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.     

Compensation aids skilled reaching in aging and in recovery from forelimb motor cortex stroke in the rat

Compensatory movements mediate success in skilled reaching for food after stroke to the forelimb region of motor cortex (MtCx) in the rat. The present study asks whether the neural plasticity that enables compensation after motor stroke is preserved in aging. In order to avoid potential confounding effects of age-related negative-learning, rats were trained in a single pellet reaching task during young-adulthood. Subgroups were retested before and after contralateral forelimb MtCx stroke via pial stripping given at 3, 18, or 23 months of age. Over a two-month post-stroke rehabilitation period, end point measures were made of learned nonuse, recovery, retention, and performance ratings were made of reaching movement elements. Prior to stroke, young and aged rats maintained equivalent end point performance but older rats displayed compensatory changes in limb use as measured with ratings of the elements of forelimb movement. Following stroke, the aged groups of rats were more impaired on end point, movement, and anatomical measures. Nevertheless, the aged rats displayed substantial recovery via the use of compensatory movements. Thus, this study demonstrates that the neural plasticity that mediates compensatory movements after stroke in young adults is preserved prior to and following stroke in aging.     

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.     

Neural plasticity and bilateral movements: A rehabilitation approach for chronic stroke

Stroke interferes with voluntary control of motor actions. Although spontaneous recovery of function can occur, restoration of normal motor function in the hemiplegic upper limb is noted in fewer than 15% of individuals. However, there is increasing evidence to suggest that in addition to injury-related reorganization, motor cortex functions can be altered by individual motor experiences. Such neural plasticity has major implications for the type of rehabilitative training administered post-stroke. This review proposes that noteworthy upper extremity gains toward motor recovery evolve from activity-dependent intervention based on theoretical motor control constructs and interlimb coordination principles. Founded on behavioral and neurophysiological mechanisms, bilateral movement training/practice has shown great promise in expediting progress toward chronic stroke recovery in the upper extremity. Planning and executing bilateral movements post-stroke may facilitate cortical neural plasticity by three mechanisms: (a) motor cortex disinhibition that allows increased use of the spared pathways of the damaged hemisphere, (b) increased recruitment of the ipsilateral pathways from the contralesional or contralateral hemisphere to supplement the damaged crossed corticospinal pathways, and (c) upregulation of descending premotorneuron commands onto propriospinal neurons.     

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.     

From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia

Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues.     

Functional MRI using robotic MRI compatible devices for monitoring rehabilitation from chronic stroke in the molecular medicine era (Review)

The number of individuals suffering from stroke is increasing daily, and its consequences are a major contributor to invalidity in today's society. Stroke rehabilitation is relatively new, having been hampered from the longstanding view that lost functions were not recoverable. Nowadays, robotic devices, which aid by stimulating brain plasticity, can assist in restoring movement compromised by stroke-induced pathological changes in the brain which can be monitored by MRI. Multiparametric magnetic resonance imaging (MRI) of stroke patients participating in a training program with a novel Magnetic Resonance Compatible Hand-Induced Robotic Device (MR_CHIROD) could yield a promising biomarker that, ultimately, will enhance our ability to advance hand motor recovery following chronic stroke. Using state-of-the art MRI in conjunction with MR_CHIROD-assisted therapy can provide novel biomarkers for stroke patient rehabilitation extracted by a meta-analysis of data. Successful completion of such studies may provide a ground breaking method for the future evaluation of stroke rehabilitation therapies. Their results will attest to the effectiveness of using MR-compatible hand devices with MRI to provide accurate monitoring during rehabilitative therapy. Furthermore, such results may identify biomarkers of brain plasticity that can be monitored during stroke patient rehabilitation. The potential benefit for chronic stroke patients is that rehabilitation may become possible for a longer period of time after stroke than previously thought, unveiling motor skill improvements possible even after six months due to retained brain plasticity.     

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.     

