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Abstract

Transcranial magnetic stimulation (TMS) is widely used for noninvasive activation of neurons in the brain for research and clinical applications. The strong, brief magnetic pulse generated in TMS is associated with a loud (>100 dB) clicking sound that can impair hearing and that activates auditory circuits in the brain. We introduce a two-pronged solution to reduce TMS noise by redesigning both the pulse waveform and the coil structure. First, the coil current pulse duration is reduced which shifts a substantial portion of the pulse acoustic spectrum above audible frequencies. Second, the mechanical structure of the stimulation coil is designed to suppress the emergence of the sound at the source, diminish down-mixing of high-frequency sound into the audible range, and impede the transmission of residual sound to the coil surface but dissipate it away from the casing. A prototype coil driven with ultrabrief current pulses (down to 45-μs biphasic duration) is demonstrated to reduce the peak sound pressure level by more than 25 dB compared to a conventional TMS configuration, resulting in loudness reduction by more than 14-fold. These results motivate improved mechanical design of TMS coils as well as design of TMS pulse generators with shorter pulse durations and increased voltage limits with the objective of reducing TMS acoustic noise while retaining the neurostimulation strength.

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... Instead, some commercial MRIcompatible coils use up to 10 mm of acoustic foam to separate the windings from the exterior, which results in a lower sound level, but still at the price of some loss in maximum output and focality [1], [32]. To further reduce the thickness of the sound insulation, our earlier work suggested impeding the sound transmission with multiple layers of different materials: a stiff winding block in a viscoelastic bed, surrounded by an elastic silicone layer and a stiff outer casing [33]. This approach allowed reduced sound while having separation between the winding and the coil surface (4-6 mm) comparable to the upper range for conventional coils (2-5 mm). ...
... This approach allowed reduced sound while having separation between the winding and the coil surface (4-6 mm) comparable to the upper range for conventional coils (2-5 mm). This coil design was part of our proposed two-pronged approach to "quiet TMS," involving improved electromechanical coil design and the use of briefer pulses [33], [34]. ...
... The potting mold was 3d-printed from nylon 12 (Xometry, USA), and had a minimum wall thickness of 0.7 mm and minimum potting thickness of 1.1 mm (Fig. 2, left). Consequently, the bottom of the coil winding was 1.8 mm above the bottom of the winding block, and the total distance between the center of the coil winding and the coil surface was 7.8 mm, which is comparable with commercial TMS coils [33]. The winding was connected to a commercial TMS device (MagPro R30 incl. ...
Article
This work aims to reduce the acoustic noise level of transcranial magnetic stimulation (TMS) coils. TMS requires high currents (several thousand amperes) to be pulsed through the coil, which generates a loud acoustic impulse whose peak sound pressure level (SPL) can exceed 130 dB(Z). This sound poses a risk to hearing and elicits unwanted neural activation of auditory brain circuits. $Methods$ : We propose a new double-containment coil with enhanced winding mounting (DCC), which utilizes acoustic impedance mismatch to contain and dissipate the impulsive sound within an air-tight outer casing. The coil winding is potted into a rigid block, which is mounted to the outer casing through the block's acoustic nodes that are subject to minimum vibration during the pulse. The rest of the winding block is isolated from the casing by an air gap, and the sound is absorbed by polyester fiber panels within the casing. The casing thickness under the winding center is minimized to maximize the electric field output. $Results$ : Compared to commercial figure-of-eight TMS coils, the DCC prototype has 18–41 dB(Z) lower peak SPL at matched stimulation strength, whilst providing 28% higher maximum stimulation strength than equally focal coils. $Conclusion$ : The DCC design greatly reduces the acoustic noise of TMS while increasing the achievable stimulation strength. $Significance$ : The acoustic noise reduction from our coil design is comparable to that provided by typical hearing protection devices. This coil design approach can enhance hearing safety and reduce auditory co-activations in the brain and other detrimental effects of TMS sound.
