- •This study uses a systematic, bibliometric approach to assess the TMS literature base.
- •Annual TMS research output has increased dramatically over the period 1988–2017.
- •The top disease entities studied to date have been stroke and depression.
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulatory technique that has broad diagnostic and therapeutic potential across a range of neurological and psychiatric diseases.
This study utilises a bibliometric approach to systematically and comprehensively evaluate the literature on TMS from the last three decades.
The Scopus citation database was used to identify all peer-reviewed journal articles concerning TMS over the period 1988–2017. Frequency-distribution, cross-tabulation and keyword analyses were performed to determine the most prolific researchers, institutions, nations, journals and the foremost studied disease entities within the TMS field. Given recent heightened awareness of gender bias across many fields of biomedicine, female representation among the most prolific authors was determined. Open-access publication rates and types of study design utilised were also quantified.
17,492 TMS-related articles were published during the study period 1988–2017. The annual TMS research output has increased dramatically over this time, despite a recent levelling-off of publications per year. The most prolific institutions were based in the United Kingdom, the United States and Canada. The top disease entities studied were stroke, depression and Parkinson’s disease. Only 4/52 of the most productive researchers during the study period were female. A minority (4.81%) of publications were published as gold open-access.
This study implemented a systematic, bibliometric approach to quantitively assess the breadth of the TMS literature base and identify temporal publication and authorship trends. Drawing on these insights may aid understanding of historical progress in TMS over the last 30 years and help identify into unmet needs and opportunities to improve scientific and publishing practices to contribute to the future health of the field. These findings are likely to be relevant to researchers, clinicians, funders, industry collaborators and other stakeholders.
There is a claim that improvements in motor function in people with stroke following constraint-induced movement therapy (CIMT) is due to compensation but not actually neurorestoration. However, few studies have demonstrated improvements in neurophysiological outcomes such as increased motor map size and activation of primary cortex, or their positive correlations with motor function, following CIMT. The aim of this study was to carry out a systematic review of CIMT trials using neurophysiological outcomes, and a meta-analysis of the relationship between the neurophysiological outcomes and motor function.
Editorial on the Research Topic
The Oxford dictionary defines the term priming as “a substance that prepares something for use or action.” In this special issue, we define motor priming as a technique, experience, or activity targeting the motor cortex resulting in subsequent changes in motor behavior. Inadequate functional recovery after neural damage is a persisting burden for many, and this insufficiency highlights the need for new neurorehabilitation paradigms that facilitate the capacity of the brain to learn and recover. The concept of motor priming has gained importance in the last decade. Numerous motor priming paradigms have emerged to demonstrate success to improve functional recovery after injury. Some of the successful priming paradigms that have shown to alter motor behavior and are easily implementable in clinical practice include non-invasive brain stimulation, movement priming, motor imagery, and sensory priming. The full clinical impact of these priming paradigms has not yet been realized due to limited evidence regarding neural mechanisms, safety and effectiveness, dosage, individualization of parameters, identification of the appropriate therapies that need to be provided in combination with the priming technique, and the vital time window to maximize the effectiveness of priming. In this special issue, four manuscripts address critical questions that will enhance our understanding of motor priming paradigms and attempt to bridge the gap between neurophysiology and clinical implementation.
In their study, “Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site,” Harris-Love and Harrington elegantly address the extremely important issue of individualizing brain stimulation for upper limb stroke recovery. Many brain stimulation techniques show high interindividual variability and low reliability as the “one-size-for-all” does not fit the vast heterogeneity in recovery observed in stroke survivors. In this article, the authors propose a novel framework that personalizes the application of non-invasive brain stimulation based on understanding of the structural anatomy, neural connectivity, and task attributes. They further provide experimental support for this idea with data from severely impaired stroke survivors that validate the proposed framework.
