Motor recovery following stroke: a transcranial magnetic stimulation study.

OBJECTIVES: To verify the usefulness of early recording of motor evoked potentials (MEPs) in predicting motor outcome after stroke and to investigate the neural mechanisms underlying functional recovery following stroke. METHODS: We performed a comparative analysis of the behaviour of motor responses evoked by transcranial magnetic stimulation (TMS) of the ipsilateral and contralateral motor cortex in the affected and unaffected thenar muscles of 21 consecutive patients with acute stroke. RESULTS: According to the behaviour of MEPs in the affected muscles, patients could be divided into 3 groups: (a) 10 subjects with absent responses to TMS of both the damaged and undamaged hemisphere, whose motor recovery was poor and related to the size of MEPs on the normal side; (b) 5 subjects with larger MEPs upon TMS of the ipsilateral (undamaged) than of the contralateral (damaged) cortex, whose good recovery possibly resulted from the emergence of ipsilateral pathways; (c) 6 subjects with larger MEPs in the affected than in the unaffected muscles, whose good recovery was possibly subserved by alternative circuits taking over cortical deafferentation. CONCLUSIONS: Early MEP recording in acute stroke provides useful information on the clinical prognosis and the different mechanisms of motor recovery.     

Plasticity of the human motor system following muscle reconstruction: a magnetic stimulation and functional magnetic resonance imaging study

OBJECTIVE: Although motor system plasticity in response to neuromuscular injury has been documented, few studies have examined recovered and functioning muscles in the human. We examined brain changes in a group of patients who had a muscle transfer. METHODS: Transcranial magnetic stimulation (TMS) was used to study a unique group of 9 patients who had upper extremity motor function restored using microneurovascular transfer of the gracilis muscle. The findings from the reconstructed muscle were compared to the homologous muscle of the intact arm. One patient was also studied with functional magnetic resonance imaging (fMRI). RESULTS: TMS showed that the motor threshold and short interval intracortical inhibition was reduced on the transplanted side while at rest but not during muscle activation. The difference in motor threshold decreased with the time since surgery. TMS mapping showed no significant difference in the location and size of the representation of the reconstructed muscle in the motor cortex compared to the intact side. In one patient with reconstructed biceps muscle innervated by the intercostal nerves, both TMS mapping and fMRI showed that the upper limb area rather than the trunk area of the motor cortex controlled the reconstructed muscle. CONCLUSIONS: Plasticity occurs in cortical areas projecting to functionally relevant muscles. Changes in the neuronal level are not necessarily accompanied by changes in motor representation. Brain reorganization may involve multiple processes mediated by different mechanisms and continues to evolve long after the initial injury. SIGNIFICANCE: Central nervous system plasticity following neuromuscular injury may have functional relevance.     

磁共振成像应用于经颅磁刺激抗抑郁治疗的靶点定位和疗效预测的研究进展

抑郁症是一种病程长且易反复发作的心境障碍。经颅磁刺激作为一种无创的非侵入性抗抑郁治疗手段,其疗效和安全性已得到充分证实,但由于无法精确进行治疗靶点定位和疗效预测等问题,仍存在一定局限性。目前磁共振成像应用于经颅磁刺激治疗抑郁症的靶点定位和疗效预测的研究越来越多,本文中旨在整理相关研究,总结该技术的应用进展。     

功能性电刺激结合重复经颅磁刺激用于缺血性脑卒中偏瘫患者步行障碍恢复的临床观察

目的 观察功能性电刺激结合重复经颅磁刺激用于缺血性脑卒中偏瘫患者步行障碍恢复的临床疗效。方法 将53例缺血性脑卒中偏瘫患者随机分为对照组、治疗组、假治疗组3组,在均接受常规康复训练的基础上对照组接受功能性电刺激治疗,治疗组接受功能性电刺激及重复经颅磁刺激治疗,假治疗组接受功能性电刺激及假重复经颅磁刺激治疗; 治疗前及治疗8周后采用步态运动学参数、时间参数、距离参数及Amer-Lindholm分级对3组患者的下肢综合运动功能进行评定。结果 治疗前3组患者步态运动学参数、时间参数、距离参数及Amer-Lindholm分级评分均无显著差异(P>0.05),治疗8周后3组患者上述指标明显改善且治疗组改善幅度明显优于其余2组(P<0.05)。结论 功能性电刺激联合重复经颅磁刺激治疗有利于改善缺血性脑卒中偏瘫患者的步行运动功能。     