... This approach is further supported by the conventional hierarchy of hazard controls, in which personal protective equipment is considered the least effective, last-resort solution [33]. We have proposed a two-pronged approach to quiet TMS, involving improved electromechanical coil design and briefer pulses [34], [35]. In the present work we focus on the first part of this approach and demonstrate a TMS coil design with high electromagnetic output but substantially reduced acoustic emission for conventional TMS pulse waveforms. ...
... The potting mold was 3d-printed from nylon 12 (Xometry, USA), and had a minimum wall thickness of 0.7 mm and minimum potting thickness of 0.8 mm (Fig. 2, left). Consequently, the coil windings were 1.5 mm above the bottom of the winding block, and the total distance between the center of the coil windings and the coil surface was 6.9 mm, which is comparable with commercial TMS coils [34]. The winding was connected to a commercial TMS device (MagPro X100 incl. ...
... We presented a new coil design to reduce the sound of TMS. This double-containment coil design (DCC) maximized the mismatch in acoustic impedance in the path between the winding and the casing [34] without increasing significantly the thickness of the acoustic containment structure. This is in contrast to previously suggested TMS sound containments utilizing medium to high vacuum of below 1 Pa [46]. ...
Preprint
Objective: This work aims to reduce the acoustic noise level of transcranial magnetic stimulation (TMS) coils. TMS requires high currents (several thousand amperes) to be pulsed through the coil, which generates a loud acoustic impulse whose peak sound pressure level (SPL) can exceed 130 dB(Z). This sound poses a risk to hearing and elicits unwanted neural activation of auditory brain circuits. Methods: We propose a new double-containment coil with enhanced winding mounting (DCC), which utilizes acoustic impedance mismatch to contain and dissipate the impulsive sound within an air-tight outer casing. The coil winding is potted in a rigid block, which is mounted to the outer casing by its acoustic nodes that are subject to minimum vibration during the pulse. The rest of the winding block is isolated from the casing by an air gap, and sound is absorbed by foam within the casing. The casing thickness under the winding center is minimized to maximize the coil electric field output. Results: Compared to commercial figure-of-eight TMS coils, the DCC prototype has 10-33 dB(Z) lower SPL at matched stimulation strength, whilst providing 22% higher maximum stimulation strength than equally focal commercial coils. Conclusion: The DCC design greatly reduces the acoustic noise of TMS while increasing the achievable stimulation strength. Significance: The acoustic noise reduction from our coil design is comparable to that provided by typical hearing protection devices. This coil design approach can enhance hearing safety and reduce auditory co-activations in the brain and other detrimental effects of TMS sound.
... A microphone was pointed at the center of the head-side of each coil at a distance of 25 cm (see Supplementary Fig. S1B). The 25 cm recording distance was selected to avoid the confounds of spatial fluctuations in the sound near-field [2,15] and to allow removal of the TMS electromagnetic artifact induced into the microphone hardware. The latter was possible since no sound from the coil could arrive at the microphone before about 730 µs-after the end of the TMS electromagnetic pulse. ...
... The E-field was sampled at 100 MHz with an oscilloscope (Tektronix MDO3054, Tektronix, USA). To obtain the effective stimulation strength, the E-field waveform was digitally low-pass filtered with a time constant of 200 µs, corresponding to the approximate strength-duration time constant in primary motor cortex [15,23,24]. The stimulation strength, defined as the absolute peak of the filtered waveform, was then scaled relative to the average resting motor threshold (RMT) by denoting 100% RMT to correspond to 50.3% MSO for the Magstim 70mm Double Coil driven by a Magstim Rapid biphasic stimulator [25]. ...
... Nevertheless, we presented simple scaling to estimate the sound level at distances corresponding to the TMS subject or operator. We chose a measurement distance of 25 cm to avoid either sampling the sound spatial distribution or underestimating the SPL due to measuring near a nodal point of a standing wave pattern in the near field [2,15]. This also enabled temporal separation of the sound waveform from the stimulation artifact induced in the microphone hardware, allowing simple suppression of the latter. ...
