The effect of magnetic coil orientation on the excitation of the median nere

Objective – We investigated the effect of magnetic coil orientation on the excitation of the median nerve in healthy subjects. Methods – An 8-shaped coil, 3.2 cm in outer diameter, was used. The median nerve was stimulated at the elbow while the compound muscle action potentials (CMAPs) of abductor pollicis brevis muscle were recorded at 4 different directions of the induced current: orthodromic, antidromic, medio-lateral and latero-medial. Results – We found that the amplitude of the CMAP was the greatest in a medio-lateral (ML) direction. We also measured the induced electric field in the saline tank that mimicked the forearm. The induced electric field and its spatial gradient were the greatest in the ML direction among 4 directions. Conclusion – The fact that the forearm is a restrictive volume conductor may result in the different effects of coil orientation on the excitation of the median nerve at the elbow.     

Normal cortical excitability in Myoclonus-Dystonia — A TMS study

Objective

The aim of the present study is to investigate cortical excitability in patients with DYT 11 positive Myoclonus-Dystonia (M-D), using transcranial magnetic stimulation (TMS).

Methods

Silent period, motor evoked potential (MEP) recruitment curve, short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and short interval intracortical facilitation (SICF), with short interstimulus intervals (ISIs) ranging from 1.2 to 3.2 ms, were studied in 15 DYT 11-positive M–D patients and their matched controls. In four patients and matched controls peripheral double pulse electrical nerve stimulation was performed.

Results

All TMS parameters of cortical excitability were normal compared to healthy controls. In the SICF protocol we observed more variable and polyphasic MEPs in M–D patients. Cross-covariance analysis of MEP area revealed a significant correlation difference at ISI 2.2 and 2.8 ms. This increased variability was not seen in other TMS protocols or with peripheral nerve stimulation.

Conclusions

In contrast with other types of dystonia, no changes in cortical excitability were found in DYT 11 patients. Our findings suggest that M–D is both clinically and pathophysiologically a separate entity from other dystonic disorders. Polyphasic MEPs during the SICF protocol in M–D patients could reflect central neuron membrane instability. Application of the SICF protocol in other patient groups has to prove its value in movement disorders.     

Database of 25 validated coil models for electric field simulations for TMS

BackgroundThe effects of transcranial magnetic stimulation (TMS) on brain activity depend on the design of the stimulation coil. A wide range of coils from different vendors are currently used with different stimulation properties. This decreases the comparability of study results.ObjectiveTo systematically compare widely used commercial TMS coils concerning their focality, stimulation depth and efficacy. To provide validated models and data of these coils for accurate simulations of the induced electric fields.MethodsWe reconstructed the magnetic vector potential of 25 commercially available TMS coils of different vendors from measurements of their magnetic fields. Most coils had a figure-of-eight configuration. We employed the reconstructed magnetic vector potential in simulations of the electric field in a spherical head model. We estimated the motor thresholds of the coil-stimulator combinations using the calculated fields, the pulse waveforms and a leaky integrator model of the neural membrane.ResultsOur results confirm a previously reported systematic trade-off between focality and relative depth of stimulation. However, neither the peak field strength in the “cortex” of the sphere model nor the estimated motor thresholds were strongly related to the two former measures and need to be additionally determined.ConclusionOur comprehensive coil characterization facilitates objective comparisons of coils of different sizes and from different vendors. The models and auxiliary data will be made available for electric field simulations in SimNIBS. Our work will support TMS users making an informed selection of a suited coil for a specific application and will help to reduce uncertainty regarding the TMS-induced electric field in the brain target region.     

Significance of magnetic coil position in peripheral motor nerve stimulation

The influences of coil position and coil-nerve distance on compound muscle action potentials (CMAPs), recorded from the first dorsal interosseus muscle during magnetic stimulation of the brachial segment of the ulnar nerve, were studied in 10 healthy volunteers. A 14-cm coil was held tangentially to the skin with the center overlying the nerve. Mapping of the CMAP latencies and amplitudes was made as the coil was displaced laterally in steps of 1 cm and in planes 0-3 cm from the skin surface. Stimulation with the coil center positioned 3 cm laterally to the nerve with the coil current directed proximally yielded the largest amplitudes with minimal variability and the most constant relationship to electrically evoked CMAPs. In this position the interindividual and intraindividual reproducibility of the magnetically evoked latencies were at least as good as those of electric stimulation when coil-skin distance was less than or equal to 2 cm.     

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic

BackgroundThe COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19.ObjectiveTo facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS).MethodsThe present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research – with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics.ResultsA model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described.ConclusionThere is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.     

