TMS Device Research Articles

The complex landscape of TMS devices: A brief overview.

The increasing application of TMS in research and therapy has spawned an ever-growing number of commercial and non-commercial TMS devices and technology development. New CE-marked devices appear at a rate of approximately one every two years, with new FDA-approved application of TMS occurring at a similar rate. With the resulting complex landscape of TMS devices and their application, accessible information about the technological characteristics of the TMS devices, such as the type of their circuitry, their pulse characteristics, or permitted protocols would be beneficial. We here present an overview and open access database summarizing key features and applications of available commercial and non-commercial TMS devices (http://www.tmsbase.info). This may guide comparison and decision making about the use of these devices. A bibliometric analysis was performed by identifying commercial and non-commercial TMS devices from which a comprehensive database was created summarizing their publicly available characteristics, both from a technical and clinical point of view. In this document, we introduce both the commercial devices and prototypes found in the literature. The technical specifications that unify these devices are briefly analysed in two separate tables: power electronics, waveform, protocols, and coil types. In the prototype TMS systems, the proposed innovations are focused on improving the treatment regarding the patient: noise cancellation, controllable parameters, and multiple stimulation. This analysis shows that the landscape of TMS is becoming increasingly fragmented, with new devices appearing ever more frequently. The review provided here can support development of benchmarking frameworks and comparison between TMS systems, inform the choice of TMS platforms for specific research and therapeutic applications, and guide future technology development for neuromodulation devices. This standardisation strategy will allow a better end-user choice, with an impact on the TMS manufacturing industry and a homogenisation of patient samples in multi-centre clinical studies. As an open access repository, we envisage the database to grow along with the dynamic development of TMS devices and applications through community-lead curation.

Low energy magnetic stimulation of the phrenic nerve - a simulation study

Peripheral magnetic stimulation is a promising assistive technique for rehabilitation. Today’s magnetic stimulation devices, designed for transcranial stimulation, operate at currents of 6 kA and higher. This makes them expensive and bulky. Many motor neurons in peripheral nerves are more accessible, have large diameters, and require significantly lower field strengths for stimulation. In this work, we present a simulation environment to determine the threshold current required to trigger an action potential in phrenic nerve motor neurons for different coil geometries. An anatomical model was used for coil placement and realistic field calculations. The field distribution was calculated using the finite integration technique and then applied to a neuronal model to simulate the axon membrane dynamics. For general applicability, the coil-nerve distance and the axon diameter were varied. We show that the required current was approximately 1.3 kA for a nerve-coil distance of 35 mm, which corresponds to 20% of the available power of a commercial TMS device. By including the nearby vagus nerve in the simulations, we showed that accidental stimulation of this nerve is highly unlikely. Our results pave the way for the development of smaller, less complex, and more affordable stimulators and promise to increase the use of peripheral magnetic stimulators in clinical settings.

Deploying a multi-locus TMS device in a clinical environment

Deploying a multi-locus TMS device in a clinical environment

One way or another: Treatment effects of 1 Hz rTMS using different current directions in a small sample of tinnitus patients

IntroductionSo far studies on the efficacy of repetitive transcranial magnetic stimulation (rTMS) as a treatment for tinnitus are inconclusive. Two large scale placebo-controlled randomized clinical trials (RCT) examined the efficacy of low frequency temporal cortex rTMS and report different findings. As the used TMS devices differ in their used primary current direction by default, this technical parameter was speculated as a potential reason for the observed incongruences in tinnitus-related outcomes. The aim of the present pilot study was to investigate the treatment effect of 1 Hz rTMS using two different current flows. Materials and MethodsNine tinnitus patients were treated in two different groups each comprised of 10 treatment sessions á 3000 biphasic pulses of 1 Hz rTMS applied over the left temporo-parietal cortex using either an anterior-posterior to posterior-anterior (AP-PA) or posterior-anterior to anterior-posterior (PA-AP) induced current flow. Results1 Hz rTMS with a primary posterior-anterior to anterior-posterior (PA-AP) current flow caused a superior reduction in tinnitus-related symptoms, particularly tinnitus unpleasantness, loudness and tinnitus-related distress. ConclusionsThe present pilot study demonstrated that the technical TMS parameter current direction might be essential for the efficacy of rTMS as a treatment for tinnitus. Systematic investigations of technical TMS parameters like current direction in larger samples of tinnitus patients are highly needed.

