Cortical inhibition and habituation to evoked potentials: relevance for pathophysiology of migraine

Dysfunction of neuronal cortical excitability has been supposed to play an important role in etiopathogenesis of migraine. Neurophysiological techniques like evoked potentials (EP) and in the last years non-invasive brain stimulation techniques like transcranial magnetic stimulation (TMS) and transcranial direct current stimulation gave important contribution to understanding of such issue highlighting possible mechanisms of cortical dysfunctions in migraine. EP studies showed impaired habituation to repeated sensorial stimulation and this abnormality was confirmed across all sensorial modalities, making defective habituation a neurophysiological hallmark of the disease. TMS was employed to test more directly cortical excitability in visual cortex and then also in motor cortex. Contradictory results have been reported pointing towards hyperexcitability or on the contrary to reduced preactivation of sensory cortex in migraine. Other experimental evidence speaks in favour of impairment of inhibitory circuits and analogies have been proposed between migraine and conditions of sensory deafferentation in which down-regulation of GABA circuits is considered the more relevant pathophysiological mechanism. Whatever the mechanism involved, it has been found that repeated sessions of high-frequency rTMS trains that have been shown to up-regulate inhibitory circuits could persistently normalize habituation in migraine. This could give interesting insight into pathophysiology establishing a link between cortical inhibition and habituation and opening also new treatment strategies in migraine.     

Noninvasive Brain Stimulation Improves Hemispatial Neglect After Stroke: A Systematic Review and Meta-Analysis

Objective

To evaluate the effectiveness of noninvasive brain stimulation (NIBS)—repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS)—on hemispatial neglect and performance in activities of daily living (ADL) after stroke.

Non-invasive brain stimulation for the lower limb after stroke: what do we know so far and what should we be doing next?

Background: Non-invasive brain stimulation (NIBS) is promising as an adjuvant to rehabilitation of motor function after stroke. Despite numerous studies and reviews for the upper limb, NIBS targeting the lower limb and gait recovery after stroke is a newly emerging field of research. Purpose: To summarize findings from studies using NIBS to target the lower limb in stroke survivors. Methods: This narrative review describes studies of repetitive transcranial magnetic stimulation, paired associative stimulation and transcranial direct current stimulation with survivors of stroke. Results: NIBS appears capable of inducing changes in cortical excitability and lower limb function, but stimulation parameters and study designs vary considerably making it difficult to determine effectiveness. Conclusions: Future research should systematically assess differences in response with different stimulation parameters, test measures for determining who would be most likely to benefit and assess effectiveness with large samples before NIBS can be considered for use in clinical practice.

• Implications for Rehabilitation

• Stroke is a leading cause of disability, often resulting in dependency in activities of daily living and reduced quality of life.

• Non-invasive brain stimulation has received considerable interest as a potential adjuvant to rehabilitation after stroke and this review summarizes studies targeting the lower limb and gait recovery.

• Non-invasive brain stimulation can be used to modulate excitability of lower limb muscle representations and can lead to improvements in motor performance in stroke survivors.

• Non-invasive brain stimulation for gait recovery needs further investigation before translation to clinical practice is possible.

     

Comparison of Neuroplastic Responses to Cathodal Transcranial Direct Current Stimulation and Continuous Theta Burst Stimulation in Subacute Stroke

Objective

To investigate the effects of cathodal transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) on neural network connectivity and motor recovery in individuals with subacute stroke.

Noninvasive Brain Stimulation for Rehabilitation of Pediatric Motor Disorders Following Brain Injury: Systematic Review of Randomized Controlled Trials

