经颅电刺激镇痛研究的现状及展望

经颅电刺激技术是一种非侵入性神经调控方法,因其具有卓越的安全性、良好的患者依从性以及高度便携性等特点,被视为一种潜在的非药物镇痛手段。然而,目前对于经颅电刺激镇痛效果的研究结果不一致且镇痛机制尚未完全阐明。本文通过系统归纳总结3种主要的经颅电刺激技术——经颅直流电刺激、经颅交流电刺激和经颅随机噪声刺激——在镇痛领域的研究进展,评估了这些技术对短时、急性和慢性疼痛的镇痛效果,并深入剖析了其潜在的镇痛机制。同时,本文系统讨论了既往研究的局限性,并对未来研究提出了一系列切实可行的建议,如借助电场模拟技术实现个性化刺激以克服不同个体头部解剖结构差异的影响、应用多位点刺激和深部脑刺激技术来拓展刺激脑区、搭建经颅电刺激技术同步神经影像平台以制定个体特异性的刺激方案并深入揭示其镇痛机制、探索与其他治疗技术的联合应用以提高疗效等。这些建议的实施将有助于解决当前研究中存在的问题,充分发挥经颅电刺激在疼痛治疗中的临床价值,最终实现患者疼痛的缓解。     

经颅磁刺激和经颅直流电刺激在调控大脑共情功能中的应用

共情可以帮助人们建立和谐的人际关系，更好地适应现实社会，是一种重要的社会认知功能。已有研究表明，诸多神经和精神类疾病的发生发展和复发与共情缺陷有关。非侵入性脑刺激技术（经颅磁刺激和经颅直流电刺激）可以通过调节大脑皮层兴奋性来调控个体的共情水平，缓解共情缺陷症状。针对健康群体使用该技术的现有证据显示：内侧前额叶、初级运动皮层、额下回、背外侧前额叶和颞顶交界处的活动有助于提升个体的认知共情水平，其中双侧背外侧前额叶的活动还有助于下调个体的情感共情水平，而右侧颞顶交界处的活动则可以增强自我表征从而支持个体在共情时进行自我和他人的区分。少数针对共情缺陷群体使用该技术的临床证据提示，增强左侧背外侧前额叶和内侧前额叶的活动可以分别提升精神疾病和神经退行性疾病患者的认知共情水平。未来的研究应探讨在统一的行为测量范式下针对不同刺激参数和刺激位点进行共情干预研究，通过融合其他神经生理技术进一步考察非侵入性脑刺激技术改善共情功能的作用机制，并考虑个体差异性对大脑共情功能干预效果的影响。     

综述: 无创穿颅电刺激对人脑神经活动和认知功能的调控

穿颅电刺激被认为可以无创调节大脑的神经活动,为研究特定脑区与某一认知功能间的因果关系提供了可能.近些年,对穿颅电刺激作用机制和其对认知、运动功能调控的研究方面取得了很多重要进展.在这篇综述中,我们总结了以往关于穿颅直流电刺激、穿颅交流电刺激和穿颅随机噪声电刺激三种刺激方式的发展历史及其作用机制,同时总结了其对感知觉(主要是视觉知觉)、注意和记忆等认知功能的调控,并对未来的研究方向进行了展望.     

Do changes in spinal reflex excitability elicited by transcranial magnetic stimulation differ based on the site of cerebellar stimulation?

Abstract

Purpose: The present study aimed to investigate whether spinal reflex excitability is influenced by the site of cerebellar transcranial magnetic stimulation (C-TMS).

Materials and methods: Fourteen healthy volunteers (mean age: 24.6?±?6.6?years [11 men]) participated. Participants lay on a bed in the prone position, with both ankle joints fixed to prevent unwanted movement. Right tibial nerve stimulation was provided to elicit the H-reflex in the right soleus muscle. Conditioning transcranial magnetic stimulation (TMS) was delivered at one of the following sites 110?ms prior to tibial stimulation: right, central, or left cerebellum; midline parietal (Pz) region; or sham stimulation. A total of 10 test trials were included for each condition, in random order. The unconditioned and conditioned H-reflexes were measured during random inter-test trials, and the cerebellar spinal facilitation (CSpF) ratios for each site were calculated (the ratio of conditioned to unconditioned H-reflexes). CSpF ratios were compared among TMS sites.

Results: CSpF ratios were significantly higher at cerebellar sites than at the Pz site or during sham stimulation. However, there was no significant difference in CSpF ratio among cerebellar sites.

