Modulating brain plasticity in rehabilitation of stroke and other brain lesions

背景： 中风和创伤性脑损伤导致的残疾是成人长期并发症的主要原因。目前还没有普遍接受的治疗方法来治疗这些疾病，这些残疾造成的经济、个人、家庭和社会代价不可低估。来自不同实验室的初步数据表明，通过药理学、脑刺激和体感刺激技术来调节受损大脑的可塑性过程是可能的。本项目的目的是确定卒中运动障碍的机制，并描述最有希望改善这些患者皮质可塑性以促进功能恢复的技术。 今年的调查结果： 我们回顾了使用TMS和TDCs来影响刺激位置下的局部神经活动以及整个大脑的远程互联网络活动的策略。 大多数中风康复研究都是在高收入国家进行的。一项研究的目的是确定在巴西进行的一项研究方案中患者纳入的主要障碍。我们在中风康复的先导性、随机、双盲临床试验中评估了排除患者的原因。进行描述性统计分析，报告571名筛查患者中只有5.6%纳入其中。复发性卒中导致45.4%的潜在符合条件的患者被排除。我们得出结论，复发性卒中是纳入该方案患者的一大障碍。康复试验的外部有效性将受益于根据患者的地区性特征定义研究标准，包括中风复发的比率。 在一项研究中，我们报告了在非偏瘫手臂用力过程中，针对同侧初级运动皮质(M1)的大脑半球间抑制的变化。在相同情况下，年龄匹配的健康对照组从活动期到静止期M1的抑制率显著高于卒中患者从活动期对照到静止期自身M1的增加。在偏瘫手臂功能的9孔定位试验中，对侧抑制增加较多的患者表现更好。我们的发现表明，用非瘫痪的手臂产生力量并不一定过度抑制瘫痪的手臂。尽管我们的研究因样本量小而限制了泛化，但我们发现，在这一亚组慢性卒中患者中，较大的主动对照对静息自身M1的抑制与较好的康复相关。 在一项关于脑机接口的研究中，我们与德国的一个研究小组合作，发现上肢(结合手和改良手臂)Fugl-Meyer评估(CFMA)运动评分存在显著的群体时间交互作用。治疗组治疗后CFMA评分的改善明显优于对照组(P=0.018)，表现为明显改善(相差0.563分，P=0.018)，反映了瘫痪肌肉由无活动变为部分活动的临床意义。实验组CFMA的改善与fMRI偏侧指数的变化和瘫痪的手部肌电活动相关。安慰剂预期得分在两组中是相似的。我们的结论是，在行为定向理疗的基础上增加BMI训练，可以在没有残留手指运动的慢性中风患者中诱导运动功能的改善，并可能为中风神经康复打开一扇新的大门。

Background: Disability resulting from stroke and traumatic brain injury represent the main causes of long-term complications in adults. There are no universally accepted treatments available to treat these conditions and the financial, personal, familial and social cost of these disabilities cannot be underestimated. Preliminary data from different laboratories have shown that it is possible to modulate plastic processes in the lesioned brain by pharmacological, brain stimulation and somatosensory stimulation techniques. The purpose of this project is to identify mechanisms of stroke motor disability and characterize the most promising techniques to improve cortical plasticity in these patients to enhance functional recovery. Findings this year: We reviewed strategies using TMS and tDCS to influence regional neural activity underlying the stimulation location and also distant interconnected network activity throughout the brain. Most stroke rehabilitation studies have been performed in high-income countries. The aim of one study was to identify the main barriers for patient inclusion in a research protocol performed in Brazil. We evaluated reasons for exclusion of patients in a pilot, randomized, double-blinded clinical trial of stroke rehabilitation. Descriptive statistical analysis was performed and report that only 5.6% of 571 screened patients were included. Recurrent stroke was responsible for exclusion of 45.4% of potentially eligible patients We concluded that recurrent stroke represented a big barrier to enroll patients in the protocol. External validity of rehabilitation trials will benefit from definition of study criteria according to regional characteristics of patients, including rates of recurrent stroke. In one study we report changes in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario. Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic post stroke. In one study on brain-computer interface, in collaboration with a group in Germany, we found a significant group time interaction in upper limb (combined hand and modified arm) Fugl-Meyer assessment (cFMA) motor scores. cFMA scores improved more in the experimental than in the control group, presenting a significant improvement of cFMA scores (3.41 0.563-point difference, p = 0.018) reflecting a clinically meaningful change from no activity to some in paretic muscles. cFMA improvements in the experimental group correlated with changes in fMRI laterality index and with paretic hand electromyography activity. Placebo-expectancy scores were comparable for both groups. We concluded that the addition of BMI training to behaviorally oriented physiotherapy can be used to induce functional improvements in motor function in chronic stroke patients without residual finger movements and may open a new door in stroke neurorehabilitation.