ObjectiveTo assess the evidence of the effectiveness of noninvasive brain stimulation (NIBS) for rehabilitation of pediatric motor disorders after brain injury.Data SourcesOvid, Cochrane, Science Direct, Web of Science, EBSCOhost, PubMed, and Google Scholar databases were searched up to August 2017 by 2 independent reviewers.Study SelectionRandomized controlled trials (RCTs) published in English were included if they met the following criteria. Population: Pediatric patients with motor disorders following brain injury. Intervention: NIBS, including transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS). Outcomes: Measures related to motor disorders (upper limb functional abilities, gait, balance, and spasticity). Fourteen RCTs were included (10 studies used tDCS, while 4 studies used rTMS).Data ExtractionPredefined data were tabulated by 1 reviewer and verified by another reviewer. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale; also levels of evidence adapted from Sackett were used.Data SynthesisA grouped meta-analysis was performed on balance, gait parameters, and upper limb function. Data were pooled using a random-effects model to assess the immediate effect and 1-month follow-up of NIBS. According to the PEDro scale, 3 studies were excellent, 8 studies were good, and 3 studies were fair. The level of evidence of all of the included studies was 1b, except for 3 studies with grade 2a. There were significant improvements in all upper limb functions (standardized mean differences [SMDs] ranging from 0.94 to 1.83 [P values=.0001]), balance (SMDs ranging between -0.48 to 0.83 [P values<.05]) and some gait variables.ConclusionPediatric patients with brain injury can be safely stimulated by NIBS, and there is evidence for the efficacy of rTMS in improving upper limb function, and tDCS in improving balance and majority of gait variables with persisted effects for 1 month. The efficacy of spasticity is uncertain.     

Acute effects of bi-hemispheric transcranial direct current stimulation on the neuromuscular function of patients with chronic stroke: A randomized controlled study

BackgroundMuscle weakness in patients with chronic stroke is due to neuromuscular disorders such as muscle atrophy, loss of voluntary activation or weak muscle contractile properties which are majored by the imbalance of interhemispheric inhibition following stroke. In patients with chronic stroke, unilateral transcranial direct current stimulation improved the maximal isometric strength of paretic knee extensors, but bilateral transcranial direct current stimulation failed to improve concentric strength. This study aimed to assess if a bilateral current stimulation improves isometric maximal strength, voluntary activation and contractile properties of knee extensors in patients with chronic stroke.MethodsThirteen patients with chronic stroke and eight young healthy individuals participated in this randomized, simple-blinded, crossover study that included two experimental sessions: one with sham bilateral transcranial direct current stimulation and another with effective bilateral transcranial direct current stimulation (20 min, 2 mA). In the stroke patients, the anode was placed over the primary motor cortex of the affected hemisphere and the cathode over the contralateral primary motor cortex. In healthy participants, the brain side targeted by the anode and the cathode was randomly assigned. In each session, participants performed three assessments of strength, voluntary activation and contractile properties: before, during and after effective/sham bilateral transcranial direct current stimulation.FindingsBilateral transcranial direct current stimulation had no effect on any neuromuscular assessments in both groups (All P values > 0.05, partial eta-squares varied from 0.02 to 0.06).InterpretationA single session of bilateral transcranial direct current stimulation did not compensate muscular weakness of knee extensors in patients with chronic stroke.     

硬膜外植入式皮质刺激脑卒中患者提高神经网络功能

背景：硬膜外植入式皮质刺激兼顾了经颅磁刺激、经颅直流电刺激、硬膜下皮质刺激和深部脑刺激的优点,可显著改善脑卒中后的肢体运动与语言功能。 目的：综述近年来有关硬膜外植入式皮质刺激在脑卒中康复中的研究及其临床应用。 方法：由第一作者应用计算机检索1995年1月至2014年4月PubMed数据库及中国期刊全文数据库文献,检索关键词为“cortical stimulation,extradural motor cortex stimulation,extradural cortical implants,extraduralcorticalstimulation,stroke,rehabilitation;皮质刺激,硬膜外电刺激,硬膜外皮质植入,硬膜外皮质刺激,脑卒中,康复”。纳入有关硬膜外植入式皮质刺激在脑卒中后运动与言语障碍中应用的文章。结果与结论：硬膜外皮质刺激是植入式皮质刺激,其优势是侵入性小、高度精确性和经硬膜与大脑密切接触,对缺乏有效治疗的脑卒中慢性期运动和语言障碍患者来说,这有可能是一种新的治疗方法。硬膜外皮质刺激通过促进神经可塑性、促进病灶周围结构与功能改变、提高神经网络功能、促进大脑半球间功能平衡及增加感觉输入来改善脑卒中后的肢体运动功能与语言功能。     