TAAC - TMS Adaptable Auditory Control: A universal tool to mask TMS clicks

BackgroundCoupling transcranial magnetic stimulation with electroencephalography (TMS-EEG) allows recording the EEG response to a direct, non-invasive cortical perturbation. However, obtaining a genuine TMS-evoked EEG potential requires controlling for several confounds, among which a main source is represented by the auditory evoked potentials (AEPs) associated to the TMS discharge noise (TMS click). This contaminating factor can be in principle prevented by playing a masking noise through earphones. New methodHere we release TMS Adaptable Auditory Control (TAAC), a highly flexible, open-source, Matlab®-based interface that generates in real-time customized masking noises. TAAC creates noises starting from the stimulator-specific TMS click and tailors them to fit the individual, subject-specific click perception by mixing and manipulating the standard noises in both time and frequency domains. ResultsWe showed that TAAC allows us to provide standard as well as customized noises able to effectively and safely mask the TMS click. Comparison with existing methodsHere, we showcased two customized noises by comparing them to two standard noises previously used in the TMS literature (i.e., a white noise and a noise generated from the stimulator-specific TMS click only). For each, we quantified the Sound Pressure Level (SPL; measured by a Head and Torso Simulator - HATS) required to mask the TMS click in a population of 20 healthy subjects. Both customized noises were effective at safe (according to OSHA and NIOSH safety guidelines) and lower SPLs with respect to standard noises. ConclusionsAt odds with previous methods, TAAC allows creating effective and safe masking noises specifically tailored on each TMS device and subject. The combination of TAAC with tools for the real-time visualization of TEPs can help control the influence of auditory confounds also in non-compliant patients. Finally, TAAC is a highly flexible and open-source tool, so it can be further extended to meet different experimental requirements.

Programmable Transcranial Magnetic Stimulation: A Modulation Approach for the Generation of Controllable Magnetic Stimuli.

A transcranial magnetic stimulation system with programmable stimulus pulses and patterns is presented. The stimulus pulses of the implemented system expand beyond conventional damped cosine or near-rectangular pulses and approach an arbitrary waveform. The desired stimulus waveform shape is defined as a reference signal. This signal controls the semiconductor switches of an H-bridge inverter to generate a high-power imitation of the reference. The design uses a new paradigm for TMS, applying pulse-width modulation with a non-resonant, high-frequency switching architecture to synthesize waveforms that leverages the low-pass filtering properties of neuronal cells. The modulation technique enables control of the waveform, frequency, pattern, and intensity of the stimulus. A system prototype was developed to demonstrate the technique. The experimental measurements demonstrate that the system is capable of generating stimuli up to 4 kHz with peak voltage and current values of ±1000 V and ±3600 A, respectively. The maximum transferred energy measured in the experimental validation was 100.4 Joules. To characterize repetitive TMS modalities, the efficiency of generating consecutive pulse triplets and quadruplets with interstimulus intervals of 1 ms was tested and verified. The implemented TMS device can generate consecutive rectangular pulses with a predetermined time interval, widths and polarities, enables the synthesis of a wide range of magnetic stimuli. New waveforms promise functional advantages over the waveforms generated by current-generation TMS systems for clinical neuroscience research.

The therapeutic effect of repetitive transcranial magnetic stimulation in elderly depression patients.

Background:Depression, a common psychiatric disorder in elderly, serves as a remarkable precipitating factor for suicide among the elderly people. Here, a randomized double-blinded study was performed to investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) on improving the clinical symptoms and reducing suicidal ideation in elderly patients with depression.Methods:In this study, 103 elderly patients with depression and suicidal ideation were randomly divided into 2 groups, 48 cases in the rTMS group and 55 cases in the control group (sham rTMS). Both groups received routine drug therapy with rTMS or sham rTMS. The patients received evaluation by Hamilton depression scale and self-rating idea of suicide scale before treatment and after 2 and 4 weeks of treatment, respectively.Results:The measurement from the present study demonstrated that Hamilton depression scale and self-rating idea of suicide scale scores decreased to varying degrees in the 2 groups after treatment, and the decrease was more significant in rTMS group. The rate of marked effectiveness was much higher in rTMS group after 2 weeks of treatment compared with the control group. Furthermore, the rate of moderate effectiveness at 4 weeks after treatment was significantly higher in rTMS group compared with the control group.Conclusion:Together, the present study shows that rTMS with routine drug therapy exhibited effect with quick onset to improve the clinical symptoms and reduce suicidal ideation in elderly patients with depression.

