卒中后运动神经反馈康复训练研究进展与前景

脑卒中(stroke)是脑区突发血管病变引起局部功能障碍的综合病症,亦是全世界第一致残类恶性神经系统疾病。运动康复训练对卒中后的功能恢复起十分重要作用,其关键在于通过肢体运动,诱发促进脑区受害神经组织产生可塑性改变,以实现运动功能的改善和恢复。但传统的被动重复训练无法调动患者的参与度和积极性,严重影响康复效果。近年来兴起基于运动想象脑-机接口(MI-BCI)的运动神经反馈康复训练模式,可由患者的主观运动意图内源性地驱动相应脑区神经来产生可塑性变化,通过大脑神经功能重组来促进肢体运动康复。评述本体感觉、视觉反馈等不同运动神经反馈模式在卒中康复训练中的应用研究进展,讨论目前MI-BCI神经反馈康复训练系统存在问题及解决对策,并预期未来的发展前景。     

New modalities of brain stimulation for stroke rehabilitation

Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation.     

A robotic system to train activities of daily living in a virtual environment

In the past decade, several arm rehabilitation robots have been developed to assist neurological patients during therapy. Early devices were limited in their number of degrees of freedom and range of motion, whereas newer robots such as the ARMin robot can support the entire arm. Often, these devices are combined with virtual environments to integrate motivating game-like scenarios. Several studies have shown a positive effect of game-playing on therapy outcome by increasing motivation. In addition, we assume that practicing highly functional movements can further enhance therapy outcome by facilitating the transfer of motor abilities acquired in therapy to daily life. Therefore, we present a rehabilitation system that enables the training of activities of daily living (ADL) with the support of an assistive robot. Important ADL tasks have been identified and implemented in a virtual environment. A patient-cooperative control strategy with adaptable freedom in timing and space was developed to assist the patient during the task. The technical feasibility and usability of the system was evaluated with seven healthy subjects and three chronic stroke patients.     

Chronic stroke recovery after combined BCI training and physiotherapy: A case report

A case of partial recovery after stroke and its associated brain reorganization in a chronic patient after combined brain computer interface (BCI) training and physiotherapy is presented. A multimodal neuroimaging approach based on fMRI and diffusion tensor imaging was used to investigate plasticity of the brain motor system in parallel with longitudinal clinical assessments. A convergent association between functional and structural data in the ipsilesional premotor areas was observed. As a proof of concept investigation, these results encourage further research on a specific role of BCI on brain plasticity and recovery after stroke.     

Performance Assessment of a Brain–Computer Interface Driven Hand Orthosis

Stroke survivors are typically affected by hand motor impairment. Despite intensive rehabilitation and spontaneous recovery, improvements typically plateau a year after a stroke. Therefore, novel approaches capable of restoring or augmenting lost motor behaviors are needed. Brain–computer interfaces (BCIs) may offer one such approach by using neurophysiological activity underlying hand movements to control an upper extremity orthosis. To test the performance of such a system, we developed an electroencephalogram-based BCI controlled electrically actuated hand orthosis. Six able-bodied participants voluntarily grasped/relaxed one hand to elicit BCI-mediated closing/opening of the orthosis mounted on the opposite hand. Following a short training/calibration procedure, participants demonstrated real-time, online control of the orthosis by following computer cues. Their performances resulted in an average of 1.15 (standard deviation: 0.85) false alarms and 0.22 (0.36) omissions per minute. Analysis of signals from electrogoniometers mounted on both hands revealed an average correlation between voluntary and BCI-mediated movements of 0.58 (0.13), with all but one online performance being statistically significant. This suggests that a BCI driven hand orthosis is feasible, and therefore should be tested in stroke individuals with hand weakness. If proven viable, this technology may provide a novel approach to the neuro-rehabilitation of hand function after stroke.     