Effects of coil orientation and magnetic field shield on transcranial magnetic stimulation in cats

To obtain suitable stimulus conditions for transcranial magnetic stimulation, the evoked compound muscle action potential (ECMAP), evoked spinal cord potential (ESCP), and magnetic and electric fields were analyzed in cats with and without the use of a magnetic field shield. Cats were stimulated using a figure 8 magnetic coil placed on the cranium above the motor cortex. The maximum ECMAP amplitude was recorded when the electric current in the coil was in the mediolateral direction, regardless of whether a magnetic shield with a 5 × 5 cm window was used. ECMAP and ESCP thresholds were reduced when magnetic shielding was in place. Due to the edge effect, the strengths of the magnetic and electric fields were highest in the brainstem area, which is an inhomogeneous volume conductor of the cat's cranium. A large induced electric field directed caudally elicited ECMAP and ESCP responses effectively when a magnetic shield with a 5 × 5 cm window was in place. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1172–1180, 1998.     

The effect of meninges on the electric fields in TES and TMS. Numerical modeling with adaptive mesh refinement

BackgroundWhen modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges – dura, arachnoid, and pia mater – are often neglected due to high computational costs.ObjectiveWe investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model.MethodWe use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas ($\text{M}{1}_{\text{HAND}}$ and $\text{DLPFC}$) and for several distinct TES and TMS setups.ResultsMaximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (～6%) decrease on average when the meninges are included.ConclusionOur results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online.     

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation

BACKGROUND: Reliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons. METHODS: The mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed. RESULTS: In particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells. CONCLUSIONS: We conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.     

Dissociating cognitive from affective theory of mind: A TMS study

Introduction

“Theory of Mind” (ToM), i.e., the ability to infer other persons' mental states, is a key function of social cognition. It is increasingly recognized to form a multidimensional construct. One differentiation that has been proposed is that between cognitive and affective ToM, whose neural correlates remain to be identified. We aimed to ascertain the possible role of the right dorsolateral prefrontal cortex (DLPFC) for cognitive ToM as opposed to affective ToM processes.

Methods

1 Hz repetitive transcranial magnetic stimulation (rTMS) was used to interfere offline with cortical function of the right DLPFC in healthy male subjects who subsequently had to perform a computerized task assessing cognitive and affective ToM.

Results

RTMS over the right DLPFC induced a selective effect on cognitive but not affective ToM. More specifically, a significant acceleration of reaction times in cognitive ToM compared to affective ToM and control items was observed in the experimental (right DLPFC) compared to the control (vertex) rTMS stimulation condition.

Conclusions

Our findings provide evidence for the functional independence of cognitive from affective ToM. Furthermore, they point to an important role of the right DLPFC within neural networks mediating cognitive ToM. Possible underlying mechanisms of the acceleration of cognitive ToM processing under rTMS are discussed.     

Non pharmacological treatment for neuropathic pain: Invasive and non-invasive cortical stimulation

The use of medications in chronic neuropathic pain may be limited with regard to efficacy and tolerance. Therefore, non-pharmacological approaches, using electrical stimulation of the cortex has been proposed as an alternative. First, in the early nineties, surgically-implanted epidural motor cortex stimulation (EMCS) was proven to be effective to relieve refractory neuropathic pain. Later, non-invasive stimulation techniques were found to produce similar analgesic effects, at least by means of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1). Following “high-frequency” rTMS (e.g., stimulation frequency ranging from 5 to 20 Hz) delivered to the precentral gyrus (e.g., M1 region), it is possible to obtain an analgesic effect via the modulation of several remote brain regions involved in nociceptive information processing or control. This pain reduction can last for weeks beyond the time of the stimulation, especially if repeated sessions are performed, probably related to processes of long-term synaptic plasticity. Transcranial direct current stimulation (tDCS), another form of transcranial stimulation, using low-intensity electrical currents, generally delivered by a pair of large electrodes, has also shown some efficacy to improve patients with chronic pain syndromes. The mechanism of action of tDCS differs from that of EMCS and rTMS, but the cortical target is the same, which is M1. Although the level of evidence of therapeutic efficacy in the context of neuropathic pain is lower for tDCS than for rTMS, interesting perspectives are opened by using at-home tDCS protocols for long-term management. Now, there is a scientific basis for recommending both EMCS and rTMS of M1 to treat refractory chronic neuropathic pain, but their application in clinical practice remains limited due to practical and regulatory issues.     

TMS with fast and accurate electronic control: Measuring the orientation sensitivity of corticomotor pathways

BackgroundTranscranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing.ObjectiveWe aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability.MethodsWe designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custom-made electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3° steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude.ResultsThe two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity.ConclusionThe developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols.     