Solving an IBEM with supporting vector analysis to design quiet TMS coils

Transcranial magnetic stimulation is a promising tool in neuroscience of which successful development is affected by the loud click noise originated when the stimulating coil is energized. This undesired sound is produced by the coil winding deformations generated by the Lorentz self-forces in the TMS device. Addressing the need for TMS systems that produce less noise, a quiet coil design technique is proposed in this work, where instead of minimizing directly the coil deflection, the Lorentz self-force is optimized in order to reduce the acoustic noise. The presented method is based on a stream function IBEM for TMS coil design in which new computational models have been incorporated into the optimization problem, which is efficiently solved by using supporting vector analysis. Several examples of coils of different geometries were designed and simulated to demonstrate the efficiency of the suggested IBEM approach to produce TMS devices that experience minimum Lorentz self-forces. In order to evaluate the acoustic response of the designed TMS coils, the commercial MSC/NASTRAN was used to find the coil deflection. The obtained results show that significant noise reduction can be achieved by minimizing the Lorentz self-force over the TMS coil surface.

Method to assess the mismatch between the measured and nominal parameters of transcranial magnetic stimulation devices

BackgroundSmall variations in TMS parameters, such as pulse frequency and amplitude may elicit distinct neurophysiological responses. Assessing the mismatch between nominal and experimental parameters of TMS stimulators is essential for safe application and comparisons of results across studies. New methodA search coil was used to assess exactness and precision errors of amplitude and timing parameters such as interstimulus interval, the period of pulse repetition, and intertrain interval of TMS devices. The method was validated using simulated pulses and applied to six commercial stimulators in single-pulse (spTMS), paired-pulse (ppTMS), and repetitive (rTMS) protocols, working at several combinations of intensities and frequencies. ResultsIn a simulated signal, the maximum exactness error was 1.7% for spTMS and the maximum precision error 1.9% for ppTMS. Three out of six TMS commercial devices showed exactness and precision errors in spTMS amplitude higher than 5%. Moreover, two devices showed amplitude exactness errors higher than 5% in rTMS with parameters suggested by the manufactures. Comparison with existing methodsCurrently available tools allow characterization of induced electric field intensity and focality, and pulse waveforms of a single TMS pulse. Our method assesses the mismatch between nominal and experimental values in spTMS, ppTMS and rTMS protocols through the exactness and precision errors of amplitude and timing parameters. ConclusionThis study highlights the importance of evaluating the physical characteristics of TMS devices and protocols, and provides a method for on-site quality assessment of multiple stimulation protocols in clinical and research environments.

Neurocognitive Effects of Repetitive Transcranial Magnetic Stimulation With a 2-Coil Device in Treatment-Resistant Major Depressive Disorder.

Neurocognitive dysfunction is an understudied and undertreated aspect of psychiatric research and treatment. There is emerging evidence to suggest that repetitive transcranial magnetic stimulation (rTMS) may possess neurocognition-enhancing capabilities. This study examined the neurocognitive data from a randomized, double-blind, sham-controlled trial of an investigational 2-coil rTMS device in antidepressant treatment or treatment-intolerant major depressive disorder patients. This device has the potential to stimulate deeper areas of the brain than the Food and Drug Administration-approved TMS devices, which primarily stimulate cortical brain areas and may therefore have different neurocognitive adverse effects. Patients received 20 daily rTMS treatments (10-Hz stimulation; either active or sham) with coil centers positioned over the left dorsolateral prefrontal cortex and dorsomedial prefrontal cortex. Neurocognitive safety was evaluated at baseline and within 72 hours of final treatment session with a computerized battery assessing aspects of attention and memory in 84 participants. There were no observed negative neurocognitive effects of the 2-coil rTMS device. A significant effect of active rTMS was observed on the quality of episodic memory. There were no observed effects for attention or working memory. Baseline quality of episodic memory predicted depression treatment response and remission, in that lower baseline episodic memory was associated with greater likelihood of depression response/remission. This was observed in logistic regression analyses controlling for treatment and baseline depressive symptoms. The 2-coil rTMS device is a cognitively safe treatment for treatment-resistant depression that may possess episodic memory-enhancing capabilities. Furthermore, baseline episodic memory may reflect an important predictor of subsequent depression treatment response/remission to rTMS.

