Transcranial Magnetic Stimulation In Humans Research Articles

Dissociation of Centrally and Peripherally Induced Transcranial Magnetic Stimulation Effects in Nonhuman Primates.

Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent centrally induced neural mechanisms and peripherally induced sensory costimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging because of the limited spatiotemporal resolution of available noninvasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in a male and a female nonhuman primate (rhesus macaque) to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response curve with stimulation intensity. We further show that stimulation responses are spatially specific. We use several control conditions to dissociate centrally induced neural responses from auditory and somatosensory coactivation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.SIGNIFICANCE STATEMENT Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation method to stimulate the human brain. To advance its utility for clinical applications, a clear understanding of its underlying physiological mechanisms is crucial. Here, we perform invasive electrophysiological recordings in the nonhuman primate brain during TMS, achieving a spatiotemporal precision not available in human EEG experiments. We find that evoked potentials are dose dependent and spatially specific, and can be separated from peripheral stimulation effects. This means that TMS-evoked responses can indicate a direct physiological stimulation response. Our work has important implications for the interpretation of human TMS-EEG recordings and biomarker development.

Contribution of neural circuits tested by transcranial magnetic stimulation in corticomotor control of low back muscle: a systematic review.

Transcranial magnetic stimulation (TMS) is widely used to investigate central nervous system mechanisms underlying motor control. Despite thousands of TMS studies on neurophysiological underpinnings of corticomotor control, a large majority of studies have focused on distal muscles, and little is known about axial muscles (e.g., low back muscles). Yet, differences between corticomotor control of low back and distal muscles (e.g., gross vs. fine motor control) suggest differences in the neural circuits involved. This systematic review of the literature aims at detailing the organisation and neural circuitry underlying corticomotor control of low back muscles tested with TMS in healthy humans. The literature search was performed in four databases (CINAHL, Embase, Medline (Ovid) and Web of science) up to May 2022. Included studies had to use TMS in combination with EMG recording of paraspinal muscles (between T12 and L5) in healthy participants. Weighted average was used to synthesise quantitative study results. Forty-four articles met the selection criteria. TMS studies of low back muscles provided consistent evidence of contralateral and ipsilateral motor evoked potentials (with longer ipsilateral latencies) as well as of short intracortical inhibition/facilitation. However, few or no studies using other paired pulse protocols were found (e.g., long intracortical inhibition, interhemispheric inhibition). In addition, no study explored the interaction between different cortical areas using dual TMS coil protocol (e.g., between primary motor cortex and supplementary motor area). Corticomotor control of low back muscles are distinct from hand muscles. Our main findings suggest: (i) bilateral projections from each single primary motor cortex, for which contralateral and ipsilateral tracts are probably of different nature (contra: monosynaptic; ipsi: oligo/polysynaptic) and (ii) the presence of intracortical inhibitory and excitatory circuits in M1 influencing the excitability of the contralateral corticospinal cells projecting to low back muscles. Understanding of these mechanisms are important for improving the understanding of neuromuscular function of low back muscles and to improve the management of clinical populations (e.g., low back pain, stroke).

Adrenomedullary responses to non-invasive cortical stimulation in humans

Abstract Introduction: The discovery of cortical adrenomedullary projections in cebus monkeys suggests that similar pathways exist in humans. Notably, the major corticoadrenomedullary projection regions have human equivalents that can be stimulated non-invasively with repetitive transcranial magnetic stimulation (rTMS). If rTMS can be used to selectively modulate adrenomedullary activity, there may be significant therapeutic benefits for stress-, affective-, or neuroimmune-related disorders. Purpose: To assess resting and stress-induced adrenomedullary neuroendocrine responses to continuous (cTBS) and intermittent (iTBS) theta burst TMS in humans. Methods: 39 healthy young adults (14W) were randomly assigned to three counterbalanced sessions of iTBS (n=19) or cTBS (n=20). Stimulation was applied to motor cortical areas that contain the majority of adrenomedullary projections in non-human primates (primary motor cortex trunk region (M1TRUNK) and presupplementary motor area (preSMA)). The M1 leg region (M1LEG) was used as a spatial control. Stimulation locations were determined based on TMS-evoked electromyographic responses in the rectus abdominus (M1TRUNK) and vastus lateralis (M1LEG) or using a combination of fMRI activity and metanalytical structural coordinates (preSMA). All TMS procedures were performed with a 96mm curved double coil and stereotactic navigation. TBS was applied as 600 biphasic TMS pulses at 80% AMT. Corticoadrenomedullary activity and corticospinal excitability (CSE) were assayed before and after TBS, immediately after maximal exercise, and 60min and 90min after TBS based on plasma epinephrine concentrations and median MEP AUC, respectively. Initial analysis of adrenomedullary responses to rTMS were made with a 2 (protocol) x 3 (visit) x 5 (time-point) mixed methods ANOVA. Results and Conclusions: As expected, exercise resulted in a large epinephrine increase (p<0.0001, 8-fold) overall. Ongoing analysis indicates that target-specific changes in adrenomedullary activity are likely, and similar to CSE, may often be paradoxical. Our preliminary results also suggest that adrenomedullary responses to subthreshold rTMS are principally stress inducible. Research Category and Technology and Methods Translational Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Adrenal Medulla, Cortex, Sympathetic Nervous System, Non-Invasive Brain Stimulation

