Mechanisms Of Transcranial Magnetic Stimulation Research Articles

Non-invasive TMS attenuates neuropathic pain after spinal cord injury associated with enhancing brain functional connectivity and HPA axis activity

Patients with spinal cord injury (SCI) often suffer from varying degrees of neuropathic pain.Non-invasive repetitive transcranial magnetic stimulation (TMS) has been shown to improve neuropathic pain, while the appropriate intervention strategies of TMS treatment and how TMS affects brain function after SCI were not entirely clear. To investigate the effects and mechanisms of TMS on neuropathic pain after SCI, high-frequency TMS on primary motor cortex (M1) of mice was performed after SCI and pain response was evaluated through an electronic Von-Frey device and cold/hot plates. Functional magnetic resonance imaging (fMRI), bulk RNA sequencing, immunofluorescence and molecular experiments were used to evaluate brain and spinal cord function changes and mechanisms. TMS significantly improved SCI induced mechanical allodynia, cold and thermal hyperalgesia with a durative effect, and TMS intervention at 1 week after SCI had pain relief advantages than at 2 weeks. TMS intervention not only affected the functional connections between the primary motor cortex and the thalamus, but also increased the close connection of multiple brain regions. Importantly, TMS treatment activated the hypothalamic pituitary adrenal (HPA) axis and increased the transcript levels of genes encode hormone proteins, accompanied with the attenuation of inflammatory microenvironment in spinal cord associated with pain relief. Totally, these results elucidate that early intervention with TMS could improve neuropathic pain after SCI associated with enhancing brain functional connectivity and HPA axis activity which should be harnessed to modulate neuropathic pain after SCI.

TMS and neocortical neurons: an integrative review on the micro-macro connection in neuroplasticity.

Tian D, Izumi S. TMS and neocortical neurons: an integrative review on the micro-macro connection in neuroplasticity. Jpn J Compr Rehabil Sci 2023; 14: 1-9. Neuroplasticity plays a pivotal role in neuroscience and neurorehabilitation as it bridges the organization and reorganization properties of the brain. Among the numerous neuroplastic protocols, transcranial magnetic stimulation (TMS) is a well-established non-invasive protocol to induce plastic changes in the brain. Here, we review the findings of four plasticity-inducing TMS protocols in the human motor cortex with relatively evident mechanisms: conventional repetitive TMS (rTMS), theta-burst stimulation (TBS), quadripulse stimulation (QPS) and paired associative stimulation (PAS). Based on the reviewed evidence and a preliminary TMS neurocytological model proposed in our previous report, we further integrate the neurophysiological evidence and plasticity rules of these protocols to present an updated micro-macro connection model between neocortical neurons and the neurophysiological evidence in TMS. This prototypical model will guide further efforts to understand the neural circuit of the motor cortex, the mechanisms of TMS, and the advance of neuroplasticity technologies and their outcomes.

Cellular mechanisms of transcranial magnetic stimulation in an in vitro turtle cerebellum

Cellular mechanisms of transcranial magnetic stimulation in an in vitro turtle cerebellum

Neuromodulatory effects of repetitive transcranial magnetic stimulation on neural plasticity and motor functions in rats with an incomplete spinal cord injury: A preliminary study.

We investigated the effects of intermittent theta-burst stimulation (iTBS) on locomotor function, motor plasticity, and axonal regeneration in an animal model of incomplete spinal cord injury (SCI). Aneurysm clips with different compression forces were applied extradurally around the spinal cord at T10. Motor plasticity was evaluated by examining the motor evoked potentials (MEPs). Long-term iTBS treatment was given at the post-SCI 5th week and continued for 2 weeks (5 consecutive days/week). Time-course changes in locomotor function and the axonal regeneration level were measured by the Basso Beattie Bresnahan (BBB) scale, and growth-associated protein (GAP)-43 expression was detected in brain and spinal cord tissues. iTBS-induced potentiation was reduced at post-1-week SCI lesion and had recovered by 4 weeks post-SCI lesion, except in the severe group. Multiple sessions of iTBS treatment enhanced the motor plasticity in all SCI rats. The locomotor function revealed no significant changes between pre- and post-iTBS treatment in SCI rats. The GAP-43 expression level in the spinal cord increased following 2 weeks of iTBS treatment compared to the sham-treatment group. This preclinical model may provide a translational platform to further investigate therapeutic mechanisms of transcranial magnetic stimulation and enhance the possibility of the potential use of TMS with the iTBS scheme for treating SCIs.

