Potential Of Noninvasive Brain Stimulation Research Articles

A Scoping Review on the Use of Non-Invasive Brain Stimulation Techniques for Persistent Post-Concussive Symptoms.

In the context of managing persistent post-concussive symptoms (PPCS), existing treatments like pharmacotherapy, cognitive behavioral therapy, and physical rehabilitation show only moderate effectiveness. The emergence of neuromodulation techniques in PPCS management has led to debates regarding optimal stimulation parameters and their overall efficacy. this scoping review involved a comprehensive search of PubMed and ScienceDirect databases, focusing on controlled studies examining the therapeutic potential of non-invasive brain stimulation (NIBS) techniques in adults with PPCS. Among the 940 abstracts screened, only five studies, encompassing 103 patients (12 to 29 per study), met the inclusion criteria. These studies assessed the efficacy of transcranial direct current stimulation (tDCS), or repetitive transcranial magnetic stimulation (rTMS), applied to specific brain regions (i.e., the left dorsolateral pre-frontal cortex (DLPFC) or left motor cortex (M1)) for addressing cognitive and psychological symptoms, headaches, and general PPCSs. The results indicated improvements in cognitive functions with tDCS. In contrast, reductions in headache intensity and depression scores were observed with rTMS, while no significant findings were noted for general symptoms with rTMS. although these pilot studies suggest promise for rTMS and tDCS in PPCS management, further research with larger-scale investigations and standardized protocols is imperative to enhance treatment outcomes for PPCS patients.

Brain stimulation for patients with multiple sclerosis: an umbrella review of therapeutic efficacy.

Multiple sclerosis patients often experience various symptoms that can greatly impact their quality of life. There are various brain stimulation techniques that have been evaluated for their ability to reduce the symptoms of multiple sclerosis. However, there is inconsistency in the specific stimulation methods used and the symptoms targeted in the existing research. This umbrella review conducted in order to evaluate the effectiveness of brain stimulation and identify limitations and gaps for further research. In this umbrella review, we conducted a searched on Web of Knowledge, PubMed, and Scopus database. We specifically looked for reviews, with or without meta-analyses, that have investigated the effects of brain stimulation methods on symptoms of multiple sclerosis. All articles were examined by AMSTAR 2 (A Measure Tool to Assess Systematic Review 2). We identified 155 articles, of which 14 were eligible for inclusion. Of those, five were qualitative studies and nine were meta-analyses. Among the included studies, four examined the use of deep brain stimulation, while ten investigated the therapeutic potential of noninvasive brain stimulation. Considering the heterogeneity of studies, the current evidence suggests that repetitive transcranial magnetic stimulation may be effective in treating pain and improving motor function, while transcranial direct current stimulation may be useful in alleviating fatigue and enhancing certain aspects of cognitive performance. Deep brain stimulation, on the other hand, appears to be effective in reducing tremors. However, further research is warranted to validate these findings and address the existing limitations in the field.

Modulation of Visually Induced Self-motion Illusions by α Transcranial Electric Stimulation over the Superior Parietal Cortex.

The growing popularity of virtual reality systems has led to a renewed interest in understanding the neurophysiological correlates of the illusion of self-motion (vection), a phenomenon that can be both intentionally induced or avoided in such systems, depending on the application. Recent research has highlighted the modulation of α power oscillations over the superior parietal cortex during vection, suggesting the occurrence of inhibitory mechanisms in the sensorimotor and vestibular functional networks to resolve the inherent visuo-vestibular conflict. The present study aims to further explore this relationship and investigate whether neuromodulating these waves could causally affect the quality of vection. In a crossover design, 22 healthy volunteers received high amplitude and focused α-tACS (transcranial alternating current stimulation) over the superior parietal cortex while experiencing visually induced vection triggered by optokinetic stimulation. The tACS was tuned to each participant's individual α peak frequency, with θ-tACS and sham stimulation serving as controls. Overall, participants experienced better quality vection during α-tACS compared with control θ-tACS and sham stimulations, as quantified by the intensity of vection. The observed neuromodulation supports a causal relationship between parietal α oscillations and visually induced self-motion illusions, with their entrainment triggering overinhibition of the conflict within the sensorimotor and vestibular functional networks. These results confirm the potential of noninvasive brain stimulation for modulating visuo-vestibular conflicts, which could help to enhance the sense of presence in virtual reality environments.