The issue of heterogeneity poststroke is also addressed by Lefebvre and Liew in “Anatomical Parameters of tDCS to modulate the motor system after stroke: A review.” These authors discuss the variability in research using tDCS for the poststroke population. According to the authors, the most likely sources of variability include the heterogeneity of poststroke populations and the experimental paradigms. Individually based variability of results could be related to various factors including: (1) molecular factors such as baseline measures of GABA, levels of dopamine receptor activity, and propensity of brain-derived neurotropic factor expression; (2) time poststroke, (3) lesion location; (4) type of stroke; and (5) level of poststroke motor impairment. Variability related to experimental paradigms include the timing of the stimulation (pre- or post-training), the experimental task, and whether the protocol emphasizes motor performance (a temporary change in motor ability) or motor learning based (more permanent change in motor ability). Finally, the numerous possibilities of electrode placement, neural targets, and the different setups (monocephalic versus bi-hemispheric) add further complexity. For future work with the poststroke population, the authors suggest that tDCS experimental paradigms explore individualized neural targets determined by neuronavigation.
In another exciting study in this issue, Estes et al. tackle the timely topic of spinal reflex excitability modulated by motor priming in individuals with spinal cord injury. The authors choose to test four non-pharmacological interventions: stretching, continuous passive motion, transcranial direct current stimulation, and transcutaneous spinal cord stimulation to reduce spasticity. Three out of four techniques were associated with reduction in spasticity immediately after treatment, to an extent comparable to pharmacological approaches. These priming approaches provide a low-cost and low-risk alternative to anti-spasticity medications.
In another clinical study in individuals with spinal cord injury, Gomes-Osman et al. examined effects of two different approaches to priming. Participants were randomized to either peripheral nerve stimulation (PNS) plus functional task practice, PNS alone, or conventional exercise therapy. The findings were unexpected. There was no change in somatosensory function or power grip strength in any of the groups. Interestingly, all of the interventions produced changes in precision grip of the weaker hand following training. However, only PNS plus functional task practice improved precision grip in both hands. The authors found that baseline corticospinal excitability were significantly correlated to changes in precision grip strength of the weaker hand. The lack of change in grip strength in any of the groups was surprising. Previous evidence suggests, however, that the corticomotor system is more strongly activated during precision grip as compared to power grip, and the authors suggest that interventions targeting the corticomotor system (i.e., various priming methods) may more strongly effect precision grip.
Overall, this special issue brings together an array of original research articles and reviews that further enhance our understanding of motor priming for motor recovery with an emphasis on neural mechanisms and clinical implementation. We hope that the studies presented encourage future studies on motor priming paradigms to optimize the potential for functional recovery in the neurologically disadvantaged population, and further our understanding of neuroplasticity after injury.
SM and MS have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
SM is supported by funding from the National Institutes of Health (R01HD075777).
July 19, 2017
The number of available anti-seizure medications has exploded in the past two decades, going from just a handful of medicines available in the 1990s to more than 20 now. Once the Food and Drug Administration (FDA) approves each new medicine based on trials in adults, it’s available for clinicians to prescribe off-label to all age groups. However, says William D. Gaillard, M.D., division chief of Child Neurology and Epilepsy, Neurophysiology and Critical Care Neurology at Children’s National Health System, trials that lead to FDA approval for adults do not provide any information about which medications are best for children.
“With so many medications and so little data,” Dr. Gaillard says, “one might think doctors would choose a wider variety of medicines when they prescribe to children with epilepsy.”
However, the results from a recent study by Dr. Gaillard and colleagues, published online in Pediatric Neurology on June 27, 2017, show otherwise. The study indicates that doctors in the United States appear to have reached an unexpected consensus about which medication to prescribe for their pediatric patients.
The study is part of a broader effort to collect data on the youngest epilepsy patients — those younger than 3 years old, the age at which epilepsy most often becomes evident. As part of this endeavor, researchers from 17 U.S. pediatric epilepsy centers enrolled in the study 495 children younger than 36 months old who had been newly diagnosed with non-syndromic epilepsy (a condition not linked to any of the commonly recognized genetic epilepsy syndromes).
The researchers mined these patients’ electronic medical records for information about their demographics, disease and treatments. About half of the study participants were younger than 1 year old when they were diagnosed with epilepsy. About half had disease marked by focal features, meaning that their epilepsy appeared to originate from a particular place in the brain. Nearly all were treated with a single medication, as opposed to a cocktail of multiple medicines.
Of those treated with a single medication, nearly all were treated with one of five medicines: Levetiracetam, oxcarbazepine, phenobarbital, topiramate and zonisamide. However, the data showed a clear prescribing preference. About 63 percent of the patients were prescribed levetiracetam as a first choice. By contrast, oxcarbazepine and phenobarbital, the next most frequently prescribed medicines, were taken by patients as a first choice by a mere 14 percent and 13 percent respectively.