Mechanisms of transcranial magnetic stimulation in the treatment of anorexia nervosa

AimsSevere and Enduring Anorexia Nervosa (SE-AN) is a challenging condition to treat, with limited therapeutic options, high morbidity, and the highest mortality rates of any psychiatric illness. Repetitive Transcranial Magnetic Stimulation (rTMS) is an emerging treatment option, as evidence demonstrates promising efficacy in improving mood and reducing core Anorexia Nervosa symptoms, as well as safety and tolerability to patients. We aimed to investigate the neurophysiological mechanisms of rTMS use in SE-AN patients by assessing changes in resting state functional connectivity, in the first functional neuroimaging analysis investigating rTMS effects in Anorexia Nervosa patients.Method26 females with a current diagnosis of SE-AN received 20 sessions of sham or real high frequency rTMS (10 hertz) to the left dorsolateral prefrontal cortex in a randomised double-blind trial. Resting-state functional magnetic resonance imaging was performed before and after rTMS. Neural correlates of rTMS treatment were identified using a seed-based functional connectivity analysis with the left dorsolateral prefrontal cortex and bilateral amygdalae as regions of interest. Functional connectivity differences were analysed using t-contrasts in a mixed ANOVA (flexible factorial analysis) to assess interactions between treatment group (real rTMS vs sham) and time-point (pre or post TMS).ResultNo statistically significant changes in resting-state functional connectivity were observed post-rTMS compared to baseline in participants receiving active rTMS compared to sham. Increased functional connectivity between the left amygdala and left pre-supplementary motor area was observed to reach cluster-wise significance (PFWE < 0.05). However, after Bonferroni correction for multiple comparisons (3 seed regions), this did not reach the significance threshold PFWE <0.017.ConclusionThis study highlights the need for further investigation of neurophysiological mechanisms, including resting-state functional connectivity modulation, resulting from rTMS to the dorsolateral prefrontal cortex in SE-AN patients. This requires higher powered studies to account for heterogeneity in treatment response. We have provided some indication that high frequency rTMS may have therapeutic benefit in SE-AN by modification of functional connectivity between prefrontal and limbic brain regions, resulting in improved top-down cognitive control over emotional processing and ability to enact goal-directed behaviours, enabling secondary reductions in eating disorder behaviours.

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.

Neurobiological mechanisms of transcranial magnetic stimulation and its comparative efficacy in tension headache and migraine

Transcranial magnetic stimulation (TMS) is one of the nonpharmacological methods to affect the central nervous system. This approach allows a noninvasive stimulation of the cerebral cortex. The method is based on the ability of magnetic fields to penetrate the bone and muscle structures. The induced magnetic field depolarizes the neuronal membrane, and the generated action potential propagates through the conducting pathways. In the review, the biophysical effects of TMS, as well as its neural, immune, mediator and macro effects are analyzed. The main contraindications to TMS and its side effects are considered. Nonpharmacological treatment of tension headache (TH) and migraine is a promising direction, since the incidence of these types of primary headaches reaches 40-65 and 11-22%, respectively. In the article the current state of study of various modes and durations of TMS procedure, and the site of exposure in TH and migraine are considered. In recent years there is noted an increase in the number of evidence-based randomized, placebo-controlled studies on the effectiveness of TMS in migraine therapy. Much attention is given to evaluation of the effect of TMS in migraine. There is much evidence of the positive effect of this procedure. However, the amount of examined volunteers does not provide the highest level of evidence. Experiments on animals and use of functional neurovisualization techniques contribute to understanding of the mechanisms of TMS effect. Active participation of physiologists, neurophysiologists and biophysicists in these research works will permit evaluation of the effectiveness of TMS in nonpharmacological treatment of patients with pain syndrome. This approach will improve the working capacity and quality of life in TH and migraine.