Cerebellar stimulation and gait recovery北大核心CSCD

BACKGROUND AND OBJECTIVE After a stroke,the contralesional cerebellum is implicated in functional reorganization of the motor network.In animal models,stitnulation of the cerebellar-cortical networks has been found to improve recovery.This study assessed the effect of cerebellar intermittent Omega-burst stimulation(CRB-iTBS),a variation of repetitive transcranial magnetic stimulation(rTMS),on gait recovery after a stroke.     

康复治疗对脑卒中后脑网络运动功能重塑的磁共振研究进展

随着脑卒中后运动功能障碍研究的不断深入,功能磁共振成像(fMRI)受到广泛关注.脑卒中后皮质下病灶影响附近或远端相关脑区,导致运动功能障碍.镜像神经元疗法、重复性经颅磁、经颅电刺激可通过无创方式激活大脑皮质相关区域,恢复大脑半球之间的平衡,对全脑网络环路有调节作用,但经颅电刺激缺乏A级证据.针灸虽能广泛调节全脑功能网络...     

Virtual Reality and Noninvasive Brain Stimulation in Stroke: How Effective Is Their Combination for Upper Limb Motor Improvement?—A Meta-Analysis

Background

Efforts to augment post-stroke upper limb (UL) motor improvement include the use of newer interventions such as noninvasive brain stimulation (NIBS) and task practice in virtual reality environments (VEs). Despite increasing interest in using a combination of these 2 interventions, the effectiveness of this combination to enhance UL motor improvement outcomes has not been examined.

Using non-invasive brain stimulation to augment motor training-induced plasticity

Therapies for motor recovery after stroke or traumatic brain injury are still not satisfactory. To date the best approach seems to be the intensive physical therapy. However the results are limited and functional gains are often minimal. The goal of motor training is to minimize functional disability and optimize functional motor recovery. This is thought to be achieved by modulation of plastic changes in the brain. Therefore, adjunct interventions that can augment the response of the motor system to the behavioural training might be useful to enhance the therapy-induced recovery in neurological populations. In this context, noninvasive brain stimulation appears to be an interesting option as an add-on intervention to standard physical therapies. Two non-invasive methods of inducing electrical currents into the brain have proved to be promising for inducing long-lasting plastic changes in motor systems: transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). These techniques represent powerful methods for priming cortical excitability for a subsequent motor task, demand, or stimulation. Thus, their mutual use can optimize the plastic changes induced by motor practice, leading to more remarkable and outlasting clinical gains in rehabilitation. In this review we discuss how these techniques can enhance the effects of a behavioural intervention and the clinical evidence to date.     

Hand function improvement with low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere in a severe case of stroke

Previous research has shown that low-frequency rTMS of the unaffected hemisphere can improve motor function in acute and chronic stroke patients. However, these studies only investigated patients with mild or moderate motor deficits. We report a case of a stroke patient with a severe motor impairment who underwent sham and active repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere and had significantly improved motor function after active, but not after sham, stimulation of the unaffected primary motor cortex. In an additional session of active rTMS, this patient maintained and further enhanced the initial motor improvement. This case report shows that inhibitory rTMS of the unaffected hemisphere can also be beneficial for stroke patients with severe motor deficits and suggests that this approach of noninvasive brain stimulation should be further investigated in this population of patients.     