Anodal cerebellar t-DCS impacts skill learning and transfer on a robotic surgery training task

The cerebellum has demonstrated a critical role during adaptation in motor learning. However, the extent to which it can contribute to the skill acquisition of complex real-world tasks remains unclear. One particularly challenging application in terms of motor activities is robotic surgery, which requires surgeons to complete complex multidimensional visuomotor tasks through a remotely operated robot. Given the need for high skill proficiency and the lack of haptic feedback, there is a pressing need for understanding and improving skill development. We investigated the effect of cerebellar transcranial direct current stimulation applied during the execution of a robotic surgery training task. Study participants received either real or sham stimulation while performing a needle driving task in a virtual (simulated) and a real-world (actual surgical robot) setting. We found that cerebellar stimulation significantly improved performance compared to sham stimulation at fast (more demanding) execution speeds in both virtual and real-world training settings. Furthermore, participants that received cerebellar stimulation more effectively transferred the skills they acquired during virtual training to the real world. Our findings underline the potential of non-invasive brain stimulation to enhance skill learning and transfer in real-world relevant tasks and, more broadly, its potential for improving complex motor learning.

Effects of Non-invasive Brain Stimulation on Hereditary Ataxia: a Systematic Review and Meta-analysis.

Numerous studies have demonstrated the potential of non-invasive brain stimulation (NIBS) techniques as a viable treatment option for cerebellar ataxia. However, there is a notable dearth of research investigating the efficacy of NIBS specifically for hereditary ataxia (HA), a distinct subgroup within the broader category of cerebellar ataxia. This study aims to conduct a comprehensive systematic review and meta-analysis in order to assess the efficacy of various NIBS methods for the treatment of HA. A thorough review of the literature was conducted, encompassing both English and Chinese articles, across eight electrical databases. The focus was on original articles investigating the therapeutic effectiveness of non-invasive brain stimulation for hereditary ataxia, with a publication date prior to March 2023. Subsequently, a meta-analysis was performed specifically on randomized controlled trials (RCTs) that fulfilled the eligibility criteria, taking into account the various modalities of non-invasive brain stimulation. A meta-analysis was conducted, comprising five RCTs, which utilized the Scale for the Assessment and Rating of Ataxia (SARA) as the outcome measure to evaluate the effects of transcranial magnetic stimulation (TMS). The findings revealed a statistically significant mean decrease of 1.77 in the total SARA score following repetitive TMS (rTMS) (p=0.006). Subgroup analysis based on frequency demonstrated a mean decrease of 1.61 in the total SARA score after high-frequency rTMS (p=0.05), while no improvement effects were observed after low-frequency rTMS (p=0.48). Another meta-analysis was performed on three studies, utilizing ICARS scores, to assess the impact of rTMS. The results indicated that there were no statistically significant differences in pooled ICARS scores between the rTMS group and the sham group (MD=0.51, 95%CI: -5.38 to 6.39; p=0.87). These findings align with the pooled results of two studies that evaluated alterations in post-intervention BBS scores (MD=0.74, 95%CI: -5.48 to 6.95; p=0.82). Despite the limited number of studies available, this systematic review and meta-analysis have revealed promising potential benefits of rTMS for hereditary ataxia. However, it is strongly recommended that further high-quality investigations be conducted in this area. Furthermore, the significance of standardized protocols for NIBS in future studies was also emphasized.

The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue.

Following an acute COVID-19 infection, a large number of patients experience persisting symptoms for more than four weeks, a condition now classified as Long-COVID syndrome. Interestingly, the likelihood and severity of Long-COVID symptoms do not appear to be related to the severity of the acute COVID-19 infection. Fatigue is amongst the most common and debilitating symptoms of Long-COVID. Other symptomes include dyspnoea, chest pain, olfactory disturbances, and brain fog. Fatigue is also frequently reported in many other neurological diseases, affecting a broad range of everyday activities. However, despite its clinical significance, limited progress has been made in understanding its causes and developing effective treatment options. Non-invasive brain stimulation (NIBS) methods offer the unique opportunity to modulate fatigue-related maladaptive neuronal activity. Recent data show promising results of NIBS applications over frontoparietal regions to reduce fatigue symptoms. In this current paper, we review recent data on Long-COVID and Long-COVID-related fatigue (LCOF), with a special focus on cognitive fatigue. We further present widely used NIBS methods, such as transcranial direct current stimulation, transcranial alternating current stimulation, and transcutaneous vagus nerve stimulation and propose their use as possible therapeutic strategies to alleviate individual pathomechanisms of LCOF. Since NIBS methods are safe and well-tolerated, they have the potential to enhance the quality of life in a broad group of patients.