Arm movement maps evoked by cortical magnetic stimulation in a robotic environment

Many neurological diseases result in a severe inability to reach for which there is no proven therapy. Promising new interventions to address reaching rehabilitation using robotic training devices are currently under investigation in clinical trials but the neural mechanisms that underlie these interventions are not understood. Transcranial magnetic stimulation (TMS) may be used to probe such mechanisms quickly and non-invasively, by mapping muscle and movement representations in the primary motor cortex (M1). Here we investigate movement maps in healthy young subjects at rest using TMS in the robotic environment, with the goal of determining the range of TMS accessible movements, as a starting point for the study of cortical plasticity in combination with robotic therapy. We systematically stimulated the left motor cortex of 14 normal volunteers while the right hand and forearm rested in the cradle of a two degree-of-freedom planar rehabilitation robot (IMT). Maps were created by applying 10 stimuli at each of nine locations (3×3 cm² grid) centered on the M1 movement hotspot for each subject, defined as the stimulation location that elicited robot cradle movements of the greatest distance. TMS-evoked movement kinematics were measured by the robotic encoders and ranged in magnitude from 0 to 3 cm. Movement maps varied by subject and by location within a subject. However, movements were very consistent within a single stimulation location for a given subject. Movement vectors remained relatively constant (limited to <90° section of the planar field) within some subjects across the entire map, while others covered a wider range of directions. This may be due to individual differences in cortical physiology or anatomy, resulting in a practical limit to the areas that are TMS-accessible. This study provides a baseline inventory of possible TMS-evoked arm movements in the robotic reaching trainer, and thus may provide a real-time, non-invasive platform for neurophysiology based evaluation and therapy in motor rehabilitation settings.     

Serial evaluation of patients with brain tumors using volume MRI and 3D 1H MRSI.

Patients with brain tumors are routinely monitored for tumor progression and response to therapy using magnetic resonance imaging (MRI). Although serial changes in gadolinium enhancing lesions provide valuable information for making treatment decisions, they do not address the fate of non-enhancing lesions and are unable to distinguish treatment induced necrosis from residual or recurrent tumor. The introduction of a non-invasive methodology, which could identify an active tumor more reliably, would have a major impact upon patient care and evaluation of new therapies. There is now compelling evidence that magnetic resonance spectroscopic imaging (MRSI) can provide such information as an add-on to a conventional MRI examination. We discuss data acquisition and analysis procedures which are required to perform such serial MRI-MRSI examinations and compare their results with data from histology, contrast enhanced MRI, MR cerebral blood volume imaging and FDG-PET. Applications to the serial assessment of response to therapy are illustrated by considering populations of patients being treated with brachytherapy and gamma knife radiosurgery.     

Remapping of the somatosensory cortex after a photothrombotic stroke: dynamics of the compensatory reorganization

Although stroke can affect cerebral structure and function, the brain has a potential for plasticity thanks to which some degree of function can be restored. The pathways of such recovery are of great interest, since the dynamics of rewiring of the injured brain may become the basis for designing appropriate strategies of rehabilitation. We investigated the spontaneous plasticity of cortical somatosensory representations following a focal unilateral stroke in the barrel cortex of rats. Ischemic lesions were produced with the photothrombotic technique in the cortical representation of vibrissae. Functional activation of the brain in response to the stimulation of vibrissae with destroyed cortical representation was monitored through the 2 months post-stroke survival period with [¹⁴C] 2-deoxyglucose (2DG) autoradiographic brain mapping (1, 7, 28, 56 days after the stroke). 2DG uptake was measured on autoradiograms of tangential sections in several regions of somatosensory cortex and in motor, auditory and prefrontal cortex. Behavioral deficit was assessed by the gap-crossing test 3, 28, 56 days after the stroke. Changes in the activation pattern of the intact hemisphere and non-vibrissal somatosensory representations of the lesioned hemisphere evolved during the observation period. Full recovery of the behavioral function was reached 2 months after the stroke and at the same time, new foci of activation were observed in the lesioned hemisphere. At that time, hyperactivation of the somatosensory areas in the intact hemisphere subsided. The new activation foci located in representations of anterior vibrissae, front paw and hind paw were specific for the vibrissae stimulation and were most probably a new functional representation of the vibrissae. We demonstrated spatial and temporal remodeling of the brain induced by cortical stroke, leading to vicariation of function.     

Neurorehabilitation with new functional electrical stimulation for hemiparetic upper extremity in stroke patients.

