重复经颅磁刺激治疗卒中后认知障碍的研究进展

认知障碍是卒中后常见并发症，严重影响患者康复进程及生活质量。重复经颅磁刺激 （repetitive transcranial magnetic stimulation，rTMS）作为一种新型的非侵入性神经电生理技术，通过改 变神经细胞动作电位影响脑内代谢和神经电活动，近年来逐渐被用于卒中后认知障碍的治疗。目前 rTMS在卒中后执行功能、记忆功能、语言能力及视空间能力的康复应用中均取得了较为积极的疗效， 且在指南推荐的治疗参数范围内操作基本是安全的，但仍缺乏大样本、多中心、高质量的随机对照 试验进一步明确其最佳刺激参数与治疗效果。rTMS治疗卒中后认知障碍的研究仍处于探索阶段，未 来有望进行更深入的机制研究，为rTMS治疗卒中后认知功能障碍提供更切实有力的依据。     

重复经颅磁刺激改善缺血性脑卒中运动功能的作用机制

缺血性脑卒中是世界范围内导致长期运动功能残疾的主要原因.脑卒中后运动功能的恢复很大程度上依赖于人脑的可塑性潜力.重复经颅磁刺激(rTMS)是一项能改变人类脑皮质兴奋性的无创、无痛且相对安全的方法,它可通过调整患者脑组织可塑性促进功能康复.此文简要综述rTMS在缺血性脑卒中运动功能恢复中的作用机制.     

经颅直流电刺激在卒中后吞咽障碍康复治疗中的应用研究进展

卒中后吞咽障碍可能是由吞咽皮质中枢、皮质下行纤维、延髓吞咽中枢及锥体外系损伤 所致,目前尚无特异性治疗方法,临床干预以直接训练和间接训练等康复治疗为主。经颅直流电刺激 （transcranial direct current stimulation,tDCS）是通过直流电刺激来改变神经可塑性和皮质兴奋性,以 改善各种神经、精神疾病的神经刺激治疗手段。近年来,研究者逐渐重视tDCS对大脑活动的调节作 用和生理效应,并对tDCS刺激神经网络的作用机制展开探索。本研究从tDCS的神经作用机制、刺激 参数以及刺激后效应等方面阐述tDCS的研究进展,以期为卒中后吞咽障碍患者寻找有效的康复方式, 并为未来的研究提供依据。     

重复经颅磁刺激治疗脑梗死后偏瘫的研究进展

脑梗死又称缺血性卒中,是全球致残率及致死率较高的疾病。尽管对脑梗死患者进行了全面的康复治疗,但大多数患者仍会遗留残疾,直接影响生活质量、日常生活能力,增加患者家庭和社会的经济负担。因此,促进脑梗死患者运动功能的恢复尤为重要,这需要在临床实践中有更多新的治疗选择。重复经颅磁刺激作为一个无痛、无创的治疗方法,已被证实可有效改善脑梗死后偏瘫肢体的运动功能,从而提高患者生活质量。目前,重复经颅磁刺激治疗的基础研究和临床研究都有了新进展,故此进行综述,以期对临床工作有一定帮助。     

JAMA Neurol：小脑间歇性θ-脉冲刺激改善卒中患者步态和平衡功能障碍

<正>卒中后肢体功能障碍会引起步态和平衡功能受损,而步态和平衡障碍是不良功能预后的决定性因素之一。因为步态是独立生活的关键因素,改善步行功能是卒中康复的主要目标。平衡功能障碍对功能独立性和机体整体恢复也有重要影响。然而,卒中患者的步态康复仍然缺乏先进的康复方案。恢复期,对侧小脑参与到卒中后运动网络的功能重组,并发挥重要作用。在卒中动物模型中,刺激小脑皮层网络能够改善功能恢复。值得注意的是,fMRI研究显示对侧小脑神经活性与卒中患者的步态恢复呈正     

脑缺血后突触可塑性与神经胶质细胞相互调控在神经修复中的作用

脑卒中是具有较高病死率和致残率的疾病,呈现逐年上升和年轻化趋势,严重危害健康。缺血性卒中主要是由于缺血和缺氧造成神经细胞的损伤,最终导致大脑功能的丧失,且治疗选择有限。目前认为突触可塑性是局灶性缺血后神经恢复的重要过程,神经胶质细胞与突触可塑性密切相关,若能深入了解神经元突触可塑性的作用、神经胶质细胞与突触可塑性相互调控机制,则可能对脑缺血后功能恢复提供一定的帮助。本文就突触可塑性、神经胶质细胞与突触可塑性相互调控作用进行综述,以期为治疗脑缺血后神经功能损伤提供理论支持。     