Effects of Non-Invasive Brain Stimulation on Post-Stroke Spasticity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

In recent years, the potential of non-invasive brain stimulation (NIBS) for the therapeutic effect of post-stroke spasticity has been explored. There are various NIBS methods depending on the stimulation modality, site and parameters. The purpose of this study is to evaluate the efficacy of NIBS on spasticity in patients after stroke. This systematic review and meta-analysis was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. PUBMED (MEDLINE), Web of Science, Cochrane Library and Excerpta Medica Database (EMBASE) were searched for all randomized controlled trials (RCTs) published before December 2021. Two independent researchers screened relevant articles and extracted data. This meta-analysis included 14 articles, and all included articles included 18 RCT datasets. The results showed that repetitive transcranial magnetic stimulation (rTMS) (MD = −0.40, [95% CI]: −0.56 to −0.25, p < 0.01) had a significant effect on improving spasticity, in which low-frequency rTMS (LF-rTMS) (MD = −0.51, [95% CI]: −0.78 to −0.24, p < 0.01) and stimulation of the unaffected hemisphere (MD = −0.58, [95% CI]: −0.80 to −0.36, p < 0.01) were beneficial on Modified Ashworth Scale (MAS) in patients with post-stroke spasticity. Transcranial direct current stimulation (tDCS) (MD = −0.65, [95% CI]: −1.07 to −0.22, p < 0.01) also had a significant impact on post-stroke rehabilitation, with anodal stimulation (MD = −0.74, [95% CI]: −1.35 to −0.13, p < 0.05) being more effective in improving spasticity in patients. This meta-analysis revealed moderate evidence that NIBS reduces spasticity after stroke and may promote recovery in stroke survivors. Future studies investigating the mechanisms of NIBS in addressing spasticity are warranted to further support the clinical application of NIBS in post-stroke spasticity.

Fatigue in Multiple Sclerosis: A Review of the Exploratory and Therapeutic Potential of Non-Invasive Brain Stimulation.

Fatigue is the most commonly reported symptom in patients with multiple sclerosis (MS). It is a worrisome, frequent, and debilitating manifestation that could occur at any time during the course of MS and in all its subtypes. It could engender professional, familial, and socioeconomic consequences and could severely compromise the patients' quality of life. Clinically, the symptom exhibits motor, cognitive, and psychosocial facets. It is also important to differentiate between perceived or subjective self-reported fatigue and fatigability which is an objective measure of decrement in the performance of cognitive or motor tasks. The pathophysiology of MS fatigue is complex, and its management remains a challenge, despite the existing body of literature on this matter. Hence, unraveling its neural mechanisms and developing treatment options that target the latter might constitute a promising field to explore. A PubMed/Medline/Scopus search was conducted to perform this review which aims (a) to reappraise the available electrophysiological studies that explored fatigue in patients with MS with a particular focus on corticospinal excitability measures obtained using transcranial magnetic stimulation and (b) to assess the potential utility of employing neuromodulation (i.e., non-invasive brain stimulation techniques) in this context. A special focus will be put on the role of transcranial direct current stimulation and transcranial magnetic stimulation. We have provided some suggestions that will help overcome the current limitations in upcoming research.

Non-invasive brain stimulation in modulation of mental rotation ability: A systematic review and meta-analysis.