In recent years, our understanding of motor learning, neuroplasticity, and functional recovery after the occurrence of brain lesion has grown significantly. New findings in basic neuroscience have stimulated research in motor rehabilitation. Repeated motor practice and motor activity in a real-world environment have been identified in several prospective studies as favorable for motor recovery in stroke patients. Electrical stimulation can be applied in a variety of ways to the hemiparetic upper extremity following stroke. In this paper, an overview of current research into clinical and therapeutic applications of functional electrical stimulation (FES) is presented. In particular, electromyography (EMG)-initiated electrical muscle stimulation--but not electrical muscle stimulation alone--improves the motor function of the hemiparetic arm and hand. Triggered electrical stimulation is reported to be more effective than untriggered electrical stimulation in facilitating upper extremity motor recovery following stroke. Power-assisted FES induces greater muscle contraction by electrical stimulation in proportion to the voluntary integrated EMG signal picked up, which is regulated by a closed-loop control system. Power-assisted FES and motor point block for antagonist muscles have been applied with good results as a new hybrid FES therapy in an outpatient rehabilitation clinic for patients with stroke. Furthermore, a daily home program therapy with power-assisted FES using new equipment has been able to effectively improve wrist and finger extension and shoulder flexion. Proprioceptive sensory feedback might play an important role in power-assisted FES therapy. Although many physiotherapeutic modalities have been established, conclusive proof of their benefit and physiological models of their effects on neuronal structures and processes are still missing. A multichannel near-infrared spectroscopy study to noninvasively and dynamically measure hemoglobin levels in the brain during functional activity has shown that cerebral blood flow in the sensory-motor cortex on the injured side is higher during a power-assisted FES session than during simple active movement or simple electrical stimulation. Nevertheless, evidence-based strategies for motor rehabilitation are more easily available, particularly for patients with hemiparesis.     

Motor learning after stroke: Is skill acquisition a prerequisite for contralesional neuroplastic change?

Limited data directly characterize the dynamic evolution of brain activity associated with motor learning after stroke. The current study considered whether sequence-specific motor skill learning or increasing non-specific use of the hemiparetic upper extremity drive functional reorganization of the contralesional motor cortex after stroke. Eighteen individuals with chronic middle cerebral artery stroke practiced one of two novel motor tasks; a retention test occurred on a separate fifth day. Using the hemiparetic arm, participants performed a serial targeting task during two functional MRI scans (day one and retention). Participants were randomized into either a task-specific group, who completed three additional sessions of serial targeting practice, or a general arm use group, who underwent three training sessions of increased but non-task specific use of the hemiparetic arm. Both groups performed a repeated sequence of responses that may be learned, and random sequences of movement, which cannot be learned. Change in reaction and movement time for the repeated sequence indexed motor learning; shifts in the laterality index (LI) within primary motor cortex (M1) for repeated and random sequences illustrated training effects on brain activity. Task-specific practice of the repeated sequence facilitated motor learning and shifted the LI for M1 as shown by a reduced volume of contralesional cortical activity. Random sequence performance did not stimulate motor learning or alter the LI within the task-specific training group. Further, between-group comparisons showed that increasing general arm use did not induce motor learning or alter brain activity for either random or repeated sequences. Motor skill learning of a repeated sequence altered cortical activation by inducing a more normal, contralateral pattern of brain activation. Our data suggest that task-specific motor learning may be an important stimulant for neuroplastic change and can remediate maladaptive patterns of brain activity after stroke.     

fMRI reliability in subjects with stroke

Functional MRI (fMRI) has become one of the most commonly used neuroimaging tools to assess the cortical effects associated with rehabilitation, learning, or disease recovery in subjects with stroke. Despite this, there has been no systematic study of the reliability of the fMR signal in this population. The purpose of this study was to examine the within- and between-session reliability of fMRI in cortical and cerebellar structures in subjects with stroke during a complex, continuous visual motor task performed with the less affected hand. Nine subjects with stroke underwent four testing trials during two sessions separated by three weeks. Subjects performed a drawing task using an MRI compatible joystick while in the MRI. Methods of analysis evaluated included: percent signal intensity change, active voxel count and a voxel by voxel stat value analysis within and between testing sessions. Reliability was determined with Interclass correlation coefficients (ICC) in the following regions of interest: primary motor (M1), primary sensory (S1), premotor cortex (PMC), medial cerebellum (MCB), and lateral cerebellum (LCB). Results indicate that intensity change has superior reliability to the other methods of analysis (Average ICC across brain regions and trials: intensity change: 0.73, voxel count: 0.58, voxel by voxel: 0.67) and that generally with any analysis method, within-session reliability was higher than between-session, as indicated by higher ICC values across brain regions. Overall, when comparing between-session results, moderate to good reliability was obtained with intensity change (ICC: M1: 0.52, S1: 0.80, SMA: 0.78, PMC: 0.94, MCB: 0.86, and LCB: 0.59). These results show good reliability in subjects with stroke when performing a continuous motor task. These findings give confidence for interpreting fMRI test/retest research in subjects with stroke.     