Motor and parietal cortex stimulation for phantom limb pain and sensations

Limb amputation may lead to chronic painful sensations referred to the absent limb, ie phantom limb pain (PLP), which is likely subtended by maladaptive plasticity. The present study investigated whether transcranial direct current stimulation (tDCS), a noninvasive technique of brain stimulation that can modulate neuroplasticity, can reduce PLP. In 2 double-blind, sham-controlled experiments in subjects with unilateral lower or upper limb amputation, we measured the effects of a single session of tDCS (2 mA, 15 min) of the primary motor cortex (M1) and of the posterior parietal cortex (PPC) on PLP, stump pain, nonpainful phantom limb sensations and telescoping. Anodal tDCS of M1 induced a selective short-lasting decrease of PLP, whereas cathodal tDCS of PPC induced a selective short-lasting decrease of nonpainful phantom sensations; stump pain and telescoping were not affected by parietal or by motor tDCS. These findings demonstrate that painful and nonpainful phantom limb sensations are dissociable phenomena. PLP is associated primarily with cortical excitability shifts in the sensorimotor network; increasing excitability in this system by anodal tDCS has an antalgic effect on PLP. Conversely, nonpainful phantom sensations are associated to a hyperexcitation of PPC that can be normalized by cathodal tDCS. This evidence highlights the relationship between the level of excitability of different cortical areas, which underpins maladaptive plasticity following limb amputation and the phenomenology of phantom limb, and it opens up new opportunities for the use of tDCS in the treatment of PLP.     

Innovative technologies applied to sensorimotor rehabilitation after stroke

Innovative technologies for sensorimotor rehabilitation after stroke have dramatically increased these past 20 years. Based on a review of the literature on “Medline” and “Web of Science” between 1990 and 2013, we offer an overview of available tools and their current level of validation. Neuromuscular electric stimulation and/or functional electric stimulation are widely used and highly suspected of being effective in upper or lower limb stroke rehabilitation. Robotic rehabilitation has yielded various results in the literature. It seems to have some effect on functional capacities when used for the upper limb. Its effectiveness in gait training is more controversial. Virtual reality is widely used in the rehabilitation of cognitive and motor impairments, as well as posture, with admitted benefits. Non-invasive brain stimulation (rTMS and TDCS) are promising in this indication but clinical evidence of their effectiveness is still lacking. In the same manner, these past five years, neurofeedback techniques based on brain signal recordings have emerged with a special focus on their therapeutic relevance in rehabilitation. Technological devices applied to rehabilitation are revolutionizing our clinical practices. Most of them are based on advances in neurosciences allowing us to better understand the phenomenon of brain plasticity, which underlies the effectiveness of rehabilitation. The acceptation and “real use” of those devices is still an issue since most of them are not easily available in current practice.     

Neural correlates of age-related changes in cortical neurophysiology

Functional imaging studies of cortical motor systems in humans have demonstrated age-related reorganisation often attributed to anatomical and physiological changes. In this study we investigated whether aspects of brain activity during a motor task were influenced not only by age, but also by neurophysiological parameters of the motor cortex contralateral to the moving hand. Twenty seven right-handed volunteers underwent functional magnetic resonance imaging whilst performing repetitive isometric right hand grips in which the target force was parametrically varied between 15 and 55% of each subject's own maximum grip force. For each subject we characterised two orthogonal parameters, B(G) (average task-related activity for all hand grips) and B(F) (the degree to which task-related activity co-varied with peak grip force). We used transcranial magnetic stimulation (TMS) to assess task-related changes in interhemispheric inhibition from left to right motor cortex (IHIc) and to perform measures relating to left motor cortex excitability during activation of the right hand. Firstly, we found that B(G) in right (ipsilateral) motor cortex was greater with increasing values of age(2) and IHIc. Secondly, B(F) in left ventral premotor cortex was greater in older subjects and in those in whom contralateral M1 was less responsive to TMS stimulation. In both cases, neurophysiological parameters accounted for variability in brain responses over and above that explained by ageing. These results indicate that neurophysiological markers may be better indicators of biological ageing than chronological age and point towards the mechanisms by which reconfiguration of distributed brain networks occurs in the face of degenerative changes.     