Mental rotation, the ability to manipulate mental images, is an important function in human cognition. This systematic review and meta-analysis investigates the potential of non-invasive brain stimulation in modulation of this component of visuo-spatial perception. The PubMed database was reviewed prior to 31 September 2020 on randomized controlled trials investigating the effects of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and transcranial alternating current stimulation (tACS) on the mental rotation ability in healthy persons. A total of 17 studies (including 485 subjects) matched our inclusion criteria. Within their scope, overall, 46 sham-controlled experiments were performed. Methodology and results of each experiment are presented in a meta-analysis. The data show a large variety of methods and effects. The influence of (1) stimulation-technique (tDCS, tACS, and rTMS), (2) stimulation protocol (anodal, cathodal, bilateral tDCS, tACS, high-frequency rTMS, low-frequency rTMS, paired pulse rTMS, and theta burst stimulation), (3) stimulation timing (preconditioning and simultaneous), (4) stimulation location (left, right hemisphere, frontal, and parietal area), and (5) stimulus type (bodily and non-bodily) is discussed. The data indicate a beneficial effect of anodal tDCS and of tACS and no effect of cathodal tDCS on the mental rotation ability. Bilateral tDCS protocols both improved and worsened the parameters assessed. The small effect sizes obtained in mostly rTMS experiments require cautious interpretation.

The Effect of Non-Invasive Brain Stimulation (NIBS) on Executive Functioning, Attention and Memory in Rehabilitation Patients with Traumatic Brain Injury: A Systematic Review.

In recent years, the potential of non-invasive brain stimulation (NIBS) for therapeutic effects on cognitive functions has been explored for populations with traumatic brain injury (TBI). However, there is no systematic NIBS review of TBI cognitive impairment with a focus on stimulation sites and stimulation parameters. The purpose of this study was to conduct a systematic review examining the effectiveness and safety of NIBS for cognitive impairment after a TBI. This study was prospectively registered with the PROSPERO database of systematic reviews (CRD42020183298). All English articles from the following databases were searched from inception up to 31 December 2020: Pubmed/MEDLINE, Scopus, CINAHL, Embase, PsycINFO and CENTRAL. Randomized and prospective controlled trials, including cross-over studies, were included for analysis. Studies with at least five individuals with TBI, whereby at least five sessions of NIBS were provided and used standardized neuropsychological measurement of cognition, were included. A total of five studies met eligibility criteria. Two studies used repetitive transcranial magnetic stimulation (rTMS) and three studies used transcranial direct current stimulation (tDCS). The pooled sample size was 44 individuals for rTMS and 91 for tDCS. Three of five studies combined cognitive training or additional therapy (computer assisted) with NIBS. Regarding rTMS, target symptoms included attention (n = 2), memory (n = 1), and executive function (n = 2); only one study showing significant improvement compared than control group with respect to attention. In tDCS studies, target symptoms included cognition (n = 2), attention (n = 3), memory (n = 3), working memory (WM) (n = 3), and executive function (n = 1); two of three studies showed significant improvement compared to the control group with respect to attention and memory. The evidence for NIBS effectiveness in rehabilitation of cognitive function in TBI is still in its infancy, more studies are needed. In all studies, dorsolateral prefrontal cortex (DLPFC) was selected as the stimulation site, along with the stimulation pattern promoting the activation of the left DLPFC. In some studies, there was a significant improvement compared to the control group, but neither rTMS nor tDCS had sufficient evidence of effectiveness. To the establishment of evidence we need the evaluation of brain activity at the stimulation site and related areas using neuroimaging on how NIBS acts on the neural network.

The Effect of Non-Invasive Brain Stimulation (NIBS) on Attention and Memory Function in Stroke Rehabilitation Patients: A Systematic Review and Meta-Analysis.