Computational Modeling of Information Propagation during the Sleep-Waking Cycle.

Simple SummaryDuring the deep phases of sleep we do not normally wake up by a thunder, but we nevertheless notice it when awake. The exact same sound gets to our ears and cortex through the thalamus and still, it triggers two very different responses. There is growing experimental evidence that these two states of the brain—sleep and wakefulness—distribute sensory information in different ways across the cortex. In particular, during sleep, neuronal responses remain local and do not spread out across distant synaptically connected regions. On the contrary, during wakefulness, stimuli are able to elicit a wider spatial response. We have used a computational model of coupled cortical columns to study how these two propagation modes arise. Moreover, the transition from sleep-like to waking-like dynamics occurs in agreement with the synaptic homeostasis hypothesis and only requires the increase of excitatory conductances. We have found that, in order to reproduce the aforementioned observations, this parameter change has to be selectively applied: synaptic conductances between distinct columns have to be potentiated over local ones.Non-threatening familiar sounds can go unnoticed during sleep despite the fact that they enter our brain by exciting the auditory nerves. Extracellular cortical recordings in the primary auditory cortex of rodents show that an increase in firing rate in response to pure tones during deep phases of sleep is comparable to those evoked during wakefulness. This result challenges the hypothesis that during sleep cortical responses are weakened through thalamic gating. An alternative explanation comes from the observation that the spatiotemporal spread of the evoked activity by transcranial magnetic stimulation in humans is reduced during non-rapid eye movement (NREM) sleep as compared to the wider propagation to other cortical regions during wakefulness. Thus, cortical responses during NREM sleep remain local and the stimulus only reaches nearby neuronal populations. We aim at understanding how this behavior emerges in the brain as it spontaneously shifts between NREM sleep and wakefulness. To do so, we have used a computational neural-mass model to reproduce the dynamics of the sensory auditory cortex and corresponding local field potentials in these two brain states. Following the synaptic homeostasis hypothesis, an increase in a single parameter, namely the excitatory conductance , allows us to place the model from NREM sleep into wakefulness. In agreement with the experimental results, the endogenous dynamics during NREM sleep produces a comparable, even higher, response to excitatory inputs to the ones during wakefulness. We have extended the model to two bidirectionally connected cortical columns and have quantified the propagation of an excitatory input as a function of their coupling. We have found that the general increase in all conductances of the cortical excitatory synapses that drive the system from NREM sleep to wakefulness does not boost the effective connectivity between cortical columns. Instead, it is the inter-/intra-conductance ratio of cortical excitatory synapses that should raise to facilitate information propagation across the brain.

Modification of rectal function and emotion by repetitive transcranial magnetic stimulation in humans

Gut microbiota may affect function of the dorsolateral prefrontal cortex (DLPFC). However, there have been a few studies on modification of brain-gut interactions with repetitive transcranial magnetic stimulation (rTMS) to the DLPFC. We hypothesized that stimulation of the right or left DPFC by rTMS modifies the brain-gut interactions in humans. Subjects were 25 healthy males. Viscerosensory evoked potential (VEP) with sham (0 mA) or actual (30 mA) electrical stimulation (ES) of the rectum was taken after sham, low frequency rTMS at 0.1 Hz, and high frequency rTMS at 10 Hz to the right or left DLPFC. Rectal tone was measured with a rectal barostat. Visceral perception and emotion were analyzed using ordinates scale, rectal barostat, and viscerosensory evoked potential. Low frequency rTMS to the right DLPFC significantly reduced the visceral sensation and emotion composite score evoked by ES at 30 mA (p < 0.05). Plasma ACTH was significantly increased by high frequency rTMS to the right or left DLPFC (p < 0.05). Rectal fine contractions were significantly induced by low frequency rTMS to the right or left DLPFC and high frequency rTMS to the right DLPFC (p < 0.05). These results suggest that stimulation of the right or left DPFC by rTMS modifies the brain-gut interactions in humans.