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。     

经颅电刺激在卒中后运动康复领域的研究进展

由脑卒中造成的神经性损伤是目前导致运动功能障碍的主要病因之一,为社会和患者家庭带来了巨大的精神和经济负担。结合经颅电刺激的运动康复疗法为改善患者运动功能障碍、提高生活质量提供一种重要的治疗方式。经颅电刺激是一种无痛、非侵入式脑刺激方法,能够调节神经元胞内钙离子浓度、增强突触可塑性、调制神经放电频率、改变皮层兴奋性,从而实现对大脑神经活动的调控。回顾经颅电刺激的神经机制,在科研临床应用中的参数设置,以及安全性等问题,总结其在运动功能康复方面的成果以及目前亟待解决的问题。     

Age, experience, injury, and the changing brain

The fundamental concept in the emerging field of rehabilitation and brain plasticity is that although there is much constancy in brain function and organization across our lifetime, there is remarkable variability as well. This variability reflects the brain's capacity to alter its structure and function in reaction to environmental diversity as well as to perturbations including injury throughout the lifespan. Although the term brain plasticity is now widely used, it is not easily defined and is used to refer to changes at many levels in the nervous system ranging from molecular events, such as changes in gene expression, to behavior (e.g., Shaw & McEachern (Eds.) [2001]. Toward a Theory of Neuroplasticity. Philadelphia, USA: Psychology Press). The focus of our work has been to correlate changes in behavior, neuronal morphology, and the organization of motor maps after cortical injury throughout the lifespan. In this article, we review evidence we have collected from a rat model of normal development and the effects of brain injury, and comment on the general principals that may apply to human stroke and amblyopia.     

Plasticity in Cortical Motor Upper-Limb Representation Following Stroke and Rehabilitation: Two Longitudinal Multi-Joint fMRI Case-Studies

Motor dysfunction and recovery following stroke and rehabilitation are associated with primary motor cortex plasticity. To better track these effects we studied two patients with sub-acute sub-cortical stroke causing hemiparesis, who underwent an effective behavioral treatment termed Constraint Induced Movement Therapy (CIMT). The therapy involves 2 weeks of intensive motor training of the hemiparetic limb coupled with immobilization of the unaffected limb. The study included a longitudinal series of clinical evaluations and fMRI scans, before and after the treatment. The fMRI task included wrist, elbow, or ankle movements. Activity in the M1 upper-limb region of control subjects was stable, strictly contralateral, and similar in amplitude for elbow and wrist movements. These findings reflect the well-known contralateral motor control and support the idea of overlapping representations of adjacent joints in M1. In both patients, pre-CIMT activation patterns in M1 were tested twice and did not change significantly, were contralateral, and included elbow-wrist differences. Following CIMT, the clinical condition of both patients improved and three fMRI-explored prototypes were found: First, cluster position remained constant; Second, ipsilateral activity appeared in the unaffected hemispheres during hemiparetic movements; Third, patient-specific elbow-wrist inter and intra hemispheric differences were modified. All effects were long-lasting. We suggest that overlapping representations of adjacent joints contributed to the cortical plasticity observed following CIMT. Our findings should be confirmed by studying larger groups of homogeneous patients. Nevertheless, this study introduces multi-joint imaging studies and shows that it is both possible and valuable to carry it out in stroke patients.     

F wave measurements detecting changes in motor neuron excitability after ischaemic stroke

OBJECTIVE: To study mechanisms that are involved in the hyperexcitability of spinal motor neurons in upper motor neuron lesion, by means of F-wave measurements. METHODS: F waves from 44 hospitalized stroke patients and 35 healthy controls were recorded from abductor pollicis brevis muscles in the course of two experiments: (1) single stimuli following high-intensity ipsilateral cutaneous conditioning were used to stimulate the median nerve; (2) paired stimuli were given to the median nerve at gradually increasing interstimulus intervals to assess recovery curves. Mean F-wave amplitudes elicited by the conditioning stimuli were compared with mean F-wave amplitudes elicited by the test stimuli on both the hemiparetic and the unaffected side. RESULTS: There was no reduction on the hemiparetic side of mean F-wave amplitudes elicited following high-intensity ipsilateral cutaneous stimulation. The recovery of mean F-wave amplitude was completed at longer interstimulus intervals on the hemiparetic side than on the unaffected side and in controls. A correlation was found between this delay of recovery and hemiparetic severity. CONCLUSIONS: The results of our study support the role of changes in lower motor neuron membrane excitability in the enhancement of F wave amplitudes after stroke.     