Neurobiological mechanisms of transcranial magnetic stimulation and its comparative efficacy in tension headache and migraine

Transcranial magnetic stimulation (TMS) is one of the nonpharmacological methods to affect the central nervous system. This approach allows a noninvasive stimulation of the cerebral cortex. The method is based on the ability of magnetic fields to penetrate the bone and muscle structures. The induced magnetic field depolarizes the neuronal membrane, and the generated action potential propagates through the conducting pathways. In the review, the biophysical effects of TMS, as well as its neural, immune, mediator and macro effects are analyzed. The main contraindications to TMS and its side effects are considered. Nonpharmacological treatment of tension headache (TH) and migraine is a promising direction, since the incidence of these types of primary headaches reaches 40-65 and 11-22%, respectively. In the article the current state of study of various modes and durations of TMS procedure, and the site of exposure in TH and migraine are considered. In recent years there is noted an increase in the number of evidence-based randomized, placebo-controlled studies on the effectiveness of TMS in migraine therapy. Much attention is given to evaluation of the effect of TMS in migraine. There is much evidence of the positive effect of this procedure. However, the amount of examined volunteers does not provide the highest level of evidence. Experiments on animals and use of functional neurovisualization techniques contribute to understanding of the mechanisms of TMS effect. Active participation of physiologists, neurophysiologists and biophysicists in these research works will permit evaluation of the effectiveness of TMS in nonpharmacological treatment of patients with pain syndrome. This approach will improve the working capacity and quality of life in TH and migraine.

Mechanisms of Transcranial Magnetic Stimulation Treating on Post-stroke Depression.

Post-stroke depression (PSD) is a neuropsychiatric affective disorder that can develop after stroke. Patients with PSD show poorer functional and recovery outcomes than patients with stroke who do not suffer from depression. The risk of suicide is also higher in patients with PSD. PSD appears to be associated with complex pathophysiological mechanisms involving both psychological and psychiatric problems that are associated with functional deficits and neurochemical changes secondary to brain damage. Transcranial magnetic stimulation (TMS) is a non-invasive way to investigate cortical excitability via magnetic stimulation of the brain. TMS is currently a valuable tool that can help us understand the pathophysiology of PSD. Although repetitive TMS (rTMS) is an effective treatment for patients with PSD, its mechanism of action remains unknown. Here, we review the known mechanisms underlying rTMS as a tool for better understanding PSD pathophysiology. It should be helpful when considering using rTMS as a therapeutic strategy for PSD.

On the Mechanisms of Transcranial Magnetic Stimulation (TMS): How Brain State and Baseline Performance Level Determine Behavioral Effects of TMS.

The behavioral effects of Transcranial Magnetic Stimulation (TMS) can change qualitatively when stimulation is preceded by initial state manipulations such as priming or adaptation. In addition, baseline performance level of the participant has been shown to play a role in modulating the impact of TMS. Here we examined the link between these two factors. This was done using data from a previous study using a TMS-priming paradigm, in which, at group level, TMS selectively facilitated targets incongruent with the prime while having no statistically significant effects on other prime-target congruencies. Correlation and linear mixed-effects analyses indicated that, for all prime-target congruencies, a significant linear relationship between baseline performance and the magnitude of the induced TMS effect was present: low levels of baseline performance were associated with TMS-induced facilitations and high baseline performance with impairments. Thus as performance level increased, TMS effects turned from facilitation to impairment. The key finding was that priming shifted the transition from facilitatory to disruptive effects for targets incongruent with the prime, such that TMS-induced facilitations were obtained until a higher level of performance than for other prime-target congruencies. Given that brain state manipulations such as priming operate via modulations of neural excitability, this result is consistent with the view that neural excitability, coupled with non-linear neural effects, underlie behavioral effects of TMS.

SP-2. What dose TMS stimulate?

Transcranial magnetic stimulation (TMS) is a technique to stimulate the nervous system non-invasively through the intact scalp and skin. The TMS machine delivers a short pulse of electric current into a TMS coil to generate a quick changing magnetic field surrounding the coil as an example of Ampere’s law. TMS stimulates the neuronal circuits with the eddy current induced by the changing magnetic field, not the magnetic field its self, based on Faraday’s law. To generate enough power for stimulating human’s brain, a TMS machine is generally built to generate a current of around 8000 A for a 2.5–4 Tesla output, although it may vary between machine types and manufacturers. TMS is capable of stimulating human’s cortex to induce recordable responses, e.g. motor evoked potentials (MEPs). However, how TMS actives the circuits and what TMS stimulates is in fact more complicated than most people think. The current knowledge of what TMS stimulates is mainly learned from the stimulation over the motor cortex generating MEPs. In this session, the mechanism of TMS will be explained, the effects of TMS over the motor cortex will be introduced and the underlying mechanisms of how TMS induces such responses and effects will be discussed.