脑血管病患者经颅磁刺激运动诱发电位的研究

采用经颅磁刺激运动诱发电位（ＭＥＰ）对７２例脑血管病（ＣＶＤ）患者和５０例正常人进行检测。结果：ＣＶＤ患者瘫痪侧上肢磁刺激无反应或皮层潜伏期和中枢传导时间（ＣＭＣＴ）较正常对照组和健侧显著延长（Ｐ＜０．００１）；瘫痪侧下肢磁刺激无反应或ＣＭＣＴ较正常对照组和健侧显著延长（Ｐ＜０．０５）。脑出血与脑梗塞患者ＭＥＰ异常率无显著差异（Ｐ＞０．０５），而与临床病情轻重和病变部位密切相关。提示ＭＥＰ能客观反映ＣＶＤ患者中枢运动传导通路功能受损的情况。     

重复经颅磁刺激对抑郁症患者磁共振波谱和疗效的影响

目的 探讨重复经颅磁刺激(rTMS)治疗抑郁症患者的疗效及可能机制. 方法 选择自2012年8月至2014年7月在全军精神疾病防治研究所住院的抑郁症患者70例,所有患者均符合美国精神障碍诊断与统计手册第4版诊断标准.按照随机数字表法将患者随机分为研究组(n=36)和对照组(n=34),2组患者均接受盐酸文拉法辛缓释片(75 mg/片)治疗.研究组同时联合10Hz rTMS作用于左侧背外侧前额叶(DLPFC)治疗4周,对照组给予rTMS伪刺激.治疗前后采用多体素磁共振质子波谱(1H-MRS)检测患者前额叶和丘脑N-乙酰基天门冬氨酸(NAA)、胆碱复合物(Cho)与肌酸复合物(Cr)含量.采用汉密尔顿抑郁量表(HAMD)于治疗前、治疗4周评估临床症状和疗效. 结果 (1)研究组治疗前左侧前额叶、左侧丘脑NAA/Cr值分别为1.51±0.34、1.36±0.29,治疗后分别升高至1.71±0.42、1.54±0.34,差异有统计学意义(P＜0.05).对照组双侧前额叶、双侧丘脑的NAA/Cr值、Cho/Cr值治疗前后差异均无统计学意义(P＞0.05).(2)研究组、对照组治疗前HAMD评分分别为32.3±8.8、31.8±8.5,治疗后降低为12.3±4.7、15.2±5.0,差异均有统计学意义(P＜0.05).研究组治疗前后的HAMD评分差值大于对照组,差异有统计学意义(P＜0.05).(3)治疗后,研究组显效率为80.6％(29/36)、治愈率为27.8％(10/36),对照组显效率为50.0％(17/34)、治愈率为5.9％(2/34),2组间显效率和治愈率的差异均有统计学意义(P＜0.05).(4)研究组盐酸文拉法辛缓释片平均治疗剂量为(136.6±28.4)mg/d、最大剂量为(175.0±35.6)mg/d;对照组平均治疗剂量为(162.4±32.2)mg/d、最大剂量为(216.2±40.3)mg/d;组间差异均有统计学意义(P＜0.05). 结论 10 Hz rTMS联合盐酸文拉法辛缓释片可以调节抑郁症患者前额叶和丘脑的神经生化代谢,进而改善抑郁症状,降低抗抑郁药物使用剂量.     