小脑卒中后非运动功能障碍的研究进展

目前对小脑非运动功能的新认识是基于神经解剖学、神经影像学和临床研究的综合证据,临床上对其认识不足,因此小脑卒中患者的非运动功能损害症状常常被忽视。目前研究认为小脑的非运动功能主要包括认知、语言及情绪、情感等方面。本文主要从解剖、小脑非运动功能的神经调控模式和临床表现等方面对小脑卒中后非运动功能障碍的研究进展进行阐述。     

小脑靶向神经刺激促进吞咽恢复机制的研究进展

大脑的经颅磁刺激和电刺激是目前具有一定应用前景的技术,逐渐在基础研究和临床实 践中得到应用。这种无创的、非侵入性的靶向神经刺激,通过调节神经兴奋性和可塑性来改善或恢复 大脑功能。由于小脑在运动协调、联想和情感等方面与大脑存在神经解剖和功能联系,因此以小脑为 靶点的神经刺激可以更好地了解生理及病理状态下,小脑与大脑吞咽运动区之间的联系,更好地研究 小脑对吞咽皮质区域兴奋性的调节作用,以及对吞咽功能的影响,为神经源性吞咽障碍提供一种潜在 的治疗方法。     

电刺激治疗对脑梗死后运动功能及星形胶质细胞活性的影响

目的　观察电刺激治疗对大鼠脑梗死后运动功能和脑星形胶质细胞活性的影响 ,方法　易卒中型肾血管性高血压大鼠 (RHRSP)右侧大脑中动脉闭塞后 ,电刺激其瘫痪肢体的 4个穴位 ,以走横木试验 (BWT)评价大鼠的精细运动功能恢复情况 ,免疫组化法观察脑星形胶质细胞活性。结果　经电刺激治疗的大鼠 ,运动功能的恢复较对照组明显改善 (P<0 0 1) ;电刺激治疗组在坏死边缘区 (A区 )和远隔区 (B)星形胶质纤维酸性蛋白 (GFAP)表达均较对照组高 ;GFAP阳性细胞浆平均光密度值变化情况与GFAP表达变化基本相同。结论　电刺激可通过增强星形胶质细胞活性而促进瘫痪肢体功能恢复。脑梗死后星形胶质细胞在其修复中起了重要的作用。     

卒中后肢体痉挛治疗的研究进展

痉挛是卒中后常见的并发症之一,严重的肢体痉挛不仅会导致关节活动度的受限、灵活性 和姿势的异常,还可引起不可逆的关节挛缩、肢体功能丧失及残疾,极大地影响着患者的生活质量, 并增加照护者的负担。目前对卒中后肢体痉挛的治疗方案仍未达成共识。近年来,痉挛治疗的药物 和非药物研究也有了一定的进展,尤其是非药物治疗手段,如采用非侵入性经颅或外周电、磁刺激技 术以及基于肌动图和肌电图的多源信息采集整合分析技术等新型康复治疗手段,在痉挛治疗过程中 表现出更加精准、有效以及可重复性高等优点。现就卒中后肢体痉挛治疗的研究进展进行综述。     

Disintegration and reorganization of cortical motor processing in two patients with cerebellar stroke

Cerebello-cerebral interaction plays a fundamental role in movement processing. Extensively studied in monkeys, Cerebello-thalamocerebral information processing is less clear in humans. Taking advantage of the tight linkage between cerebellum and cerebral motor cortex, the objective of this experiment was to gain information on cerebellar function, dysfunction and recovery by analyzing movement-related cortical potentials (MRCCs). MRCPs were recorded prior to voluntary repetitive finger movements from two cerebellar stroke patients, in the acute phase of cerebellar stroke and after clinical recovery. Ten normal subjects served as controls. The main result was a significant depression of late MRCP components over the contralateral motor cortex when patients performed index finger movements of the affected side: in the acute phase, and improvement of depressed components after clinical recovery, 8–10 months later. Topographic maps of late MRCP components showed diffusely enlarged potential fields with ataxic movements in the acute phase, and re-focused fields on follow-up. We conclude that (1) late MRCP components are particularly sensitive to cerebellar input in humans and can reflect different functional states of the cerebellum, (2) disturbance of motor cortex function after cerebellar stroke (diaschisis) can occur as a temporary phenomenon that reverses with good clinical recovery.     