Background: In recent years, the potential of non-invasive brain stimulation (NIBS) for therapeutic effects on cognitive functions has been explored for populations with stroke. There are various NIBS methods depending on the stimulation site and stimulation parameters. However, there is no systematic NIBS review of post-stroke cognitive impairment with a focus on stimulation sites and stimulation parameters. The purpose of this study is to conduct a systematic review and meta-analysis on effectiveness and safety of NIBS for cognitive impairment after a stroke to obtain new insights. This study was prospectively registered with the PROSPERO database of systematic reviews (CRD42020183298). Methods: All English articles from MEDLINE, Scopus, CINAHL, Embase, PsycINFO, and CENTRAL were searched from inception up to 31 December 2020. Randomized and prospective controlled trials were included for the analysis. Studies with at least five individuals post-stroke, whereby at least five sessions of NIBS were provided and using standardized neuropsychological measurement of cognition, were included. We assessed the methodological quality of selected studies as described in the Physiotherapy Evidence Database (PEDro) scoring system. Results: A total of 10 studies met eligibility criteria. Six studies used repetitive transcranial magnetic stimulation (rTMS) and four studies used transcranial direct current stimulation (tDCS). The pooled sample size was 221 and 196 individuals who received rTMS and tDCS respectively. Eight studies combined general rehabilitation, cognitive training, or additional therapy with NIBS. In rTMS studies, target symptoms included global cognition (n = 4), attention (n = 3), memory (n = 4), working memory (WM) (n = 3), and executive function (n = 2). Five studies selected the left dorsolateral prefrontal cortex (DPLFC) as the stimulation target. One rTMS study selected the right DLPFC as the inhibitory stimulation target. Four of six studies showed significant improvement. In tDCS studies, target symptoms included global cognition (n = 2), attention (n = 4), memory (n = 2) and WM (n = 2). Three studies selected the frontal area as the stimulation target. All studies showed significant improvement. In the meta-analysis, rTMS showed a significant effect on attention, memory, WM and global cognition classified by neuropsychological tests. On the other hand, tDCS had no significant effect. Conclusions: In post-stroke patients with deficits in cognitive function, including attention, memory, and WM, NIBS shows promising positive effects. However, this effect is limited, suggesting that further studies are needed with more precision in stimulation sites and stimulation parameters. Future studies using advanced neurophysiological and neuroimaging tools to allow for a network-based approach to treat cognitive symptoms post-stroke with NIBS are warranted.

Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations

BackgroundNon-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. ObjectiveTo determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. MethodsA non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single- and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. ResultsOver 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8–18.0). Populations included typical development (n = 118), perinatal stroke/cerebral palsy (n = 101), mild traumatic brain injury (n = 121) neuropsychiatric disorders (n = 37), and other (n = 7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. ConclusionsStandard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included.

Intensity Matters: High-intensity Interval Exercise Enhances Motor Cortex Plasticity More Than Moderate Exercise.

A single bout of cardiovascular exercise can enhance plasticity in human cortex; however, the intensity required for optimal enhancement is debated. We investigated the effect of exercise intensity on motor cortex synaptic plasticity, using transcranial magnetic stimulation. Twenty healthy adults (Mage = 35.10 ± 13.25 years) completed three sessions. Measures of cortico-motor excitability (CME) and inhibition were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). Results showed that high-intensity interval exercise enhanced iTBS plasticity more than rest, evidenced by increased CME and intracortical facilitation, and reduced intracortical inhibition. In comparison, the effect of moderate-intensity exercise was intermediate between high-intensity exercise and rest. Importantly, analysis of each participant's plasticity response profile indicated that high-intensity exercise increased the likelihood of a facilitatory response to iTBS. We also established that the brain-derived neurotrophic factor Val66Met polymorphism attenuated plasticity responses following high-intensity exercise. These findings suggest that high-intensity interval exercise should be considered not only when planning exercise interventions designed to enhance neuroplasticity, but also to maximize the therapeutic potential of non-invasive brain stimulation. Additionally, genetic profiling may enhance efficacy of exercise interventions for brain health.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty.

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Chapter 26 - Noninvasive stimulation

The cerebellum plays a fundamental role in movement execution and motor control in humans. Because of multiple cerebellar connections and a broad variety of motor and nonmotor functions, the field of cerebellar stimulation with noninvasive techniques has gained success among researchers in the last few years. These techniques allow investigation of the neural network noninvasively, collecting more information on cerebellar physiology and pathophysiology. Several studies have highlighted the therapeutic potential of noninvasive brain stimulation (NIBS) - repetitive transcranial magnetic stimulation and transcranial direct current stimulation of the brain - in patients with neurologic diseases. More recently, NIBS has been delivered over the human cerebellum. Cerebellar NIBS has provided interesting novel data about cerebellar physiology in humans, especially in relation to its cognitive and behavioral functions. Cerebellar NIBS is also increasingly tested in patients with ataxia, dystonia, Parkinson disease, stroke, and essential tremor. NIBS is a promising approach not only to elucidate the numerous cerebellar functions, but also to improve the management of cerebellar ataxias in children and in adults.

Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease.