Combining transcranial magnetic stimulation and functional imaging in cognitive brain research: possibilities and limitations

Transcranial magnetic stimulation (TMS) is a widely used tool for the non-invasive study of basic neurophysiological processes and the relationship between brain and behavior. We review the physical and physiological background of TMS and discuss the large body of perceptual and cognitive studies, mainly in the visual domain, that have been performed with TMS in the past 15 years. We compare TMS with other neurophysiological and neuropsychological research tools and propose that TMS, compared with the classical neuropsychological lesion studies, can make its own unique contribution. As the main focus of this review, we describe the different approaches of combining TMS with functional neuroimaging techniques. We also discuss important shortcomings of TMS, especially the limited knowledge concerning its physiological effects, which often make the interpretation of TMS results ambiguous. We conclude with a critical analysis of the resulting conceptual and methodological limitations that the investigation of functional brain–behavior relationships still has to face. We argue that while some of the methodological limitations of TMS applied alone can be overcome by combination with functional neuroimaging, others will persist until its physical and physiological effects can be controlled.     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation

Summary Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.     

功能磁共振成像在植物状态研究中的应用

一、植物状态及其研究历程随着现代医疗技术的进步,危重患者的死亡率明显降低,临床上可以见到越来越多的意识障碍患者.1972年由Jennett和Plum在Lancet上首次提出持续性植物状态(vegetative state,VS)的概念,用以取代当时混杂应用的各类名词,如极深度昏迷,运动不能性缄默,永久性、不可逆性或稽延性昏迷、去大脑或去皮层状态等,这一见解以后逐渐为各国学者所采纳.1994年美国PVS多学科专责小组对VS下的定义为:“患者完全失去对自身及周围环境的认知,有睡眠一觉醒周期,下丘脑及脑干的自主功能完全或部分保存”.此类患者死亡率高,致残严重且缺乏有效治疗,给社会及家庭造成沉重的负担,引起了医学界和全社会的广泛关注.     

Repetitive transcranial magnetic stimulation of language function in patients with refractory epilepsy A preliminary functional magnetic resonance imaging study

To investigate whether repetitive transcranial magnetic stimulation （rTMS） can improve language function in patients with refractory epilepsy, three right-handed, refractory epilepsy patients who had complained of language dysfunction, were recruited. Over 1 month, 1-Hz rTMS treatment was performed every 3 days. A battery of language production and functional MRI were evaluated in the patients using a standard verb generation task both before and 1 month after rTMS treatment. Significant and lasting improvement in verb production was observed following rTMS treatment. Functional MRI results revealed that the left frontal lobes of two patients were more activated than they had been prior to therapy, and activation was primarily concentrated in the language-related areas. Results demonstrated that low frequency rTMS has potential to improve language function in patients with refractory epilepsy.     

Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study

Functional MRI (fMRI), visualizing changes in cerebral blood oxygenation, has to date not been performed either in patients with writer's cramp or in healthy subjects during writing. We compared the cerebral and cerebellar activation pattern of 12 patients with writer's cramp during writing with a group of 10 healthy subjects performing the same tasks over 30-s periods of rest or writing. Sixty echo planar imaging multi-slice datasets were analysed using SPM96 software. Data were analysed for each subject individually and groupwise for patients vs. controls. Healthy subjects showed a significant activation of the ipsilateral dentate nucleus, contralateral cerebellar hemisphere, contralateral primary sensorimotor cortex, and contralateral precentral gyrus during writing. Patients with writer's cramp showed significantly greater activation of the ipsilateral cerebellar hemisphere than controls. Also the activation in the primary sensorimotor cortex extended further caudally and anteriorly towards the premotor association area. Activation was observed in the thalamus during writing only among the patients. Our results indicate an increased basal ganglia output via the thalamus to the motor and premotor cortical areas in dystonia patients and support the notion of disinhibition of the motor cortex leading to coconcentrations and dystonic postures. Received: 10 November 1999 / Received in revised form: 4 April 2000 / Accepted: 26 April 2000     