Effect of single-session dual-tDCS before physical therapy on lower-limb performance in sub-acute stroke patients: A randomized sham-controlled crossover study

Anodal stimulation increases cortical excitably, whereas cathodal stimulation decreases cortical excitability. Dual transcranial direct current stimulation (tDCS; anodal over the lesioned hemisphere, cathodal over the non-lesioned hemisphere) was found to enhance motor learning. The corresponding tDCS-induced changes were reported to reduce the inhibition exerted by the unaffected hemisphere on the affected hemisphere and restore the normal balance of the interhemispheric inhibition. Most studies were devoted to the possible modification of upper-limb motor function after tDCS; however, almost no study has demonstrated its effects on lower-limb function and gait, which are also commonly disordered in stroke patients with motor deficits. In this randomized sham-controlled crossover study, we included 19 patients with sub-acute stroke. Participants were randomly allocated to receive real or sham dual-tDCS followed by conventional physical therapy with an intervention interval of at least 1 week. Dual-tDCS was applied over the lower-limb M1 at 2-mA intensity for 20 min. Lower-limb performance was assessed by the Timed Up and Go (TUG) and Five-Times-Sit-To-Stand (FTSTS) tests and muscle strength was assessed by peak knee torque of extension. We found a significant increase in time to perform the FTSST for the real group, with improvements significantly greater than for the sham group; the TUG score was significantly increased but not higher than for the sham group. An after-effect on FTSTS was found at approximately 1 week after the real intervention. Muscle strength was unchanged in both limbs for both real and sham groups. Our results suggest that a single session of dual-tDCS before conventional physical therapy could improve sit-to-stand performance, which appeared to be improved over conventional physical therapy alone. However, strength performance was not increased after the combination treatment.     

The potential for non-invasive brain stimulation to improve function after amputation

Purpose: Lower limb amputee rehabilitation has traditionally focussed on restoration of gait and balance through use of prosthetic limbs and mobility aids. Despite these efforts, some amputees continue to experience difficulties with mastering prosthetic mobility. Emerging techniques in rehabilitation, such as non-invasive brain stimulation (NIBS), may be an appropriate tool to enhance prosthetic rehabilitation outcomes by promoting “normal” brain reorganisation and function. The purpose of this review is to highlight the potential of NIBS to improve functional outcomes for lower limb amputees. Methods: To demonstrate the rationale for applying NIBS to amputees, this study will first review literature regarding human motor control of gait, followed by neurophysiological reorganisation of the motor system after amputation and the relationship between brain reorganisation and gait function. We will conclude by reviewing literature demonstrating application of NIBS to lower limb muscle representations and evidence supportive of subsequent functional improvements. Results: Imaging, brain stimulation and behavioural evidence indicate that the cortex contributes to locomotion in humans. Following amputation both hemispheres reorganise with evidence suggesting brain reorganisation is related to functional outcomes in amputees. Previous studies indicate that brain stimulation techniques can be used to selectively promote neuroplasticity of lower limb cortical representations with improvements in function.

Conclusions: We suggest NIBS has the potential to transform lower limb amputee rehabilitation and should be further investigated.

• Implications for Rehabilitation

• Despite extensive rehabilitation some amputees continue to experience difficulty with prosthetic mobility

• Brain reorganisation following amputation has been related to functional outcomes and may be an appropriate target for novel interventions

• Non-invasive brain stimulation is a promising tool which has potential to improve functional outcomes for lower limb amputees

     

Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: A review

Numerous studies have recently been published on improving upper-limb motor function after stroke. There has been a particular interest in brain stimulation techniques, which could promote brain plasticity. In this review, transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) are presented as techniques that could be relevant in Physical Medicine and Rehabilitation (PM&R) centers in the future. We are presenting a comprehensive literature review on the studies using tDCS or rTMS for upper-limb rehabilitation after a stroke. Both techniques have shown their ability to modify cortical excitability and to transitorily improve upper-limb function after one single stimulation session. The first placebo-controlled, blinded therapeutic trials, which included repeated daily sessions, seem quite promising, and deserve to be validated by further trials.     

Changes in transcranial magnetic stimulation outcome measures in response to upper-limb physical training in stroke: A systematic review of randomized controlled trials

Background

Physical training is known to be an effective intervention to improve sensorimotor impairments after stroke. However, the link between brain plastic changes, assessed by transcranial magnetic stimulation (TMS), and sensorimotor recovery in response to physical training is still misunderstood. We systematically reviewed reports of randomized controlled trials (RCTs) involving the use of TMS over the primary motor cortex (M1) to probe brain plasticity after upper-limb physical training interventions in people with stroke.