Defining Mechanisms of Transcranial Magnetic Stimulation as a Treatment for Depression Through Neuroimaging: Progress and Challenges

Defining Mechanisms of Transcranial Magnetic Stimulation as a Treatment for Depression Through Neuroimaging: Progress and Challenges

Effect of Transcranial Magnetic Stimulation of Acupuncture Point on Brain Network

Transcranial magnetic stimulation (TMS), as a new therapy, has been proven to be efficient in inducing electric fields in the neuronal tissues and modulating brain activity in the applications to stimulate different positions of human body such as the brain, peripheral nerves, and acupuncture points (acupoint) in the last decade. Acupuncture, an ancient therapeutic technique, is gaining popularity in Western medicine, but the underlying regulation mechanism of acupuncture has not been well understood and still needs to be further investigated. By using electroencephalogram, signals before and following stimulation of Shenmen acupoint (HT7) were acquired noninvasively. Then, we adopted a network model analysis from graph theory to construct a network and evaluate network measures of brain connectivity among multiple brain regions before and following stimulation. An analysis of the resulting brain functional network found that the parietal lobe and parietal-occipital lobe shared lower degree and strength following stimulation than before and the frontal lobe shared higher betweenness centrality than before. The network measures with significant differences were distributed over the brain areas contralateral to the stimulated hand, which has probable association with the regulation mechanism of TMS of HT7 acupoint.

P090 Excitation mechanisms of TMS on cortical neuron models

Introduction Transcranial Magnetic Stimulation (TMS) is a non-invasive method for neuromodulation, with a range of clinical and research applications including the treatment of depression and functional brain mapping. TMS works by generating a time-varying magnetic field which induces an electric field (E-field) in the brain. Despite its widespread use, understanding of the neural effects of TMS is limited, making it difficult to address issues like high subject-to-subject variability and optimization of stimulation protocols. Computational modeling offers the opportunity to unravel the mechanisms of TMS in ways that are infeasible experimentally. Objectives We used cortical neuron models to investigate which neural elements are activated by TMS and how the threshold for action potential (AP) initiation varies with field orientation. Materials & methods We adapted models from the experimentally validated library of rat cortical neurons developed by the Blue Brain Project. These are multi-compartment, conductance-based cable models with realistic 3D morphologies implemented in the NEURON modeling software. The models were coupled to extracellular potentials calculated in MATLAB. Since the neural processes in the cortex are short relative to the E-field spatial gradient, the E-field was approximated as uniform. Threshold “maps” for activation were determined using a binary search algorithm at field orientations sweeping the polar and azimuthal directions. Results The site of action potential (AP) initiation and maximum depolarization was nearly always an axonal termination parallel to the field, with the exception of some orientations maximally depolarizing bifurcations near pre-synaptic terminals. Due to the high degree of branching and spatial extent of the realistic axons included in these models, the threshold maps indicated relative insensitivity to orientation and exhibited numerous local minima of thresholds, dependent on the specific axon morphology. Conclusion Within the assumptions of these models, axon terminals are typically the lowest threshold elements of cortical neurons for E-fields with low spatial gradients, and morphological differences between cell-types directly affect threshold values.

T029 Where do we stimulate M1? A combined neurophysiological and modelling approach

Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. Very surprisingly, however, it is still unclear which part of M1 is stimulated by TMS when a muscle twitch is elicited. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. I will report on two recent studies which combined electrophysiological measurements of muscle responses to TMS with realistic estimates of the induced electric field, based on the finite-element method (FEM) and MRI-derived individual head models. In the first study, the orientation of a standard figure 8 coil was systematically varied and the field changes in different subparts of the motor cortex were compared with the electrophysiological threshold changes. In the second study, three figure 8 coils having different field decays were used and the differences in the electrophysiological thresholds were correlated with the differences in the calculated field distributions. Both studies consistently demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our studies are one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for two hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.

Where does TMS Stimulate the Motor Cortex? Combining Electrophysiological Measurements and Realistic Field Estimates to Reveal the Affected Cortex Position.

Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our study is one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for 2 hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.

The effect of swallowing treatments on corticobulbar excitability: a review of transcranial magnetic stimulation induced motor evoked potentials.