Proton magnetic resonance spectroscopy and transcranial magnetic stimulation for the detection of upper motor neuron degeneration in ALS patients

Transcranial magnetic stimulation (TMS) was compared to proton magnetic resonance spectroscopy (¹H-MRS) for the detection of upper motor neuron loss or dysfunction in 49 ALS patients classified according to the El Escorial criteria. Abnormal NAA/Cho ratios were detected in 53% of ALS patients. Abnormal TMS results (i.e. cortical inexcitability or prolonged CMCT's) were obtained in 63% of ALS patients. If one or both methods were considered for diagnosis of upper motor neuron degeneration/dysfunction, the percentage of abnormal findings was 77%, whilst in 39% of all patients both methods produced abnormal results. Compared to TMS, ¹H-MRS detected more patients with upper motor neuron involvement in the suspected El Escorial subgroup (42% versus 25%), whereas TMS detected more patients with upper motor neuron involvement in the possible (81% versus 50%), probable (71% versus 57%) and definite El Escorial subgroup (71% versus 64%). We conclude that the combined use of ¹H-MRS and TMS increases diagnostic accuracy for the detection of upper motor neuron involvement in ALS patients.     

Blunted activation in orbitofrontal cortex during mania: a functional magnetic resonance imaging study.

BACKGROUND: Patients with bipolar disorder have been reported to have abnormal cortical function during mania. In this study, we sought to investigate neural activity in the frontal lobe during mania, using functional magnetic resonance imaging (fMRI). Specifically, we sought to evaluate activation in the lateral orbitofrontal cortex, a brain region that is normally activated during activities that require response inhibition. METHODS: Eleven manic subjects and 13 control subjects underwent fMRI while performing the Go-NoGo task, a neuropsychological paradigm known to activate the orbitofrontal cortex in normal subjects. Patterns of whole-brain activation during fMRI scanning were determined with statistical parametric mapping. Contrasts were made for each subject for the NoGo minus Go conditions. Contrasts were used in a second-level analysis with subject as a random factor. RESULTS: Functional MRI data revealed robust activation of the right orbitofrontal cortex (Brodmann's area [BA] 47) in control subjects but not in manic subjects. Random-effects analyses demonstrated significantly less magnitude in signal intensity in the right lateral orbitofrontal cortex (BA 47), right hippocampus, and left cingulate (BA 24) in manic compared with control subjects. CONCLUSIONS: Mania is associated with a significant attenuation of task-related activation of right lateral orbitofrontal function. This lack of activation of a brain region that is usually involved in suppression of responses might account for some of the disinhibition seen in mania. In addition, hippocampal and cingulate activation seem to be decreased. The relationship between this reduced function and the symptoms of mania remain to be further explored.     

The role of the intact hemisphere in recovery of midline muscles after recent monohemispheric stroke

Transcranial magnetic stimulation (TMS) of the motor cortex was used to study basic mechanisms of motor reorganization after major hemispheric stroke in humans. We sought to clarify the possible role of the intact hemisphere in motor recovery of the lingual muscles, and to evaluate the compensatory use of preexisting uncrossed motor pathways projecting to these midline muscles. TMS and bilateral surface recordings from the lingual muscles were carried out in six selected stroke patients who presented with a unilateral lingual paralysis after a limited monohemispheric ischemia. The first examination was performed during the symptomatic stage (t ₁) and was repeated after complete recovery of lingual function had been established (t ₂). The cortical motor output patterns were analyzed and compared with the data from 40 healthy controls. In the controls TMS of either hemisphere invariably produced contralateral and ipsilateral compound muscle action potentials (CMAPs), elicited through crossed and uncrossed central motor pathways, respectively. In most individuals an asymmetric cortical motor output pattern was found, as significantly greater mean CMAPs of shorter onset latencies were recorded from the contralateral lingual muscles than from the ipsilateral responses. In the six patients with a unilateral lingual paralysis a similar pattern was found on initial examination by stimulating the intact hemisphere, whereas TMS of the affected hemisphere failed to elicit any CMAP bilaterally. At t ₂ all patients had regained normal lingual function. Only one patient showed evidence of a complete recovery of the primarily affected hemisphere, as TMS now elicited normal CMAPs bilaterally. In the remaining five patients the unilateral interruption of the corticonuclear pathways persisted in spite of complete functional recovery. In these subjects the recovery of symmetric lingual movements must be attributed to the intact hemisphere. From this it is concluded that recovery of a unilateral lingual paralysis after restricted monohemispheric lesions is possible without recovery of the cortical motor projections from the affected hemisphere. In these cases the intact hemisphere is responsible for restoration of normal lingual movements, most likely by potentiating the effect of preexisting uncrossed motor pathways. Received: 26 March 1998 Accepted: 24 June 1998     