Conclusions: TMS conditioning over any part of the cerebellum facilitated the excitability of the spinal motoneuron pool. Facilitation of the H-reflex due to C-TMS may involve the effects of the bilateral descending tract of the spinal cord on the spinal motoneuron pool. Alternatively, direct brainstem stimulation may have activated portions of the bilateral descending tract of the spinal cord.     

Reduction in cortical parvalbumin expression due to intermittent theta‐burst stimulation correlates with maturation of the perineuronal nets in young rats

We recently showed that intermittent theta‐burst stimulation (iTBS) using transcranial magnetic stimulation strongly reduces the number of rat neocortical interneurons expressing glutamic acid decarboxylase 67 kDa (GAD67) and parvalbumin (PV), indicating changed activity of fast‐spiking (FS) interneurons. In advance of in vitro studies intended to characterize changes in electrical properties of FS interneurons under these conditions, we tested whether the iTBS effect is age‐dependent. Conscious Sprague‐Dawley rats aged between 28 and 90 days received three blocks of iTBS at 15 min intervals. We found that iTBS‐related reduction in PV+ cells was absent up to an age of 32 days, then gradually increased, and approached a maximum of about 40% reduction at an age of about 40 days. The relative number of cells expressing PV (PV+, 8–9%) did not change with age in sham‐controls and also the increase in cortical c‐Fos expression induced by iTBS was not principally age‐dependent. However, a prominent growth of the perineuronal nets, typically surrounding the PV+ cells, exactly paralleled the increase in the iTBS effect. Based on these findings, we conclude that the functional development of the inhibitory network of PV+ interneurons with regard to intracortical synaptic connectivity is not sufficiently matured in rats younger than 35d to enable activity‐dependent modifications during iTBS. Outgrowth of the perineuronal nets and associated maturation of excitatory cortical inputs, as is characteristic for the critical cortical period, may take place before PV+ interneurons can be sufficiently activated via repetitive transcranial magnetic stimulation, allowing plastic changes of molecular phenotype and likely also synaptic plasticity. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 1–11, 2015     

Segmental release of amino acid neurotransmitters from transcranial stimulation

The present study used microdialysis techniques in an intact rabbit model to measure the release of amino acids within the lumbar spinal cord in response to transcranial electrical stimulation. Dialysis samples from the extracellular space were obtained over a stimulation period of 90 minutes and were examined using high pressure liquid chromatography. Neuronal excitation was verified by recerding corticomotor evoked potentials (CMEPs) from the spinal cord. A significant increase in the release of glycine and taurine compared to sham animals was measured after 90 minutes of transcranial stimulation. Glutamate and aspartate release was not significantly elevated. GABA concentrations were consistently low. CMEP components repeatedly showed adequate activation of descending fiber pathways and segmental interneuron pools during dialysis sampling. Since glycine, and to a lesser extent taurine, have been shown to inhibit motor neuron activity and are closely associated with segmental interneuron pools, suprasegmental modulation of motor activity may be, in part, through these inhibitory amino acid neurotransmitters in the rabbit lumbar spinal cord.     

Effects of transcranial direct current stimulation (tDCS) on balance improvement: a systematic review and meta-analysis

Background: Transcranial direct current stimulation (tDCS) has emerged as a promising therapeutic tool to improve balance and optimize rehabilitation strategies. However, current literature shows the methodological heterogeneity of tDCS protocols and results, hindering any clear conclusions about the effects of tDCS on postural control.

Objective: Evaluate the effectiveness of tDCS on postural control, and identify the most beneficial target brain areas and the effect on different populations.

Methods: Two independent reviewers selected randomized tDCS clinical-trials studies from PubMed, Scopus, Web of Science, and reference lists of retrieved articles published between 1998 and 2017. Most frequently reported centre of pressure (COP) variables were selected for meta-analysis. Other postural control outcomes were discussed in the review.

Results: Thirty studies were included in the systematic review, and 11 were submitted to a meta-analysis. A reduction of COP displacement area has been significantly achieved by tDCS, evidencing an improvement in balance control. Individuals with cerebral palsy (CP) and healthy young adults are mostly affected by stimulation. The analysis of the impact of tDCS over different brain areas revealed a significant effect after primary motor cortex (M1) stimulation, however, with no clear results after cerebellar stimulation due to divergent results among studies.

Conclusions: tDCS appears to improve balance control, more evident in healthy and CP subjects. Effects are observed when primary MI is stimulated. Cerebellar stimulation should be better investigated.     