Transcranial magnetic stimulation (TMS) has been used extensively as a method of investigating the corticomotor physiology of many motor tasks, including healthy and disordered swallowing. Changes in excitability of cortical projections to various swallowing muscles have been documented in response to treatments with TMS induced motor evoked potentials (MEPs). These studies have provided valuable insight into CNS response to swallowing impairment, and more importantly, the adaptations associated with functional recovery. However, unique obstacles are presented when investigating corticobulbar neurophysiology associated with the complex task of swallowing. Stringent methodological control and supplementary outcome measures are required to ensure robust and clinically applicable findings. This article offers a tutorial for the researcher who may be considering the use of TMS for investigating changes in cortical excitability associated with various swallowing paradigms. Included is a review of the mechanisms of TMS and what can be measured with this technique, a summary of existing research using MEPs to investigate swallowing, a review of methodological factors that may influence outcomes, and proposed directions for new areas of research.

The Science of Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a noninvasive method for stimulating neural tissue based on the principles of electromagnetic induction. The technique is becoming an established treatment for drug-resistant major depressive disorder and is a promising tool for a variety of psychiatric and neurological disorders. Stimulation is achieved by pulsed magnetic fields inducing electric fields with the necessary characteristics to depolarize neurons, generating action potentials. In this article, the underlying principles and mechanisms of TMS are explored and an overview of the development of stimulator devices is provided. [ Psychiatr Ann . 2014; 44(6):279–283.]

Probing the involvement of the right hemisphere in language processing with online transcranial magnetic stimulation in healthy volunteers

Background: Current models emphasize that language-related functions are predominantly organized in left-lateralized fronto-temporo-parietal cortical networks. Aims: In this review, we summarize how “online” transcranial magnetic stimulation (TMS) during a language task can be used in healthy individuals to characterize the contribution of the stimulated area to a specific language function with a focus on the functional relevance of the right hemisphere. We first give an introduction to some basic mechanisms of TMS and outline the prerequisites for carrying out TMS studies of language. In particular, we highlight some methodological limitations and pitfalls of the TMS approach. We then review online TMS studies of language processing with a particular focus on the contribution of right hemisphere brain regions to language processing. Main Contribution: The majority of TMS studies on language have targeted a single left- hemisphere cortical area during a language task to identify the relevance of that area for a specific aspect of language processing. TMS has also been used to characterize the involvement of homologous right hemisphere regions. These studies have provided evidence for a significant role of right hemisphere regions in different aspects of language processing, including word comprehension, reading and paralinguistic features like emotional prosody. Conclusions: Recently, two areas have been targeted simultaneously with TMS while subjects performed a language task. This multifocal TMS approach has opened up new possibilities to compare the functional involvement of homologous regions in the right and left hemisphere and allows for the characterization of interhemispheric compensation during language processing.

Intrinsic Functional Connectivity with the Subgenual Cingulate Predicts Clinical Efficacy of TMS Targets for Depression (P01.188)

Objective: To elucidate the antidepressant mechanism of transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) and translate this information into improved TMS targeting and clinical efficacy. Background TMS to the left DLPFC is used clinically for the treatment of depression. However the antidepressant mechanism remains unclear and its therapeutic efficacy remains limited. One problem known to contribute to limited clinical efficacy is difficulty identifying the appropriate stimulation target. Recent data suggests that some left DLPFC targets are more effective than others; however the reasons for this heterogeneity and how to capitalize on this information remain unclear. Design/Methods: Intrinsic (resting state) functional connectivity MRI was used to determine if differences in functional connectivity could account for differences in clinical efficacy across various left DLPFC TMS sites. We then utilized this information to compute ideal stimulation coordinates using connectivity-based targeting. Results: The clinical efficacy of different DLPFC stimulation sites was related to the strength of their anticorrelation with the subgenual cingulate, both through paired comparisons and on a continuous basis. Optimal left DLPFC coordinates were identified based on subgenual connectivity to be targeted in future TMS clinical trials. Conclusions: This work lends insight into the antidepressant mechanism of TMS and the role of intrinsically anticorrelated networks in depression. Further, it suggests a targeting strategy to optimize focal brain stimulation that could have broad applicability across a number of diseases and stimulation techniques. Supported by: The Brain Genomics Superstruct Project, NIH Grant R25NS065743, National Institutes of Health and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758) and the Howard Hughes Medical Institute. Disclosure: Dr. Fox has nothing to disclose. Dr. Pascual-Leone has received personal compensation for activities with Nexstim, Neuronix, Starlab Neuroscience, Allied Mind, Neosync, and Novavision.