P159 Specific and non-specific inhibition of interneurons circuits during motor preparation and suppression

Introduction Corticospinal excitability is transiently suppressed during motor preparation (Greenhouse et al., 2015 ) and when cancelling a prepared movement (Hoshiyama et al., 1997 ). Because MEPs are suppressed even in task-irrelevant muscles Greenhouse et al., 2015 , Hoshiyama et al., 1997 ), it has been proposed that there is a “global” inhibitory signal (Greenhouse et al., 2015) . Objectives We tested the whether the inhibition is global or specific to different excitatory interneuron circuits in primary motor cortex (M1). Materials & methods A controllable pulse parameter TMS (cTMS; Rogue Resolutions Ltd.) device was used to activate distinct interneuron circuits in M1 by changing the coil orientation (posterior–anterior, PA; anterior–posterior, AP) and TMS pulse width (30–120 μs). Motor evoked potentials (MEPs) were elicited in the first dorsal interosseous muscle(s) using short AP- (AP30) and long PA-directed (PA120) pulses at various stages during: (1) a left/right choice reaction time task (CRTT) in which a non-informative warning cue appeared 0.5 s prior to the imperative signal indicated the required response; and (2) a Go/No-Go task in which a non-informative warning cue appeared 2 s prior to a Go or No-Go signal indicating to respond or not respond. Because TMS pulse specificity is greatest at low stimulus intensities, experiments were conducted with weak voluntary contraction (5–10% maximum) to reduce stimulus threshold. Results AP30 pulses evoked MEPs with a longer latency than PA120 pulses, confirming that different excitatory interneurons were recruited by the different pulse. [RH1] In the CRTT, the amplitude of AP30-evoked MEPs was suppressed at the time of the imperative stimulus in both responding and non-responding hands, whereas responses to PA120 stimuli were unaffected (Fig. 1A) Download : Download high-res image (366KB) Download : Download full-size image .[RH2] In the Go/No-Go task, AP30 and PA120 MEPs were suppressed to a similar extent in the No-Go condition near to the expected onset of movement (Fig. 1B). Conclusion During motor preparation for the CRTT there was a selective suppression of one interneuron circuit in M1. In contrast, a global inhibition of corticospinal excitability was observed following a decision not to move. The implication is that the mechanisms underlying each form of inhibition are at least partially distinct.

Pulse Duration as Well as Current Direction Determines the Specificity of Transcranial Magnetic Stimulation of Motor Cortex during Contraction.

Previous research suggested that anterior-posterior (AP) directed currents induced by TMS in motor cortex (M1) activate interneuron circuits different from those activated by posterior-anterior currents (PA). The present experiments provide evidence that pulse duration also determines the activation of specific interneuron circuits. To use single motor unit (SMU) recordings to confirm the difference in onset latencies of motor-evoked potentials (MEPs) evoked by different current directions and pulse durations: AP30, AP120, PA30 and PA120. To test whether the amplitude of the MEPs is differentially influenced by somatosensory inputs from the hand (short-latency afferent inhibition, SAI), and examine the sensitivity of SAI to changes in cerebellar excitability produced by direct current stimulation (tDCSCb). Surface electromyograms and SMUs were recorded from the first dorsal interosseous muscle. SAI was tested with an electrical stimulus to median or digital nerves ~20-25 ms prior to TMS delivered over the M1 hand area via a controllable pulse parameter TMS (cTMS) device. SAI was also tested during the application of anodal or sham tDCSCb. Because TMS pulse specificity is greatest at low stimulus intensities, most experiments were conducted with weak voluntary contraction to reduce stimulus threshold. AP30 currents recruited the longest latency SMU and surface MEP responses. During contraction SAI was greater for AP30 responses versus all other pulses. Online anodal tDCSCb reduced SAI for the AP30 currents only. AP30 currents activate an interneuron circuit with functional properties different from those activated by other pulse types. Pulse duration and current direction determine what is activated in M1 with TMS.