Increased cognitive load during simple and complex motor tasks in acute stage after stroke.

The aim of this study was to assess the activation of primary motor cortex, prefrontal cortex and parietal cortex during simple and complex motor tasks performed with the hemiparetic and non-hemiparetic hand. METHODS: Seven patients after stroke in the left brain hemisphere were included in the study. Functional magnetic resonance imaging (fMRI) was performed in the first and third week, and in three patients also three months after the stroke. RESULTS: Performance of both the simple and the complex tasks with the hemiparetic or non-hemiparetic hand resulted in activations of the motor cortex, prefrontal cortex and parietal cortex in majority of the consecutive fMRI sessions. Three months after the stroke fMRI data revealed reduced activation of primary motor cortex and parietal cortex in the contralesional hemisphere during the performance of the simple task by the hemiparetic hand. During the complex task, the reduction of activation was less prominent. CONCLUSIONS: Results of the present study suggest that in mildly impaired stroke patients a bilateral activation of prefrontal and parietal cortex may participate in the recovery process from stroke. The potential for measurement of cortical rehabilitation is discussed.     

Motor hand recovery after stroke. Prognostic yield of early transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) was performed in 20 patients within the first days after stroke. Motor evoked potentials (MEPs) were bilaterally recorded over thenar eminence muscles, and central motor conduction time (CMCT), amplitude of the MEPs (A%M) and threshold intensity compared between both sides. Six months later the patients were reexamined. Within the first days after stroke the obtention of MEPs at rest or during voluntary muscle activation have a favorable prognostic value. All patients with early response by TMS reached a good motor function in the following months. The follow-up showed that the electrophysiological improvement was closely related to clinical recovery of the hand function. However, even in cases with a good recovery, the CMCT and, mainly, the A%M, may be significantly different related to those in normal hand. TMS may be an early and valuable prognostic indicator of hand function recovery after stroke, and their prognostic yield is higher than clinical evaluation and CT study. TMS is a quantifiable method of motor disability and may have practical application in the management and rehabilitation therapy in stroke patients.     

缺血性卒中患者脑运动区域协调性功能影像学研究

目的　评估缺血性脑卒中患者颅脑神经解剖学与脑区功能学的关联性,进一步挖掘缺血性卒中发生的神经机制。 方法　采集15例健康对照组和19例亚急性缺血性脑卒中上肢偏瘫患者,利用计算神经影像学计算个性化颅脑内部半球功能连接指标,采集治疗前后临床康复评分作统计相关分析。 结果　（1）与对照组相比,卒中患者大脑半球功能连接显著降低,差异有统计学意义(T=-10.077, P<0.001);（2）病灶异常集中于补充运动区（P=0.02）和中央前回(P=0.03),差异有统计学意义;（3）药物治疗前后患者组中央前回中的功能连接值与康复评分量表呈正相关,差异有统计学意义（r=0.29,P=0.03）。 结论　皮质下缺血性脑卒中患者大脑运动区域的半球间功能连接减少,可作为临床诊断和康复评估提供新的途径。     

Use of a Novel Robotic Interface to Study Finger Motor Control

Stroke is the leading cause of permanent adult disability in the U.S., frequently resulting in chronic motor impairments. Rehabilitation of the upper limb, particularly the hand, is especially important as arm and hand deficits post-stroke limit the performance of activities of daily living and, subsequently, functional independence. Hand rehabilitation is challenging due to the complexity of motor control of the hand. New instrumentation is needed to facilitate examination of the hand. Thus, a novel actuated exoskeleton for the index finger, the FingerBot, was developed to permit the study of finger kinetics and kinematics under a variety of conditions. Two such novel environments, one applying a spring-like extension torque proportional to angular displacement at each finger joint and another applying a constant extension torque at each joint, were compared in 10 stroke survivors with the FingerBot. Subjects attempted to reach targets located throughout the finger workspace. The constant extension torque assistance resulted in a greater workspace area (p < 0.02) and a larger active range of motion for the metacarpophalangeal joint (p < 0.01) than the spring-like assistance. Additionally, accuracy in terms of reaching the target was greater with the constant extension assistance as compared to no assistance. The FingerBot can be a valuable tool in assessing various hand rehabilitation paradigms following stroke.     