基于脑卒中后运动康复领域的运动想象的研究

脑卒中后造成的神经性损伤是目前导致患者运动功能性障碍的主要原因之一,为社会和患者家庭造成巨大的精神和经济负担。运动想象易学习、成本低,是辅助脑卒中后患者康复的重要手段之一,对改善患者运动功能障碍、提高生活质量具有重要意义。本文主要总结运动想象对脑卒中后康复的积极作用,概述运动想象的生理表现和理论模式、运动想象能力的影响因素、运动想象能力的评分标准,并分析目前运动想象在辅助脑卒中后患者运动功能的康复治疗过程中存在的实验对象单一、评估方法主观化、实验设备分辨率低等缺陷,希望帮助脑卒中后患者更加科学、有效地使用运动想象疗法。     

Recovery of motor function after stroke

The human brain possesses a remarkable ability to adapt in response to changing anatomical (e.g., aging) or environmental modifications. This form of neuroplasticity is important at all stages of life but is critical in neurological disorders such as amblyopia and stroke. This review focuses upon our new understanding of possible mechanisms underlying functional deficits evidenced after adult-onset stroke. We review the functional interactions between different brain regions that may contribute to motor disability after stroke and, based on this information, possible interventional approaches to motor stroke disability. New information now points to the involvement of non-primary motor areas and their interaction with the primary motor cortex as areas of interest. The emergence of this new information is likely to impact new efforts to develop more effective neurorehabilitative interventions using transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) that may be relevant to other neurological disorders such as amblyopia.     

经颅磁刺激促进脑卒中功能恢复的作用机制

近年来国内脑卒中发病率逐年上升,经颅磁刺激以其无痛、无创的治疗优势应用于脑卒中患者的康复治疗中,但目前其促进脑卒中后运动功能恢复的作用机制尚不完全明确,本文从其调节刺激部位脑血流量、调节大脑皮层兴奋性、调节大脑半球双相平衡模型、诱导长时程效应、调节突触可塑性和促进轴突再生、调节神经递质和激活神经通路、改善神经元微环境和调节干细胞增殖分化的研究做一综述,以期为临床治疗提供参考。     

Hemiparetic stroke impairs anticipatory control of arm movement

Internal models are sensory motor mappings used by the nervous system to anticipate the force requirements of movement tasks. The ability to use internal models likely underlies the development of skillful control of the arm throughout life. It is currently unknown to what extent individuals with hemiparetic stroke can form and implement such internal models. To examine this issue, we measured whether such individuals could learn to anticipate forces applied to their arms by a lightweight robotic device as they practiced reaching to a target. Thirteen subjects with post-stroke hemiparesis were tested. Forces were applied to the arm, which curved the hand path in either the medial or lateral direction, as the subjects reached repeatedly towards a target located in front of them at their workspace boundary. The subjects exhibited a decreased ability to adapt to the perturbing forces with their hemiparetic arms. That is, they did not straighten their reaching path as well, compared to their ipsilesional arms, and they exhibited smaller aftereffects when the perturbing force was unexpectedly removed. The ability to adapt to the force improved significantly with decreasing impairment severity, as quantified using both clinical scales and quantitative strength measurements. Some subjects with strength reductions as severe as 60% were able to adapt to the fields, generating significant aftereffects. We conclude that hemiparetic stroke impairs the ability to implement internal models used for anticipatory control of arm movement, although even some severely weakened subjects retain at least a partial ability to form and use internal models. Finding ways to fully restore this adaptive ability, or to make use of what adaptive ability remains during rehabilitation, is an important goal for improving functional motor recovery. Electronic Publication     

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.     

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.     

Thinning,movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis

Plasticity of residual cortical tissue has been identified as an important mediator of functional post-stroke recovery. Many studies have been directed toward describing biochemical, electrophysiological, and cytoarchitectural changes in residual cortex and correlating them with functional changes. Additionally, after neonatal stroke the thickness of residual tissue can change, the tissue can move, and tissue can fill in the stroke core. The purpose of the present study was to systematically investigate and document possible gross morphological changes in peri-infarct tissue after forelimb motor cortex stroke in the adult rat. Rats received a unilateral forelimb motor cortex stroke of equivalent size by pial strip devascularization or photothrombotic occlusion and were then examined using histology or magnetic resonance imaging (MRI) at 1 h, 1, 3, 7, 14, or 31 days post-stroke. Middle cerebral artery occlusion was used as a control stroke procedure. Decreases in cortical thickness, volume, and neural density were found to extend far beyond the stroke infarct and included most of the sensorimotor regions of the stroke and intact hemispheres. Movement of residual tissue towards the infarct was observed and confirmed using anatomical markers placed in intact cortical tissue at the time of stroke induction. The results are discussed in relation to the idea that extensive time-dependent morphological changes that occur in residual tissue must be considered when evaluating plasticity-related cortical changes associated with post-stroke recovery of function.