Non‐invasive magnetic stimulation of the human cerebellum facilitates cortico‐bulbar projections in the swallowing motor system

Background Animal and human brain imaging studies suggest that the cerebellum plays an important role in the control of swallowing. In this study, we probed the interaction between cerebellar and pharyngeal motor cortical activity with transcranial magnetic stimulation (TMS) to determine if the cerebellum can modulate cortical swallowing motor circuitry. Methods Healthy volunteers (n = 16, eight men, mean age = 32, range 19–57 years) underwent TMS measurements of pharyngeal electromyography (EMG) recorded from a swallowed intraluminal catheter to assess cortical and cerebellar excitability. Subjects then underwent a paired pulse paradigm, where active or sham TMS conditioning pulses over the cerebellum and control sites were followed by suprathreshold TMS over the cortical pharyngeal area. Paired pulses were delivered at varying inter‐stimulus intervals (ISIs) with the cortical response amplitudes being assessed. Key Results Stimulation of the cerebellum over its midline or hemispheres evoked distinct pharyngeal EMG responses. There was no difference in EMG amplitudes following cerebellar hemispheric or midline stimulation (mean 55.5 ± 6.9 vs 42.8 ± 5.9 μV, P = 0.08). In contrast, after cerebellar preconditioning, the cortically evoked responses underwent maximal facilitation at ISIs of 50–200 ms (P < 0.05), an effect not seen with sham or trigeminal nerve preconditioning. Conclusions & Inferences Posterior fossa stimulation excites the cerebellum and evokes direct motor responses within the pharynx. When conditioned with TMS, the cerebellum strongly facilitates the cortical swallowing motor pathways. This finding suggests that the cerebellum exerts a modulatory effect on human swallowing and raises the possibility that excitatory neurostimulation of the cerebellum may be therapeutically useful in promoting recovery of dysphagia after neural damage.     

Motor representation in patients rapidly recovering after stroke: a functional magnetic resonance imaging and transcranial magnetic stimulation study

OBJECTIVE: Neuroimaging studies have suggested an evolution of the brain activation pattern in the course of motor recovery after stroke. Initially poor motor performance is correlated with an recruitment of the uninjured hemisphere that continuously vanished until a nearly normal (contralateral) activation pattern is achieved and motor performance is good. Here we were interested in the early brain activation pattern in patients who showed a good and rapid recovery after stroke. METHODS: Ten patients with first-ever ischemic stroke affecting motor areas had to perform self-paced simple or more complex movements with the affected or the unaffected hand during functional magnetic resonance imaging (fMRI). The location and number of activated voxels above threshold were determined. To study possible changes in the cortical motor output map the amplitude of the motor evoked potentials (MEP) and the extent of the excitable area were determined using transcranial magnetic stimulation (TMS). RESULTS: The pattern of activation observed with movements of the affected and the unaffected hand was similar. In the simple motor task significant (P<0.05) increases were found in the primary motor cortex ipsilateral to the movement, the supplementary motor area and the cerebellar hemisphere contralateral to the movement during performance with the affected hand compared to movements with the unaffected hand. When comparing simple with more complex movements performed with either the affected or the unaffected hand, a further tendency to increased activation in motor areas was observed. The amplitude of MEPs obtained from the affected hemisphere was smaller and the extent of cortical output maps was decreased compared to the unaffected hemisphere; but none of the patients showed MEPs at the affected hand when the ipsilateral unaffected motor cortex was stimulated. CONCLUSIONS: Despite a rapid and nearly complete motor recovery the brain activation pattern was associated with increased activity in (bilateral) motor areas as revealed with fMRI. TMS revealed impaired motor output properties, but failed to demonstrate ipsilateral motor pathways. Successful recovery in our patients may therefore rely on the increased bilateral activation of existing motor networks spared by the injury.     