MRI & MRS assessment of the role of the tumour microenvironment in response to therapy

MRI and MRS techniques are being applied to the characterisation of various aspects of the tumour microenvironment and to the assessment of tumour response to therapy. For example, kinetic parameters describing tumour blood vessel flow and permeability can be derived from dynamic contrast-enhanced MRI data and have been correlated with a positive tumour response to antivascular therapies. The ongoing development and validation of noninvasive, high-resolution anatomical/molecular MR techniques will equip us with the means to detect specific tumour biomarkers early on, and then to monitor the efficacy of cancer treatments efficiently and reliably, all within a clinically relevant time frame. Reliable tumour microenvironment imaging biomarkers will provide obvious advantages by enabling tumour-specific treatment tailoring and potentially improving patient outcome. However, for routine clinical application across many disease types, such imaging biomarkers must be quantitative, robust, reproducible, sufficiently sensitive and cost-effective. These characteristics are all difficult to achieve in practice, but image biomarker development and validation have been greatly facilitated by an increasing number of pertinent preclinical in vivo cancer models. Emphasis must now be placed on discovering whether the preclinical results translate into an improvement in patient care and, therefore, overall survival.     

MRI of stroke using hyperpolarized 129Xe

Because there is no background signal from xenon in biological tissue, and because inhaled xenon is delivered to the brain by blood flow, we would expect a perfusion deficit, such as is seen in stroke, to reduce the xenon concentration in the region of the deficit. Thermal polarization yields negligible xenon signal relative to hyperpolarized xenon; therefore, hyperpolarized xenon can be used as a tracer of cerebral blood flow. Using a rat permanent right middle cerebral artery occlusion model, we demonstrated that hyperpolarized ¹²⁹Xe MRI is able to detect, in vivo, the hypoperfused area of focal cerebral ischemia, that is the ischemic core area of stroke. To the best of our knowledge, this is the first time that hyperpolarized ¹²⁹Xe MRI has been used to explore normal and abnormal cerebral perfusion. Our study shows a novel application of hyperpolarized ¹²⁹Xe MRI for imaging stroke, and further demonstrates its capacity to serve as a complementary tool to proton MRI for the study of the pathophysiology during brain hypoperfusion. Copyright © 2010 John Wiley & Sons, Ltd.     

Exoskeleton robots for upper-limb rehabilitation: state of the art and future prospects

Current health services are struggling to provide optimal rehabilitation therapy to victims of stroke. This has motivated researchers to explore the use of robotic devices to provide rehabilitation therapy for strokepatients. This paper reviews the recent progress of upper limb exoskeleton robots for rehabilitation treatment of patients with neuromuscular disorders. Firstly, a brief introduction to rehabilitation robots will be given along with examples of existing commercial devices. The advancements in upper limb exoskeleton technology and the fundamental challenges in developing these devices are described. Potential areas for future research are discussed.     

Cortical excitability changes following grasping exercise augmented with electrical stimulation

Rehabilitation with augmented electrical stimulation can enhance functional recovery after stroke, and cortical plasticity may play a role in this process. The purpose of this study was to compare the effects of three training paradigms on cortical excitability in healthy subjects. Cortical excitability was evaluated by analysing the input–output relationship between transcranial magnetic stimulation intensity and motor evoked potentials (MEPs) from the flexor muscles of the fingers. The study was performed with 25 healthy volunteers who underwent 20-min simulated therapy sessions of: (1) functional electrical stimulation (FES) of the finger flexors and extensors, (2) voluntary movement (VOL) with sensory stimulation, and (3) therapeutic FES (TFES) where the electrical stimulation augmented voluntary activation. TFES training produced a significant increase in MEP magnitude throughout the stimulation range, suggesting an increase in cortical excitability. In contrast, neither the FES nor voluntary movement alone had such an effect. These results suggest that the combination of voluntary effort and FES has greater potential to induce plasticity in the motor cortex and that TFES might be a more effective approach in rehabilitation after stroke than FES or repetitive voluntary training alone.