Design of coils for lateralized TMS on mice

Objective. Translational studies on animals play a vital role in the advancement of transcranial magnetic stimulation (TMS) as clinical technique. Nonetheless the relevance of these procedures is frequently limited by the lack of TMS systems specifically designed for small animals capable of producing comparable stimulation conditions to those found in human TMS. In this work, we propose to take advantage of the versatility of recently introduced TMS coil design methods to produce optimal rodent-specific TMS stimulators. Approach. A stream function inverse boundary element method (IBEM) has been used for producing three small sized mice-specific TMS coils of different geometries. They have been created for unilateral hemispheric stimulation of the rodent brain, and several constraints have been considered in the design process to satisfy essential performance requirements, such as minimum stored magnetic energy, minimum power dissipation, optimised maximum current density or minimization of the undesired electric field induced in non-target regions. In order to validate the presented strategy, three prototype coils have been built. The performance of each prototype has also been numerically investigated, where the electric field induced in a mouse model has been found by using an existing computational forward technique. Main results. Stream function IBEM represents an ideally suited approach for designing specific TMS coils for small animals, capable of fulfilling many essential functional and technical requirements. The prototypes produced in this work focally stimulate the right hemisphere of the mouse brain, and so they can be successfully used in lateralized TMS experiments. Significance. The design scheme proposed here can be used to produce efficient TMS stimulators for small animals, which can overcome some of the existing limitations found when producing more reliable translational experiments.

Transcranial magnetic stimulation: a non-invasive window into the excitatory circuits involved in human motor behavior.

Transcranial magnetic stimulation (TMS) is one of the most popular non-invasive tools for investigating the cortical circuits involved in human movement. Stimulation of the primary motor cortex elicits motor evoked potentials in peripheral muscles, the amplitude of which reflects the net excitability of circuits in the cortex and spinal cord. A number of methods exist to help broadly distinguish between excitatory and inhibitory influences on corticospinal output, allowing us to probe changes in the respective cortical circuits before and during movement. Something that has rarely been considered in human TMS studies, however, is the idea that specific populations of excitatory neurons might underlie different aspects of motor behavior. The current article provides a brief review of recent TMS studies which suggest that it is possible to selectively probe distinct excitatory inputs to corticospinal neurons during a range of movement-related states, from the preparation and execution of movements, to the suppression of unwanted movements. Together with recent advancements in computational modelling of the mechanisms of TMS and the capacity to record single-cell responses to TMS in behaving non-human primates, this avenue of research has the potential to shed light on the motor circuits underlying the repertoire of human motor behaviors, as well as their pathophysiology in diseases of the motor system.

Design and Evaluation of a Rodent-Specific Transcranial Magnetic Stimulation Coil: An In Silico and In Vivo Validation Study

BackgroundRodent models are fundamental in unraveling cellular and molecular mechanisms of transcranial magnetic stimulation (TMS)‐induced effects on the brain. However, proper translation of human TMS protocols to animal models have been restricted by the lack of rodent‐specific focal TMS coils.ObjectiveWe aimed to improve TMS focalization in rodent brain with a novel small, cooled, and rodent‐specific TMS coil.MethodsA rodent‐specific 25‐mm figure‐of‐eight TMS coil was developed. Stimulation focalization was simulated in silico for the rodent coil and a commercial human 50‐mm figure‐of‐eight TMS coil. Both coils were also compared in vivo by electromyography measurements of brachialis motor evoked potential (MEP) responses to TMS at different brain sites in anesthetized rats (n = 6). Focalization was determined from the coils' level of stimulation laterality. Differences in MEPs were statistically analyzed with repeated‐measures, within‐subjects, ANOVA.Results In silico simulation results deemed the human coil insufficient for unilateral stimulation of the rat motor cortex, whereas lateralized electrical field induction was projected attainable with the rodent coil. Cortical, in vivo MEP amplitude measurements from multiple points in each hemisphere, revealed unilateral activation of the contralateral brachialis muscle, in absence of ipsilateral brachialis activation, with both coils.ConclusionComputer simulations motivated the design of a smaller rodent‐specific TMS coil, but came short in explaining the capability of a larger commercial human coil to induce unilateral MEPs in vivo. Lateralized TMS, as demonstrated for both TMS coils, corroborates their use in translational rodent studies, to elucidate mechanisms of action of therapeutic TMS protocols.

Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor μ-Alpha Rhythm.

Alpha oscillations (8–14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression for larger alpha amplitudes due to the assumed amplitude asymmetry of the oscillation. While there is evidence for this hypothesis regarding occipital alpha oscillations, it is less clear for the central sensorimotor μ-alpha rhythm. Probing corticospinal excitability via transcranial magnetic stimulation (TMS) of the primary motor cortex and the measurement of motor evoked potentials (MEPs), we have previously demonstrated that corticospinal excitability is modulated by both amplitude and phase of the sensorimotor μ-alpha rhythm. However, the direction of this modulation, its proposed asymmetry, and its underlying mechanisms remained unclear. We therefore used real-time EEG-triggered single- and paired-pulse TMS in healthy humans of both sexes to assess corticospinal excitability and GABA-A-receptor mediated short-latency intracortical inhibition (SICI) at rest during spontaneous high amplitude μ-alpha waves at different phase angles (peaks, troughs, rising and falling flanks) and compared them to periods of low amplitude (desynchronized) μ-alpha. MEP amplitude was facilitated during troughs and rising flanks, but no phasic suppression was observed at any time, nor any modulation of SICI. These results are best compatible with sensorimotor μ-alpha reflecting asymmetric pulsed facilitation but not pulsed inhibition of motor cortical excitability. The asymmetric excitability with respect to rising and falling flanks of the μ-alpha cycle further reveals that voltage differences alone cannot explain the impact of phase.SIGNIFICANCE STATEMENT The pulsed inhibition hypothesis, which assumes that alpha oscillations actively inhibit neuronal processing in a phasic manner, is highly influential and has substantially shaped our understanding of these oscillations. However, some of its basic assumptions, in particular its asymmetry and inhibitory nature, have rarely been tested directly. Here, we explicitly investigated the asymmetry of modulation and its direction for the human sensorimotor μ-alpha rhythm. We found clear evidence of pulsed facilitation, but not inhibition, in the human motor cortex, challenging the generalizability of the pulsed inhibition hypothesis and advising caution when interpreting sensorimotor μ-alpha changes in the sensorimotor system. This study also demonstrates how specific assumptions about the neurophysiological underpinnings of cortical oscillations can be experimentally tested noninvasively in humans.

Focal transcranial magnetic stimulation (TMS) of the rat brain: coil design, c-fos mapping and electrophysiology

Introduction: Rodent studies could be of great value in understanding the neurobiological mechanism of TMS. Unfortunately, there is no commercial rodent TMS coil that can mimic the spatial focality of human TMS. We report a novel system capable of inducing focal stimulation of the rat and mouse brains, with an estimate focality of about 1 mm.

The challenges of producing effective small coils for transcranial magnetic stimulation of mice

Introduction. Transcranial magnetic stimulation (TMS) is used for treating neurological disorders. Rapid pulses of magnetic field are delivered via a high-current coil situated over the scalp and induce an electric field in the brain. There has been limited fundamental scientific research on TMS and to progress it would be ideal to mimic the electric field of human TMS with mice. Animal models provide good mechanistic insight, but their use is hindered by lack of stimulating coils comparable in focus and intensity with human stimulation. Methods. We outline the engineering challenges in producing appropriate coils. It is unclear what should be optimized in the design of a mouse coil. We model the electric field, heat generation and ring-down time for cylindrical coils and use results to select a coil design consisting of 70 turns of 0.4 mm diameter copper wire wrapped around a 5 mm diameter soft ferrite core. Results and Discussion. While the magnetic flux density scales as the reciprocal of length-scale, the electric field does not scale with length, meaning that a large current is required to mimic the electric field of humans. To maximize electric field, one must minimize the coil’s inductance resulting in reduced ring-down time for the coil and significant heating. A ferrite core allows ring-down time to remain high and reduces heating. Our coil gave 180 mT at 30 V supply, with a temperature increase of 5°C after 1200 pulses at 5 Hz. The B-field below the core has a full-width-at-half-maximum of 6 mm, similar in size to a mouse brain. Conclusions. We have produced a mouse coil that offers increased B-field and reduced heating. There is considerable scope for improving electric field, but further physical analysis may lead to field strength more similar to that obtained in human TMS.

Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8-1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6-300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain.

Model-Driven Analysis of Eyeblink Classical Conditioning Reveals the Underlying Structure of Cerebellar Plasticity and Neuronal Activity.

The cerebellum plays a critical role in sensorimotor control. However, how the specific circuits and plastic mechanisms of the cerebellum are engaged in closed-loop processing is still unclear. We developed an artificial sensorimotor control system embedding a detailed spiking cerebellar microcircuit with three bidirectional plasticity sites. This proved able to reproduce a cerebellar-driven associative paradigm, the eyeblink classical conditioning (EBCC), in which a precise time relationship between an unconditioned stimulus (US) and a conditioned stimulus (CS) is established. We challenged the spiking model to fit an experimental data set from human subjects. Two subsequent sessions of EBCC acquisition and extinction were recorded and transcranial magnetic stimulation (TMS) was applied on the cerebellum to alter circuit function and plasticity. Evolutionary algorithms were used to find the near-optimal model parameters to reproduce the behaviors of subjects in the different sessions of the protocol. The main finding is that the optimized cerebellar model was able to learn to anticipate (predict) conditioned responses with accurate timing and success rate, demonstrating fast acquisition, memory stabilization, rapid extinction, and faster reacquisition as in EBCC in humans. The firing of Purkinje cells (PCs) and deep cerebellar nuclei (DCN) changed during learning under the control of synaptic plasticity, which evolved at different rates, with a faster acquisition in the cerebellar cortex than in DCN synapses. Eventually, a reduced PC activity released DCN discharge just after the CS, precisely anticipating the US and causing the eyeblink. Moreover, a specific alteration in cortical plasticity explained the EBCC changes induced by cerebellar TMS in humans. In this paper, for the first time, it is shown how closed-loop simulations, using detailed cerebellar microcircuit models, can be successfully used to fit real experimental data sets. Thus, the changes of the model parameters in the different sessions of the protocol unveil how implicit microcircuit mechanisms can generate normal and altered associative behaviors.The cerebellum plays a critical role in sensorimotor control. However, how the specific circuits and plastic mechanisms of the cerebellum are engaged in closed-loop processing is still unclear. We developed an artificial sensorimotor control system embedding a detailed spiking cerebellar microcircuit with three bidirectional plasticity sites. This proved able to reproduce a cerebellar-driven associative paradigm, the eyeblink classical conditioning (EBCC), in which a precise time relationship between an unconditioned stimulus (US) and a conditioned stimulus (CS) is established. We challenged the spiking model to fit an experimental data set from human subjects. Two subsequent sessions of EBCC acquisition and extinction were recorded and transcranial magnetic stimulation (TMS) was applied on the cerebellum to alter circuit function and plasticity. Evolutionary algorithms were used to find the near-optimal model parameters to reproduce the behaviors of subjects in the different sessions of the protocol. The main finding is that the optimized cerebellar model was able to learn to anticipate (predict) conditioned responses with accurate timing and success rate, demonstrating fast acquisition, memory stabilization, rapid extinction, and faster reacquisition as in EBCC in humans. The firing of Purkinje cells (PCs) and deep cerebellar nuclei (DCN) changed during learning under the control of synaptic plasticity, which evolved at different rates, with a faster acquisition in the cerebellar cortex than in DCN synapses. Eventually, a reduced PC activity released DCN discharge just after the CS, precisely anticipating the US and causing the eyeblink. Moreover, a specific alteration in cortical plasticity explained the EBCC changes induced by cerebellar TMS in humans. In this paper, for the first time, it is shown how closed-loop simulations, using detailed cerebellar microcircuit models, can be successfully used to fit real experimental data sets. Thus, the changes of the model parameters in the different sessions of the protocol unveil how implicit microcircuit mechanisms can generate normal and altered associative behaviors.

Approximating transcranial magnetic stimulation with electric stimulation in mouse: a simulation study.