精准定位脑刺激对运动功能调控研究进展

脑刺激是神经科学研究的重要手段,传统的经颅磁刺激和经颅电刺激等脑刺激方法尽管能调控运动功能(包括减轻运动性障碍疾病的运动障碍、提高运动能力等),但存在空间分辨率低且无法刺激深部脑组织的局限性.近年来迅速发展的深部脑刺激(deep brain stimulation,DBS)、光遗传学、经颅超声刺激(transcranial ultrasound stimulation,TUS)、时间干涉(temporal interference,TI)等精准定位脑刺激方法,具有空间分辨率高、可聚焦深部脑组织等优点.本文综述了上述几种脑刺激方法的原理、特点,对运动功能调控的研究进展,以及面临的挑战和发展前景,从而为神经科学研究提供更好的研究工具,为临床实践提供更多的干预治疗手段.     

The epigenetic component of the brain response to electromagnetic stimulation in Parkinson's Disease patients: A literature overview

Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non‐coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic‐based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS). Notwithstanding the proven efficacy of EM therapies, the precise molecular mechanisms underlying the brain response to these types of stimulations are still far from being elucidated. In this review we provide an overview of the epigenetic changes triggered by DBS and TMS in both PD patients and neurons from different experimental animal models. Furthermore, we also propose a critical overview of the exposure modalities currently applied, in order to evaluate the technical robustness and dosimetric control of the stimulation, which are key issues to be carefully assessed when new molecular findings emerge from experimental studies. Bioelectromagnetics. 39:3–14, 2018. © 2017 Wiley Periodicals, Inc.     

重复经颅磁刺激对慢性精神分裂症患者认知功能影响的初步研究

目的:探讨重复经颅磁刺激(rTMS)对慢性精神分裂症患者认知功能的影响。方法:100例慢性精神分裂症患者,按照随机数字表法分为rTMS真刺激组和伪刺激组,每组各50例。采用阳性与阴性症状量表(PANSS)及副反应量表(TESS)评估患者治疗前后精神症状及不良反应;采用威斯康星卡片分类测验(WCST)及可重复的成套神经心理状态测量(RBANS)评价患者治疗前后认知功能。结果:治疗后,rTMS真刺激组PANSS总分、阳性量表分、阴性量表分、一般精神病理量表分均明显降低(P0.05),且均明显低于伪刺激组(P0.05),两组治疗前后及组间TESS评分无明显差异(P0.05);rTMS真刺激组WCST中的概念化水平百分数明显高于伪刺激组(P0.05),总时间及错误思考时间短于伪刺激组(P0.05);rTMS真刺激组RBANS中视觉广度与延迟记忆成绩明显提高(P0.05),且视觉广度明显高于伪刺激组(P0.05);rTMS真刺激组2例患者首次治疗后出现轻度不适症状,随访3个月所有患者均无不适主诉。结论:rTMS治疗对慢性精神分裂症患者的部分认知功能有一定的改善作用,且安全性较高,值得进一步研究。     

Therapeutic staff exposure to magnetic field pulses during TMS/rTMS treatments

Transcranial magnetic stimulation or repetitive transcranial magnetic stimulation (TMS/rTMS) is currently being used in treatments of the central nervous system diseases, for instance, depressive states. The principles of localized magnetic stimulation are summarized and the risk and level of occupational field exposure of the therapeutic staff is analyzed with reference to ICNIRP guidelines for pulses below 100 kHz. Measurements and analysis of the occupational exposure to magnetic fields of the staff working with TMS/rTMS are presented.     

创伤后应激障碍的经颅磁刺激研究进展

创伤后应激障碍会损伤记忆、注意和执行等认知功能,引起异常的脑活动及脑区间功能连接.尽管药物治疗和心理干预能够取得一定的治疗效果,但存在药物副作用和起效延迟等问题.经颅磁刺激作为新的创伤后应激障碍干预手段受到越来越多的关注.本文通过综述经颅磁刺激干预创伤后应激障碍以及调控认知功能和脑活动的相关研究,系统探讨了创伤后应激障碍干预中经颅磁刺激模式、刺激靶点和疗效评估等问题,并提出未来借助更有效的技术手段进行定位、建立全面有效的评估体系和结合新的记忆理论探索具有长期临床改善效果的干预方案.     

Is high-frequency repetitive transcranial magnetic stimulation of the left primary motor cortex superior to the stimulation of the left dorsolateral prefrontal cortex in fibromyalgia syndrome?