In vivo transduction of murine cerebellar Purkinje cells by HIV-derived lentiviral vectors

Cerebellar Purkinje cells are key elements in motor learning and motor coordination, and therefore, it is important to clarify the mechanisms by which Purkinje cells integrate information and control cerebellar function. Gene transfer into neurons, followed by the assessment of the effects on neural function, is an effective approach for examining gene function. However, this method has not been used fully in the study of the cerebellum because adenovirus vectors, the vectors most commonly used for in vivo gene transfer, have very low affinity for Purkinje cells. In this study, we used a human immunodeficiency virus (HIV)-derived lentiviral vector and examined the transduction profile of the vector in the cerebellum. A lentiviral vector carrying the GFP gene was injected into the cerebellar cortex. Seven days after the injection, Purkinje cells were efficiently transduced without significant influence on the cell viability and synaptic functions. GFP was also expressed, though less efficiently, in other cortical interneurons and Bergmann glias. In contrast to reported findings with other viral vectors, no transduced cells were observed outside of the cerebellar cortex. Thus, when HIV-derived lentiviral vectors were injected into the cerebellar cortex, transduction was limited to the cells in the cerebellar cortex, with the highest tropism for Purkinje cells. These results suggest that HIV-derived lentiviral vectors are useful for the study of gene function in Purkinje cells as well as for application as a gene therapy tool for the treatment of diseases that affect Purkinje cells.     

Hand motor recovery after stroke: tuning the orchestra to improve hand motor function.

The motor deficits after stroke are not only the manifestation of the injured brain region, but rather the expression of the ability of the rest of the brain to maintain function. After a lesion in the primary motor cortex, parallel motor circuits might be activated to generate some alternative input to the spinal motoneurons. These parallel circuits may originate from areas such as the contralateral, undamaged primary motor area, bilateral premotor areas, bilateral supplementary motor areas, bilateral somatosensory areas, cerebellum, and basal ganglia. Most importantly, the efferent, cortico-spinal output pathways must be preserved for a desired behavioral result. Most of the recovery of function after a stroke may represent actual relearning of the skills with the injured brain. The main neural mechanisms underlying this relearning process after stroke involve shifts of distributed contributions across a specific neural network (fundamentally the network engaged in skill learning in the healthy). If these notions are indeed correct, then neuromodulatory approaches, such as transcranial magnetic stimulation, targeting these parallel circuits might be useful to limit injury and promote recovery after a stroke. This paper reviews the stroke characteristics that can predict a good recovery and compensations across brain areas that can be implemented after a stroke to accelerate motor function recovery.     

Somatosensory inputs modulate the excitability of cerebellar-cortical interaction

ObjectiveTranscranial magnetic stimulation (TMS) delivered over the cerebellum 5–7 ms prior to a stimulus over the contralateral primary motor cortex (M1) reduces the excitability of M1 output, a phenomenon termed cerebellar brain inhibition (CBI). The cerebellum receives sensory information for adaptive motor coordination and motor planning. Here, we explored through TMS whether a peripheral electrical stimulus modulates CBI.MethodsWe studied the effect of right median nerve electrical stimulation (ES) on CBI from right cerebellum (conditioning stimulus, CS) to left M1 (test stimulus, TS) in 12 healthy subjects. The following ES-CS inter-stimulus intervals (ISIs) were tested: 25, 30 and 35 ms. CS-TS ISI was set at 5 ms.ResultsWe found significantly weaker CBI when the ES was delivered 25 ms (p < 0.001) and 35 ms (p < 0.001) earlier the CS over the ipsilateral cerebellum and a trend for 30 ms ES-CS ISI (p = 0.07).ConclusionsWe hypothesize that the activation of cerebellar interneurons together with intrinsic properties of Purkinje cells may be responsible of the decreased CBI when the peripheral stimulation preceded the cerebellar stimulation of 25 and 35 ms.SignificanceTo test the interaction between somatosensory inputs and cerebello-cortical pathway may be important in a variety of motor tasks and neuropsychiatric disorders.     

A Hypothetical Universal Model of Cerebellar Function: Reconsideration of the Current Dogma