Rodent models are valuable for preclinical examination of novel therapeutic techniques, including transcranial magnetic stimulation (TMS). However, comparison of TMS effects in rodents and humans is confounded by inaccurate scaling of the spatial extent of the induced electric field in rodents. The electric field is substantially less focal in rodent models of TMS due to the technical restrictions of making very small coils that can handle the currents required for TMS. We examine the electric field distributions generated by various electrode configurations of electric stimulation in an inhomogeneous high-resolution finite element mouse model, and show that the electric field distributions produced by human TMS can be approximated by electric stimulation in mouse. Based on these results and the limits of magnetic stimulation in mice, we argue that the most practical and accurate way to model focal TMS in mice is electric stimulation through either cortical surface electrodes or electrodes implanted halfway through the mouse cranium. This approach could allow much more accurate approximation of the human TMS electric field focality and strength than that offered by TMS in mouse, enabling, for example, focal targeting of specific cortical regions, which is common in human TMS paradigms.

Effects of periodontal afferent inputs on corticomotor excitability in humans

The aim of the present study was to determine in humans whether local anaesthesia (LA) or nociceptive stimulation of the periodontal ligaments affects the excitability of the face primary motor cortex (MI) related to the tongue and jaw muscles, as measured by transcranial magnetic stimulation (TMS). Twelve healthy volunteers (11 men, 1 woman, 25.3 +/- 4.2 years) participated in two 3-h sessions separated by 7 days. The LA carbocain or the nociceptive irritant capsaicin was randomly injected into the periodontal ligament of the lower right central incisor. In both sessions, TMS-motor evoked potential (MEP) stimulus-response curves and corticomotor maps were acquired for the tongue and masseter muscles before (baseline) and at 5, 30 and 60 min post-application of carbocain or capsaicin. Transcranial magnetic stimulation-MEP stimulus-response curves were also acquired at these time points for the first dorsal interosseous (FDI) as an internal control. Burning pain intensity and mechanical sensitivity ratings to a von Frey filament applied to the application site were recorded on an electronic visual analogue scale (VAS). All subjects reported a decreased mechanical sensitivity (anova: P = 0.004) in the LA session and a burning pain sensation (VAS peak pain: 6.4 +/- 1.0) in the capsaicin session. No significant changes in cortical excitability of the MI, as reflected by TMS-MEP stimulus-response curves or corticomotor maps for the tongue, masseter or FDI were found between baseline and post-injection for the LA (anovas: P > 0.22) or capsaicin (anovas: P > 0.16) sessions. These findings suggest that a transient loss or perturbation in periodontal afferent input to the brain from a single incisor is insufficient to cause changes in corticomotor excitability of the face MI, as measured by TMS in humans.

Lateralization of forelimb motor evoked potentials by transcranial magnetic stimulation in rats.

To approximate methods for human transcranial magnetic stimulation (TMS) in rats, we tested whether lateralized cortical stimulation resulting in selective activation of one forelimb contralateral to the site of stimulation could be achieved by TMS in the rat. Motor evoked potentials (MEP) were recorded from the brachioradialis muscle bilaterally in adult male anesthetized rats (n=13). A figure-of-eight TMS coil was positioned lateral to midline. TMS intensity was increased stepwise from subthreshold intensities to maximal machine output in order to generate input-output curves and to determine the motor threshold (MT) for brachioradialis activation. In 100% of the animals, selective activation of the contralateral brachioradialis, in the absence of ipsilateral brachioradialis activation was achieved, and the ipsilateral brachioradialis was activated only at TMS intensities exceeding contralateral forelimb MT. With increasing TMS intensity, the amplitudes of both the ipsilateral and contralateral signals increased in proportion to TMS strength. However, the input-output curves for the contralateral and ipsilateral brachioradialis were significantly different (p<0.001) such that amplitude of the ipsilateral MEP was reliably lower than the contralateral signal. We demonstrate that lateralized TMS leading to asymmetric brachioradialis activation is feasible with conventional TMS equipment in anesthetized rats. These data show that TMS can be used to assess the unilateral excitability of the forelimb descending motor pathway in the rat, and suggest that rat TMS protocols analogous to human TMS may be applied in future translational research.