Motor cortex plasticity during forced-use therapy in stroke patients: a preliminary study

Treatment-induced plastic changes were investigated in the brains of stroke patients in the subacute stage of illness. Nine patients participated in 1 week of conventional physiotherapy. In the subsequent week conventional physiotherapy was combined with forced-use therapy. Focal transcranial magnetic stimulation was used to determine the motor output areas of the abductor pollicis brevis muscles prior to the treatment and after the first and after the second week. Motor performance was evaluated using the Nine Hole Peg Test, the Frenchay Arm Test and vigorometry to measure the grip strength. Before treatment the cortical representation area of the paretic hand muscle was significantly smaller than the contralateral side. This difference persisted after the first week of physiotherapy. In contrast, the motor output map in the affected hemisphere was significantly enlarged after forced-use therapy. This increase in motor cortex excitability was accompanied by a significant improvement in dexterity. Across the two treatment weeks the centres of the motor output maps shifted significantly stronger in the affected hemisphere than in unaffected hemisphere, suggesting the recruitment of adjacent brain areas. We conclude that the combination of forced-use therapy and conventional physiotherapy enhances motor cortex excitability and improves motor performance compared to a preceding conventional physiotherapy alone. Due to the small number of patients and the lack of a control group, these results are preliminary observations and require replication in a larger sample. Received: 2 February 2000, Received in revised form: 22 June 2000, Accepted: 20 November 2000     

低频重复经颅磁刺激联合以任务为导向作业疗法对脑卒中患者上肢运动功能的康复作用

目的探讨低频重复经颅磁刺激联合以任务为导向作业疗法对脑卒中患者上肢运动功能的康复作用。方法共42例脑卒中后偏瘫患者随机接受常规康复训练和以任务为导向作业疗法(对照组,20例)以及在此基础上联合健侧运动皮质低频(1 Hz)重复经颅磁刺激(治疗组,22例),分别于治疗前、治疗4周时和治疗后3个月采用Fugl-Meyer上肢评价量表(FMA-UE)和Wolf运动功能测验(WMFT)评价上肢运动功能,记录并分析健侧运动皮质运动诱发电位潜伏期和中枢运动传导时间。结果与对照组相比,治疗组FMA-UE评分(P=0.006)和WMFT评分(P=0.024)均增加;两组不同时间点FMA-UE评分(P=0.000)和WMFT评分(P=0.000)差异有统计学意义,其中治疗4周时和治疗后3个月FMA-UE评分(均P=0.000)和WMFT评分(均P=0.000)均高于治疗前,治疗后3个月FMA-UE评分(均P=0.000)和WMFT评分(均P=0.000)亦高于治疗4周时。两组患者治疗前后健侧运动皮质运动诱发电位潜伏期(P=0.979)和中枢运动传导时间(P=0.807)差异无统计学意义,不同时间点(治疗前、治疗4周时和治疗后3个月)健侧运动皮质运动诱发电位潜伏期(P=0.085)和中枢运动传导时间(P=0.507)差异亦无统计学意义。结论脑卒中患者健侧运动皮质低频重复经颅磁刺激联合以任务为导向作业疗法可以有效改善脑卒中患者上肢运动功能,值得临床推广应用。     

Publication trends in transcranial magnetic stimulation: a 30-year panorama

Background

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has broad diagnostic and therapeutic potential across a range of neurological and psychiatric diseases.

