesis.

Long-term paired associative stimulation enhances motor output of the tetraplegic hand

BACKGROUND AND OBJECTIVES A large proportion of spinal cord injuries (SCI) are incomplete. Even in clinically complete injuries, silent non-functional connections can be present. Therapeutic approaches that can strengthen transmission in weak neural connections to improve motor performance are needed. Our aim was to determine whether long-term delivery of paired associative stimulation (PAS, a combination of transcranial magnetic stimulation [TMS] with peripheral nerve stimulation [PNS]) can enhance motor output in the hands of patients with chronic traumatic tetraplegia, and to compare this technique with long-term PNS.METHODS Five patients (4 males;age 38-68, mean 48) with no contraindications to TMS received 4 weeks (16 sessions) of stimulation. PAS was given to one hand and PNS combined with sham TMS to the other hand. Patients were blinded to the treatment. Hands were selected randomly. The patients were evaluated by a physiotherapist blinded to the treatment. The follow-up period was 1 month. Patients were evaluated with Daniels and Worthingham’s Muscle Testing (0-5 scale) before the first stimulation session, after the last stimulation session, and 1 month after the last stimulationsession.RESULTS One month after the last stimulation session, the improvement in the PAS-treated hand was 1.02±0.17 points (P<0.0001,n=100 muscles from 5 patients). The improvement was significantly higher in PAS-treated than in PNS-treated hands (176±29%,P=0.046,n=5 patients).CONCLUSION Long-term PAS might be an effective tool for improving motor performance in incomplete chronic SCI patients. Further studies on PAS in larger patient cohorts, with longer stimulation duration and at earlier stages after the injury, are warranted.