Language mapping in healthy volunteers and brain tumor patients with a novel navigated TMS system: Evidence of tumor-induced plasticity

ObjectiveThis article explores the feasibility of a novel repetitive navigated transcranial magnetic stimulation (rnTMS) system and compares language mapping results obtained by rnTMS in healthy volunteers and brain tumor patients.MethodsFifteen right-handed healthy volunteers and 50 right-handed consecutive patients with left-sided gliomas were examined with a picture-naming task combined with time-locked rnTMS (5–10 Hz and 80–120% resting motor threshold) applied over both hemispheres. Induced errors were classified into four psycholinguistic types and assigned to their respective cortical areas according to the coil position during stimulation.ResultsIn healthy volunteers, language disturbances were almost exclusively induced in the left hemisphere. In patients errors were more frequent and induced at a comparative rate over both hemispheres. Predominantly dysarthric errors were induced in volunteers, whereas semantic errors were most frequent in the patient group.ConclusionThe right hemisphere’s increased sensitivity to rnTMS suggests reorganization in language representation in brain tumor patients.SignificancernTMS is a novel technology for exploring cortical language representation. This study proves the feasibility and safety of rnTMS in patients with brain tumor.     

Concurrent bilateral projection and activation of motor cortices in a patient with congenital mirror movements: A TMS study

Objectives

Mirror movements (MMs) are unintended and unnecessary movements accompanying voluntary activity in homologous muscles on the opposite side of the body, particularly in distal arm muscles. Congenital MMs may be sporadic or familial. Several mechanisms have been proposed to explain persistent congenital MMs. Hypothesis 1 assumes the existence of an ipsilateral corticospinal pathway, and Hypothesis 2 the activation of both motor cortices. We report a new case of congenital mirror movements in a healthy woman.

Methods

Electromyographic recordings and focal transcranial magnetic stimulation (TMS) were used for neurophysiological evaluation.

Results

Voluntary contraction of either abductor pollicis brevis (APB) elicited mirror activation of the other APB. Focal TMS of either M1 elicited motor evoked potential (MEP) of normal latency and amplitude in both resting APB. TMS of the left cortex upon maximal contraction of the right APB and mirror contraction of the left APB produced interhemispheric inhibition (IHI) in the former and silent period (SP) in the later.

Conclusions

The electrophysiological evaluation using transcranial magnetic stimulation provides evidence of the concurrent action of both mechanisms in this patient.

Significance

The combination of more than one hypothesis could be more appropriate for understanding the underlying mechanism in some MM cases.     

Efficacy of repetitive transcranial magnetic stimulation for Tourette syndrome: A systematic review and meta-analysis

Background

While previous studies have investigated the effect of repetitive transcranial magnetic stimulation (rTMS) in treating Tourette syndrome (TS), the results remain inconclusive.

A [17F]-fluoromethane PET/TMS study of effective connectivity

We used transcranial magnetic stimulation (TMS) in combination with positron emission tomography (PET) to investigate the effective connectivity of four cortical regions within the same study. By employing [17F]-[CH3F] ([17F]-fluoromethane) as a radiotracer of blood-flow, we were able to obtain increased sensitivity compared to [15O]-H2O for both cortical and subcortical structures. The brain areas investigated were left primary motor cortex, right primary visual cortex, and left and right prefrontal areas. We found that each site of stimulation yielded a different pattern of activation/deactivation consistent with its anatomical connectivity. Moreover, we found that TMS of prefrontal and motor cortical areas gave rise to trans-synaptic activation of subcortical circuits.     

Plasticity induced by non-invasive transcranial brain stimulation: A position paper

Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. Non-invasive transcranial brain stimulation may modulate cortical excitability outlasting the period of non-invasive transcranial brain stimulation itself from several minutes to more than one hour. Quite a few lines of evidence, including pharmacological, physiological and behavioral studies in humans and animals, suggest that the effects of non-invasive transcranial brain stimulation are produced through effects on synaptic plasticity. However, there is still a need for more direct and conclusive evidence. The fragility and variability of the effects are the major challenges that non-invasive transcranial brain stimulation currently faces. A variety of factors, including biological variation, measurement reproducibility and the neuronal state of the stimulated area, which can be affected by factors such as past and present physical activity, may influence the response to non-invasive transcranial brain stimulation. Work is ongoing to test whether the reliability and consistency of non-invasive transcranial brain stimulation can be improved by controlling or monitoring neuronal state and by optimizing the protocol and timing of stimulation.