Presurgical language mapping in children with epilepsy: clinical usefulness of functional magnetic resonance imaging for the planning of cortical stimulation

Purpose: Presurgical language mapping in dominant hemisphere epilepsy to evaluate the risk of postoperative deficit is particularly difficult in children. Extraoperative invasive cortical stimulation can show some areas critical to language, but not all of them, due to scarce sampling, poor cooperation, cortical immaturity, or network reorganization, whereas functional magnetic resonance imaging (fMRI) displays entire networks involved in, but not necessarily critical to, language. In a homogeneous series of children with epilepsy, we compared the contributions of language fMRI and depth electrode stimulations to optimize language mapping. Methods: Eight children (7.5–15.5 years) with left frontal or temporal epilepsy underwent language fMRI and language stimulation with depth electrodes as part of their comprehensive presurgical workup. fMRI data collected during sentence generation were analyzed using statistical parametric mapping (SPM2) (false discovery rate [FDR] p < 0.05). Bipolar stimulations were performed during language production tasks. By coregistering fMRI and postimplantation computed tomography (CT) images, we were able to directly compare the cortical areas identified by both investigations. Key Findings: fMRI during sentence generation robustly showed activation in the whole perisylvian regions with little reorganization (left hemisphere dominant in 7). Of the 184 electrode contacts tested for language, only 8 were positive (language disruption) in three of the seven patients with periictal language impairment and left language dominance. All of the positive contacts colocalized with an fMRI activated cluster, that is, fMRI did not miss any region critical to language (sensitivity = 100%). However, 54 of the 176 negative contacts were within activated clusters (low specificity). Significance: In children with epilepsy, the sensitivity of fMRI during sentence generation allows for the detection of all critical regions displayed by cortical stimulation within the large perisylvian language network, but with a low specificity. It is, therefore, useful to optimize the placement of intracranial electrodes when language mapping is necessary. Systematic planning of the electrode placement according to language fMRI maps should increase the yield of extraoperative cortical stimulation, which appears rather low in children when compared to adults.     

Tactile-visual integration in the posterior parietal cortex: a functional magnetic resonance imaging study

To explore the neural substrates of visual-tactile crossmodal integration during motion direction discrimination, we conducted functional magnetic resonance imaging with 15 subjects. We initially performed independent unimodal visual and tactile experiments involving motion direction matching tasks. Visual motion discrimination activated the occipital cortex bilaterally, extending to the posterior portion of the superior parietal lobule, and the dorsal and ventral premotor cortex. Tactile motion direction discrimination activated the bilateral parieto-premotor cortices. The left superior parietal lobule, intraparietal sulcus, bilateral premotor cortices and right cerebellum were activated during both visual and tactile motion discrimination. Tactile discrimination deactivated the visual cortex including the middle temporal/V5 area. To identify the crossmodal interference of the neural activities in both the unimodal and the multimodal areas, tactile and visual crossmodal experiments with event-related designs were also performed by the same subjects who performed crossmodal tactile-visual tasks or intramodal tactile-tactile and visual-visual matching tasks within the same session. The activities detected during intramodal tasks in the visual regions (including the middle temporal/V5 area) and the tactile regions were suppressed during crossmodal conditions compared with intramodal conditions. Within the polymodal areas, the left superior parietal lobule and the premotor areas were activated by crossmodal tasks. The left superior parietal lobule was more prominently activated under congruent event conditions than under incongruent conditions. These findings suggest that a reciprocal and competitive association between the unimodal and polymodal areas underlies the interaction between motion direction-related signals received simultaneously from different sensory modalities.