Electroencephalographic recording during transcranial magnetic stimulation in humans and animals

Objective We report on the development of an EEG recording system, comprised of electrodes and amplifiers that are compatible with TMS (single and rapid-rate) in both human and animal studies. Methods We assembled a versatile multi-channel EEG recording system consisting of: (1) two types of electrodes that are safe during TMS or rTMS. (2) Low slew-rate EEG amplifiers that recover within a few milliseconds after the application of TMS pulses. Results The two electrode types: (a) a conductive-plastic surface electrode with a conductive-silver epoxy coat and (b) a subdermal silver wire electrode (SWE) are compatible to TMS pulses. The amplifiers recover within 30 ms, so that the EEG can be viewed online, essentially without interruption and/or blocking or excessive artifact. Conclusions Our TMS compatible electrode and EEG recording system allows safe and online viewing/recording of the subject's (human or animal) EEG/EP during experiments or studies involving TMS or rTMS applications. The TMS compatible electrode/amplifier system can be used with any EEG recording instrument. Significance A simple recording technique coupled with new electrodes permit safe and readable EEG records during TMS in humans and animals. Such online monitoring of the EEG would allow control of TMS/rTMS parameters based on EEG activity.

Searching for the Role of the Frontal Eye Fields in the Visual Attention Network: Figure 1.

Searching for the Role of the Frontal Eye Fields in the Visual Attention Network: Figure 1.

Cortical hemoglobin-concentration changes under the coil induced by single-pulse TMS in humans: a simultaneous recording with near-infrared spectroscopy

We measured cortical hemoglobin-concentration changes under the coil induced by single-pulse transcranial magnetic stimulation (TMS) using a technique of simultaneous recording with near-infrared spectroscopy (NIRS). Single-pulse TMS was delivered over the hand area of the left primary motor cortex at an intensity of 100, 120, or 140% of the active motor threshold (AMT). NIRS recordings were also made during sham stimulation. These four different stimulation sessions (TMS at three intensities and sham stimulation) were performed both when the subject slightly contracted the right first dorsal interosseous muscle and when relaxed it (active and resting conditions). Under the active condition with TMS at 100% AMT, we observed a transient increase in oxy-hemoglobin (oxy-Hb), which was significantly larger than sham stimulation. Under the resting conditions with TMS at 120 and 140% AMT, we observed significant decreases in both deoxy-hemoglobin (deoxyHb) and total-hemoglobin (total-Hb) as compared to sham stimulation. We suggest that the increase of oxy-Hb concentration at 100% AMT under the active condition reflects an add-on effect by TMS to the active baseline and that decrease of deoxy-Hb and total-Hb concentrations at 120 and 140% AMT under the resting condition are due to reduced baseline firings of the corticospinal tract neurons induced by a lasting inhibition provoked by a higher intensity TMS.

The sense of movement elicited by transcranial magnetic stimulation in humans is due to sensory feedback.

It has been claimed that transcranial magnetic stimulation (TMS) of the human motor cortex can produce a sense of movement of the contralateral hand, even when the hand is paralysed. The sense of movement was equated with a 'corollary discharge', a nulling mechanism originally posited for maintaining constancy of the visual field during eye movements. Our experiments were designed to test whether the sensation that accompanies TMS-evoked finger movements is generated centrally or whether it arises as a result of sensory feedback. Matched twitches of the left and right fingers were elicited either by bilateral electrical stimulation of forearm extensor muscles, or by a combination of TMS of left motor cortex (eliciting twitches of the right forefinger), and electrical stimulation of the left forearm muscles (eliciting twitches of the left forefinger). The time interval between stimuli activating left and right twitches was varied randomly (range +/- 90 ms) from trial to trial. Subjects reported whether they sensed that the left or the right movement occurred first, or if they could detect no difference. The left and right movements evoked by bilateral electrical stimulation of muscles were sensed as near simultaneous when there was zero delay between them. When TMS was applied in conjunction with unilateral muscle stimulation, the TMS-evoked movement was felt, on average, 20 ms after the movement evoked by muscle stimulation. Similar results were obtained when the skin under the cathodal electrodes was anaesthetized. Since the TMS-evoked movements were felt later rather than earlier than the electrically evoked movements, the results do not support the idea that the sensation of movement was elicited centrally by TMS. Rather, they favour sensory feedback as the source of the sense of movement. The earlier perception of electrically evoked versus TMS-evoked movements was probably due to earlier sensory responses in the periphery rather than a suppression of the excitability of somatosensory cortex.