Alzheimer's disease (AD) is a looming public health crisis that currently lacks an effective treatment. Noninvasive Brain Stimulation (NBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offers a promising alternative approach to pharmacological interventions for an increasing number of neurological and psychiatric conditions. The aim of this review is summarize data from therapeutic trials of NBS in AD and other dementing illnesses. Despite the potential of NBS, there is limited theoretical framework and a lack of guidelines for its applications to AD. Several published clinical trials failed to report key parameters of the interventions thus limiting the utility of the study to assess efficacy and safety. Our review concludes with some suggestions for future studies aimed to advance research into NBS as a potential treatment for the symptoms and disabilities caused by AD and to enable comparison of results across trials. Ultimately, appropriately powered, and controlled, multi-site randomized clinical trials will be needed to evaluate the therapeutic potential of NBS in AD.

Variability in neural excitability and plasticity induction in the human cortex: A brain stimulation study

BackgroundThe potential of non-invasive brain stimulation (NIBS) for both probing human neuroplasticity and the induction of functionally relevant neuroplastic change has received significant interest. However, at present the utility of NIBS is limited due to high response variability. One reason for this response variability is that NIBS targets a diffuse cortical population and the net outcome to stimulation depends on the relative levels of excitability in each population. There is evidence that the relative excitability of complex oligosynaptic circuits (late I-wave circuits) as assessed by transcranial magnetic stimulation (TMS) is useful in predicting NIBS response. ObjectiveHere we examined whether an additional marker of cortical excitability, MEP amplitude variability, could provide additional insights into response variability following application of the continuous theta burst stimulation (cTBS) NIBS protocol. Additionally we investigated whether I-wave recruitment was associated with MEP variability. MethodsThirty-four healthy subjects (15 male, aged 18–35 years) participated in two experiments. Experiment 1 investigated baseline MEP variability and cTBS response. Experiment 2 determined if I-wave recruitment was associated with MEP variability. ResultsData show that both baseline MEP variability and late I-wave recruitment are associated with cTBS response, but were independent of each other; together, these variables predict 31% of the variability in cTBS response. ConclusionsThis study provides insight into the physiological mechanisms underpinning NIBS plasticity responses and may facilitate development of more reliable NIBS protocols.

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 RehabilitationDespite extensive rehabilitation some amputees continue to experience difficulty with prosthetic mobilityBrain reorganisation following amputation has been related to functional outcomes and may be an appropriate target for novel interventionsNon-invasive brain stimulation is a promising tool which has potential to improve functional outcomes for lower limb amputees

Inter- and intra-subject variability of motor cortex plasticity following continuous theta-burst stimulation.

The potential of non-invasive brain stimulation (NIBS) for studying, and inducing, functionally relevant neuroplasticity is dependent on protocols that can induce lasting, robust and reliable effects. A current limiting factor is the large inter- and intra-subject variability in NIBS-induced neuroplastic responses. There has been some study of inter-subject response variability and factors that contribute to it; however, intra-subject response variability has, so far, received little investigation. By testing participants on multiple occasions we aimed to (1) compare inter- and intra-subject variability of neuroplastic responses induced by continuous theta-burst stimulation (cTBS); (2) determine whether the transcranial magnetic stimulation (TMS) intensity used to measure cTBS-induced neuroplastic responses contributes to response variability; (3) determine whether assessment of factors known to influence response variability can be used to explain some of the variability in cTBS-induced neuroplastic responses across experimental sessions. In three separate experimental sessions, motor-evoked potential (MEP) input-output (IO) curves were obtained before and after cTBS, and questionnaire-based assessments of physical activity and perceived stress were obtained. cTBS-induced MEP suppression was greatest at the upper end of the IO curve (150-180% resting motor threshold; RMT) and most consistent across subjects and across experimental sessions when assessed with a TMS intensity of 150% RMT. The magnitude of cTBS-induced MEP suppression evoked at 150% RMT correlated with self-reported perceived stress, but not with self-reported physical activity. The most reliable TMS intensity to probe cTBS-induced long-term depression (LTD)-like neuroplastic responses is 150% RMT. This is unlikely to simply be a ceiling effect and, we suggest, may be due to changes in the descending volley evoked at higher stimulus intensities. The perceived stress scale appears to be sufficiently sensitive to measure the influence of subject stress on LTD-like neuroplastic responses.

Modulation of brain plasticity in stroke: a novel model for neurorehabilitation.

Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model--which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies--is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance-recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.