Objective: To investigate effectiveness of two different high-frequency repetitive transcranial magnetic stimulation (rTMS) protocols on pain, fatigue, quality of life (QoL) and depression in female patients with fibromyalgia.

Methods: Thirty patients were randomized into three groups. Fifteen sessions of 10?Hz (90% resting motor threshold-RMT, 1200 pulses) rTMS were applied to left primary motor cortex and left dorsolateral prefrontal cortex (DLPFC) in Group M1 (n:10) and Group DLPFC (n:10), respectively. Group sham (n?=?10) received 15 sessions of sham rTMS over 3?weeks. Visual Analogue Scale, Fibromyalgia Impact Questionnaire, Fatigue Severity Scale, Short-form 36, and Beck Depression Inventory were assessed at baseline and at the end of the treatments by a blinded-experienced assessor.

Results: Significant improvements in pain, QoL, and depression scores were observed in three groups. However, improvements in depression, physical functioning, physical role functioning, and general health perceptions were greater in active rTMS groups than in sham group. Emotional role functioning was only improved in Group M1. The decrease in VAS scores was significantly greater in Group M1 when compared to sham group. Change in physical role functioning was significantly greater in Group DLPFC than in Group M1.

Conclusions: Significant improvements in physical role functioning, physical functioning, depression, and general health perceptions were achieved in active rTMS groups. Further clinical studies on larger samples involving both sexes with longer follow-up durations are needed.     

重复经颅磁刺激对脑卒中后患者神经功能缺损的改善

目的:探讨重复经颅磁刺激在脑卒中康复的应用及效果.方法:选择2010年9月至2012年9月在我院神经内科收治的58例脑卒中患者分为两组,即A组和B组,A组患者给予常规药物治疗和康复训练,B组患者在上述治疗的基础上加用低频重复经颅磁刺激治疗,比较两组患者美国国立卫生院神经功能缺损评分情况、日常生活活动(ADL)评分和不良反应发生情况.结果:治疗后,随着时间的推移,两组患者美国国立卫生院神经功能缺损评分得分逐渐下降(P＜0.05).B组患者2周后和6周后两个时点美国国立卫生院神经功能缺损评分得分明显低于A组患者的,差异有显著性(P＜0.05),而随着时间的推移,两组患者日常生活活动(ADL)评分得分逐渐上升(P＜0.05).B组患者2周后和6周后两个时点日常生活活动(ADL)评分得分明显高于A组患者的,差异有显著性(P＜0.05).两组患者在不良反应发生方面差异无显著性(P＞0.05).结论:低频重复经颅磁刺激治疗脑卒中单侧肢体功能障碍患者临床疗效确切,安全可靠,不良反应少.     

Neural circuits underlying motor facilitation during observation of implied motion

Abstract

In the present study we used single and paired-pulse Transcranial Magnetic Stimulation (TMS) to evaluate the effect of implied motion on primary motor cortex microcircuits. We found that observation of the implied motion of a static image increases MEP amplitude and reduces short-interval intracortical inhibition (SICI), without significant modulation of intracortical facilitation and sensory-motor integration. Our results add to the existing literature on the activation of the observation-execution matching system and describe a selective modulation of GABAergic cortical microcircuits during observation of implied motion.     

Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation

Partial sleep deprivation (PSD) has a profound and rapid effect on depressed mood. However, the transient antidepressant effect of PSD - most patients relapse after one night of recovery sleep - is limiting the clinical use of this method. Using a controlled, balanced parallel design we studied, whether repetitive transcranial magnetic stimulation (rTMS) applied in the morning after PSD is able to prevent this relapse. 20 PSD responders were randomly assigned to receive either active or sham stimulation during the following 4 days after PSD. Active stimulation prolonged significantly (p < 0.001) the antidepressant effect of PSD up to 4 days. This finding indicates that rTMS is an efficacious method to prevent relapse after PSD.     

Phase-dependent modulation of corticospinal excitability during the observation of the initial phase of gait

This study was undertaken to identify the temporal characteristics of corticospinal excitability of tibialis anterior muscle during the observation of the initial phase of gait. For this purpose, using transcranial magnetic stimulation, we recorded motor evoked potentials (MEPs) during the observation of the second step of an actor’s first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface. The results demonstrate that (1) MEPs during the observation of the initial phase of normal gait were significantly increased only at early swing phase, but not other phases (mid-swing, heel contact, mid-stance, and heel off) and (2) MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases. These findings provide the first evidence that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demanded-dependent manners.