Even more striking, of the children who were not prescribed levetiracetam initially but required a second medication due to inadequate efficacy or unacceptable side effects, 62 percent also received this medication. That made levetiracetam the first or second choice for about 74 percent of all the children in the study, despite the availability of more than 20 anti-seizure medications.
It’s not clear why levetiracetam is such a frequent choice in the United States, says Dr. Gaillard. However, in its favor, the drug is available in a liquid formulation, causes no ill effects medically and can be started intravenously if necessary. Studies have shown that it appears to be effective in controlling seizures in about 40 percent of infants.
Yet, levetiracetam’s market dominance appears to be a North American phenomenon, the study authors write. A recent international survey that Dr. Gaillard also participated in suggests that outside of this continent, carbazepine and oxcarbazepine were the most frequently prescribed medications to treat focal seizures.
What’s really necessary, Dr. Gaillard says, is real data on efficacy for each of the medications commonly prescribed to pediatric epilepsy patients–a marked vacuum in research that prevents doctors from using evidence-based reasoning when making medication choices.
“This study identifies current practices, but whether those practices are correct is a separate question,” he explains. “Just because a medication is used commonly doesn’t mean it is the best medication we should be using.”
To answer that question, he says, researchers will need to perform a head-to-head clinical trial comparing the top available epilepsy medications in children. This study sets the stage for such a trial by identifying which medications should be included.
“Uncontrolled pediatric epilepsy can have serious consequences, from potential problems in development to a higher risk of death,” Dr. Gaillard says. “You want to use the optimal medicine to treat the disease.”
Stroke can lead to motor impairments that can affect the body structure and restraint mobility. We hypothesize that brain lesions and their motor sequelae can distort the body schema, a sensorimotor map of body parts and elements in the peripersonal space through which human beings embody the reachable space and ready the body for forthcoming movements. Two main constructs have been identified in the embodiment mechanism: body-ownership, the sense that the body that one inhabits is his/her own, and agency, the sense that one can move and control his/her body. To test this, the present study simultaneously investigated different embodiment subcomponents (body-ownership, localization, and agency) and different neurophysiological measures (galvanic skin response, skin temperature, and surface electromyographic activity), and the interaction between them, in clinically-controlled hemiparetic individuals with stroke and in healthy subjects after the rubber hand illusion. Individuals with stroke reported significantly stronger body-ownership and agency and reduced increase of galvanic skin response, skin temperature, and muscular activity in the stimulated hand. We suggest that differences in embodiment could have been motivated by increased plasticity of the body schema and pathological predominance of the visual input over proprioception. We also suggest that differences in neurophysiological responses could have been promoted by a suppression of the reflex activity of the sympathetic nervous system and by the involvement of the premotor cortex in the reconfiguration of the body schema. These results could evidence a body schema plasticity promoted by the brain lesion and a main role of the premotor cortex in this mechanism.
This single volume brings together both theoretical developments in the field of motor control and their translation into such fields as movement disorders, motor rehabilitation, robotics, prosthetics, brain-machine interface, and skill learning. Motor control has established itself as an area of scientific research characterized by a multi-disciplinary approach. Its goal is to promote cooperation and mutual understanding among researchers addressing different aspects of the complex phenomenon of motor coordination. Topics covered include recent theoretical advances from various fields, the neurophysiology of complex natural movements, the equilibrium-point hypothesis, motor learning of skilled behaviors, the effects of age, brain injury, or systemic disorders such as Parkinson’s Disease, and brain-computer interfaces.
Despite current standard rehabilitation efforts, walking deficits that contribute to limitations in activity and participation in individuals with chronic stroke persist.
Recent developments in a noninvasive brain stimulation technology, transcranial magnetic stimulation (TMS), provide an opportunity to investigate neurophysiologic components underlying post-stroke motor recovery by quantifying the strength of corticomotor connectivity to specific muscles. There is evidence that the balance of corticomotor drive to paretic and nonparetic upper extremities of stroke survivors is related to motor function, can be changed through rehabilitation, and can predict functional outcomes in response to intervention.