Integrated technology for evaluation of brain function and neural plasticity

The study of neural plasticity has expanded rapidly in the past decades and has shown the remarkable ability of the developing, adult, and aging brain to be shaped by environmental inputs in health and after a lesion. Robust experimental evidence supports the hypothesis that neuronal aggregates adjacent to a lesion in the sensorimotor brain areas can take over progressively the function previously played by the damaged neurons. It definitely is accepted that such a reorganization modifies sensibly the interhemispheric differences in somatotopic organization of the sensorimotor cortices. This reorganization largely subtends clinical recovery of motor performances and sensorimotor integration after a stroke. Brain functional imaging studies show that recovery from hemiplegic strokes is associated with a marked reorganization of the activation patterns of specific brain structures. To regain hand motor control, the recovery process tends over time to bring the bilateral motor network activation toward a more normal intensity/extent, while overrecruiting simultaneously new areas, perhaps to sustain this process. Considerable intersubject variability exists in activation/hyperactivation pattern changes over time. Some patients display late-appearing dorsolateral prefrontal cortex activation, suggesting the development of "executive" strategies to compensate for the lost function. The AH in stroke often undergoes a significant "remodeling" of sensory and motor hand somatotopy outside the "normal" areas, or enlargement of the hand representation. The UH also undergoes reorganization, although to a lesser degree. Although absolute values of the investigated parameters fluctuate across subjects, secondary to individual anatomic variability, variation is minimal with regards to interhemispheric differences, due to the fact that individual morphometric characters are mirrored in the two hemispheres. Excessive interhemispheric asymmetry of the sensorimotor hand areas seems to be the parameter with highest sensitivity in describing brain reorganization after a monohemispheric lesion, and mapping motor and somatosensory cortical areas through focal TMS, fMRI, PET, EEG, and MEG is useful in studying hand representation and interhemispheric asymmetries in normal and pathologic conditions. TMS and MEG allow the detection of sensorimotor areas reshaping, as a result of either neuronal reorganization or recovery of the previously damaged neural network. These techniques have the advantage of high temporal resolution but also have limitations. TMS provides only bidimensional scalp maps, whereas MEG, even if giving three-dimensional mapping of generator sources, does so by means of inverse procedures that rely on the choice of a mathematical model of the head and the sources. These techniques do not test movement execution and sensorimotor integration as used in everyday life. fMRI and PET may provide the ideal means to integrate the findings obtained with the other two techniques. This multitechnology combined approach is at present the best way to test the presence and amount of plasticity phenomena underlying partial or total recovery of several functions, sensorimotor above all. Dynamic patterns of recovery are emerging progressively from the relevant literature. Enhanced recruitment of the affected cortex, be it spared perilesional tissue, as in the case of cortical stroke, or intact but deafferented cortex, as in subcortical strokes, seems to be the rule, a mechanism especially important in early postinsult stages. The transfer over time of preferential activation toward contralesional cortices, as observed in some cases, seems, however, to reflect a less efficient type of plastic reorganization, with some aspects of maladaptive plasticity. Reinforcing the use of the affected side can cause activation to increase again in the affected side with a corresponding enhancement of clinical function. Activation of the UH MI may represent recruitment of direct (uncrossed) corticospinal tracts and relate more to mirror movements, but it more likely reflects activity redistribution within preexisting bilateral, large-scale motor networks. Finally, activation of areas not normally engaged in the dysfunctional tasks, such as the dorsolateral prefrontal cortex or the superior parietal cortex in motor paralysis, might reflect the implication of compensatory cognitive strategies. An integrated approach with technologies able to investigate functional brain imaging is of considerable value in providing information on the excitability, extension, localization, and functional hierarchy of cortical brain areas. Deepening knowledge of the mechanisms regulating the long-term recovery (even if partial), observed for most neurologic sequelae after neural damage, might prompt newer and more efficacious therapeutic and rehabilitative strategies for neurologic diseases.