Clinical Outcomes of TMS treatment

Shinjuku Mental Clinic (SMC) is a TMS treatment center equipped with 83 NeuroStars (54 in Tokyo, 20 in Osaka and 9 in Nagoya), a TMS device. Since opening of the clinic in June, 2013, 481 patients (as of December, 2014) have undergone treatment for major depressive disorder (MDD) and bipolar disorder.

Adding Low-Field Magnetic Stimulation to Noninvasive Electromagnetic Neuromodulatory Therapies

Adding Low-Field Magnetic Stimulation to Noninvasive Electromagnetic Neuromodulatory Therapies

Präfrontale Kontrolle von Erwartungen bei der Placebo-Analgesie

Expectations and beliefs modulate the experience of pain, which is particularly evident in placebo analgesia. The dorsolateral prefrontal cortex (DLPFC) has been associated with pain regulation and with the generation, maintenance and manipulation of cognitive representations. In a heat-pain paradigm, we employed non-invasive low-frequency repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt left and right DLPFC function or used the TMS device itself as a placebo, before applying an expectation-induced placebo analgesia. The results demonstrated that placebo significantly increased pain threshold and pain tolerance. While rTMS did not affect pain experience, it completely blocked placebo analgesia. These findings suggest that expectation-induced placebo analgesia is mediated by symmetric prefrontal cortex function. Possible implications for medical practice and clinical trial research will be discussed in the article.

Prefrontal cortex modulates placebo analgesia

Expectations and beliefs modulate the experience of pain, which is particularly evident in placebo analgesia. The dorsolateral prefrontal cortex (DLPFC) has been associated with pain regulation and with the generation, maintenance and manipulation of cognitive representations, consistent with its role in expectation. In a heat-pain paradigm, we employed non-invasive low-frequency repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt left and right DLPFC function or used the TMS device itself as a placebo, before applying an expectation-induced placebo analgesia. The results demonstrated that placebo significantly increased pain threshold and pain tolerance. While rTMS did not affect pain experience, it completely blocked placebo analgesia. These findings suggest that expectation-induced placebo analgesia is mediated by symmetric prefrontal cortex function.

Treatment Key to Reducing Cost of Crime

Somatic treatments benefit some people whose depression persists after treatment with medication, psychotherapy, and a combination of these two, said Mark George, MD, professor of psychiatry and director of the brain stimulation laboratory at the Medical University of South Carolina, in Charleston. Refinements of electroconvulsive therapy that use a shorter pulse width yield efficacy comparable with older techniques, with less cognitive dysfunction, George said. In 2005, the US Food and Drug Administration approved vagus nerve stimulation for treatment-resistant depression. This technique requires implantation of a pacemaker in the neck to stimulate the left vagus nerve. Repetitive transcranial magnetic stimulation (rTMS) has generated the most excitement among researchers in therapeutic neuromodulation, George said, as rTMS is non-invasive, and, in studies to date, has not been shown to have deleterious cognitive effects. This still-investigative technique involves external application of magnetic fields that stimulate the cortex. A 20-site study of 301 patients with difficult-to-treat depression who received either rTMS or sham rTMS as outpatients for 35 min/d, 5 d/wk, for up to 6 weeks, followed by a 3-week taper phase, found greater improvement on standard depression rating scales in the active treatment group than in the sham treatment group, according to a report at another symposium at the Toronto meeting. John O’Reardon, MD, assistant professor of psychiatry at the University of Pennsylvania School of Medicine, Philadelphia, principal investigator at that site, described findings from this study, funded by Neuronetics Inc, a TMS device manufacturer. A replication trial sponsored by the National Institutes of Health is now in progress.