However, neurophysiologic mechanisms underlying lower extremity motor recovery are unknown and our understanding of rehabilitation effects on cortical factors that could influence post-stroke walking ability is poor.
The overall purpose of this project was to investigate corticomotor factors underlying lower extremity clinical (aim 1) and biomechanical (aim 2) walking function following stroke. Additionally, we sought to determine the effectiveness of a single session of rehabilitation utilizing gait training with functional electrical stimulation (FES) to induce changes in corticomotor behavior that, if improved, could promote positive changes in biomechanical walking impairments (aim 3).
The results of this study indicate that balance of corticomotor drive to the paretic and nonparetic lower extremities is critical to the level of walking function achieved by individuals with chronic stroke. Our results suggest that both the lesioned and nonlesioned motor cortices play a role in post-stroke walking recovery. This can be evidenced by the origins of corticomotor asymmetry stemming from both reduced corticomotor drive to the paretic leg and enhanced corticomotor drive to the nonparetic leg in stroke survivors with poor walking recovery. These patterns of corticomotor asymmetry are different between resting and active motor states and more severely affect the ankle plantarflexor muscles than the dorsiflexor muscles. The balance of corticomotor drive between limbs affected post-stroke walking biomechanical function, as we found that corticomotor symmetry to plantarflexor muscles determined the propulsive strategy that stroke survivors used to achieve their fastest walking speeds.
Critically, findings of this project further demonstrated that a single session of gait rehabilitation utilizing FES could promote corticomotor balance to plantarflexors that was positively related to improvements in biomechanical gait impairments.
Together, these findings offer new insights into neurophysiologic mechanisms underlying post-stroke walking ability and identify specific cortical mechanisms that may be targeted through rehabilitation to produce positive changes in biomechanical walking function in stroke survivors.
According to a prevailing view, the visual system works by dissecting stimuli into primitives, whereas the auditory system processes simple and complex stimuli with their corresponding features in parallel. This makes musical stimulation particularly suitable for patients with disorders of consciousness (DoC), because the processing pathways related to complex stimulus features can be preserved even when those related to simple features are no longer available. An additional factor speaking in favor of musical stimulation in DoC is the low efficiency of visual stimulation due to prevalent maladies of vision or gaze fixation in DoC patients. Hearing disorders, in contrast, are much less frequent in DoC, which allows us to use auditory stimulation at various levels of complexity.
The current paper overviews empirical data concerning the four main domains of brain functioning in DoC patients that musical stimulation can address: perception (e.g., pitch, timbre, and harmony), cognition (e.g., musical syntax and meaning), emotions, and motor functions. Music can approach basic levels of patients’ self-consciousness, which may even exist when all higher-level cognitions are lost, whereas music induced emotions and rhythmic stimulation can affect the dopaminergic reward-system and activity in the motor system respectively, thus serving as a starting point for rehabilitation.
The electrically-evoked afferent volley generated during NeuroMuscular Electrical Stimulation (NMES) can increase the excitability of CorticoSpinal (CS) pathways. Over time, NMES can strengthen damaged CS pathways and result in enduring improvements in function for persons with central nervous system injury or disease. NMES-induced increases in CS excitability have been studied using a variety of NMES parameters, yet the influence of these stimulation parameters on increasing CS excitability is not well understood.
NMES is commonly delivered at intensities sufficient to generate repeated functional contractions for relatively short durations (30-40 min) or at low intensities, near motor threshold, for long durations (2 h).
For the purpose of this study, these different stimulation protocols are termed Functional Electrical Stimulation (FES) and Somatosensory Stimulation (SS), respectively. A direct comparison of increases in CS excitability induced by such protocols has not been conducted. Thus, the present experiments were designed to compare changes in CS excitability for Abductor Pollicis Brevis (APB) in the hand following FES and SS of the median nerve.
We hypothesized that due to the generation of a larger afferent volley, the FES would increase CS excitability more than the SS. Ten Motor Evoked Potentials (MEPs) were evoked in APB using transcranial magnetic stimulation before and after each type of NMES. MEP amplitude increased significantly following both the FES (by 66 ± 7%, mean ± standard error) and SS (49 ± 6%), but the amplitude of these increases was not significantly different.
These results suggest that just 40 min of FES can increase CS excitability, and potentially provide rehabilitative benefits, to the same extent as 2 h of SS.