The cerebellum is commonly studied in the context of the classical eyeblink conditioning model, which attributes an adaptive motor function to cerebellar learning processes. This model of cerebellar function has quite a few shortcomings and may in fact be somewhat deficient in explaining the myriad functions attributed to the cerebellum, functions ranging from motor sequencing to emotion and cognition. The involvement of the cerebellum in these motor and non-motor functions has been demonstrated in both animals and humans in electrophysiological, behavioral, tracing, functional neuroimaging, and PET studies, as well as in clinical human case studies. A closer look at the cerebellum’s evolutionary origin provides a clue to its underlying purpose as a tool which evolved to aid predation rather than as a tool for protection. Based upon this evidence, an alternative model of cerebellar function is proposed, one which might more comprehensively account both for the cerebellum’s involvement in a myriad of motor, affective, and cognitive functions and for the relative simplicity and ubiquitous repetitiveness of its circuitry. This alternative model suggests that the cerebellum has the ability to detect coincidences of events, be they sensory, motor, affective, or cognitive in nature, and, after having learned to associate these, it can then trigger (or “mirror”) these events after having temporally adjusted their onset based on positive/negative reinforcement. The model also provides for the cerebellum’s direction of the proper and uninterrupted sequence of events resulting from this learning through the inhibition of efferent structures (as demonstrated in our lab).     

Non-invasive Cerebellar Stimulation: a Promising Approach for Stroke Recovery?

Non-invasive brain stimulation (NIBS) combined with behavioral training is a promising strategy to augment recovery after stroke. Current research efforts have been mainly focusing on primary motor cortex (M1) stimulation. However, the translation from proof-of-principle to clinical applications is not yet satisfactory. Possible reasons are the heterogeneous properties of stroke, generalization of the stimulation protocols, and hence the lack of patient stratification. One strategy to overcome these limitations could be the evaluation of alternative stimulation targets, like the cerebellum. In this regard, first studies provided evidence that non-invasive cerebellar stimulation can modulate cerebellar processing and linked behavior in healthy subjects. The cerebellum provides unique plasticity mechanisms and has vast connections to interact with neocortical areas. Moreover, the cerebellum could serve as a non-lesioned entry to the motor or cognitive system in supratentorial stroke. In the current article, we review mechanisms of plasticity in the cortico-cerebellar system after stroke, methods for non-invasive cerebellar stimulation, and possible target symptoms in stroke, like fine motor deficits, gait disturbance, or cognitive impairments, and discuss strategies for multi-focal stimulation.     

Bone marrow derived mesenchymal stem cell transplantation in cerebellar degeneration: a behavioral study

In addition to its key role in complex motor function, the cerebellum is increasingly recognized to have a role in cognition. Thus, motor and cognitive deficits can be associated with cerebellar degeneration. After unilateral lesion in cerebellum (folia VI) was caused by Quinolinic acid, CM-DiI labeled mesenchymal stem cells (MSCs), which were isolated and purified from bone marrow, were transplanted into the damaged folium. Motor function was assessed using the cylinder test, rotarod, hanging wire and beam balance during 6 weeks after transplantation. Cognitive function was assessed using the Morris water maze learning paradigm in 3 weeks after transplantation. Six weeks after transplantation surviving MSCs were detectable in QA-treated animals. The MSC-transplanted group showed markedly improved functional performance in spatial memory, motor learning, locomotor asymmetry, dysmetria, abnormality in neuromuscular strength and equilibrium 2-6 weeks compared with the controls. We found that cerebellar lesions produced deficits (folia VI) in motor and cognitive aspects of a spatial task. The results indicate that transplantation of MSCs can significantly reduce the behavioral abnormalities of these animals during six weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow derived adult stem cells promises for treatment of cerebellar diseases.     

Effects on motor learning of transcranial alternating current stimulation applied over the primary motor cortex and cerebellar hemisphere

Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation that modulates oscillatory neural activity in the cortical area under the electrodes. Gamma (γ)-tACS applied over the primary motor cortex (M1) and cerebellar hemisphere is known to improve motor performance; however, it is not yet known whether it affects motor learning. Thus, here we investigated whether γ-tACS applied over the M1 and cerebellar hemisphere affects motor learning. This study involved 30 healthy subjects (14 females, 16 males) performing a visuomotor control task (eight trials) during an administration of either γ-tACS or a sham stimulation (15 subjects per condition) over their right M1 and left cerebellar hemisphere. Each subject performed five trials after 24 h. The motor learning efficiency, motor learning retention and re-motor learning efficiency in each condition were compared. The motor learning retention in the γ-tACS condition was significantly higher than that in the sham condition (p = 0.031). Thus, subjects who were administered γ-tACS maintained their motor performance the next day better than sham-stimulated subjects. There was no significant difference between the conditions in the motor learning efficiency and those in the re-motor learning efficiency. Our results demonstrate that γ-tACS administered over the M1 and cerebellar hemisphere during a motor learning task can enhance motor learning retention.