Article
Full-text available
Background Accurate data on the sound emitted by transcranial magnetic stimulation (TMS) coils is lacking. Methods We recorded the sound waveforms of seven coils with high bandwidth. We estimated the neural stimulation strength by measuring the induced electric field and applying a strength–duration model to account for different waveforms. Results Across coils, at maximum stimulator output and 25 cm distance, the sound pressure level (SPL) was 98–125 dB(Z) per pulse and 76–98 dB(A) for a 20 Hz pulse train. At 5 cm distance, these values were estimated to increase to 112–139 dB(Z) and 90–112 dB(A), respectively. Conclusions The coils’ airborne sound can exceed some exposure limits for TMS subjects and, in some cases, for operators. These findings are consistent with the current TMS safety guidelines that recommend the use of hearing protection.
... Addressing the need for a TMS device that generates less noise, we are developing quiet TMS (qTMS) that would have substantially lower acoustic noise emission compared to conventional TMS. We reported previously results from a limited-voltage prototype [4]. In this paper, we summarize the qTMS concept and preliminary data, including new illustrative data and analyses, and outline a proposed novel approach to implement qTMS at full output. ...
... The acoustic emissions from the TMS coil can be reduced by engineering three distinct sections of the acoustic pathway from the winding to the coil surface [4]. The acoustic source in a coil is the winding that vibrates due to electromagnetic forces associated with high pulse currents. ...
... We constructed a prototype circular coil as described in [4]. Briefly, the winding has 11 turns and 8 µH inductance. ...
Conference Paper
A significant limitation of transcranial magnetic stimulation (TMS) is that the magnetic pulse delivery is associated with a loud clicking sound as high as 140 dB resulting from electromagnetic forces. The loud noise significantly impedes both basic research and clinical applications of TMS. It effectively makes TMS less focal since every click activates auditory cortex, brainstem, and other connected regions, synchronously with the magnetic pulse. The repetitive clicking sound can induce neuromodulation that can interfere with and confound the intended effects at the TMS target. As well, there are known concerns regarding blinding of TMS studies, hearing loss, induction of tinnitus, as well as tolerability. Addressing this need, we are developing a quiet TMS (qTMS) device that incorporates two key concepts: First, the dominant frequency components of the TMS pulse sound (typically 2-5 kHz) are shifted to higher frequencies that are above the human hearing upper threshold of about 20 kHz. Second, the TMS coil is designed electrically and mechanically to generate suprathreshold electric field pulses while minimizing the sound emitted at audible frequencies (<; 20 kHz). The enhanced acoustic properties of the coil are accomplished with a novel, layered coil design. We summarize a proof-of-concept qTMS prototype demonstrating noise loudness reduction by 19 dB(A) with ultrabrief pulses at conventional amplitudes. Further, we outline next steps to accomplish further sound reduction and suprathreshold pulse amplitudes.
... The combination of these large excitation parameters with low coil resistance produces important heating and acoustic noises in the coil system during the session that can have an impact on the therapy outcome [66]. Increasing the efficiency of the whole device would directly permit the reduction of coil heating, with minimal attenuation of the acoustic noise; nevertheless, this noise still represents a key factor in addressing future developments [75]. ...
... The system proved to be lightweight and capable of producing current densities of 1.9 times the motor threshold. Later, Peterchev et al. [66,75] proposed to reduce the loud sound provoked by the coil during therapies by implementing a double plastic case around the coil to absorb the acoustic waves and reduce the undesired effects that these sounds could have on the therapy. Other groups have proposed adaptations of the TMS devices and coils to provide double-blind sham stimulation [87] by controlling the direction of the electrical current in the coils to deliver either sham or effective (real) therapy [71]. ...
Article
Full-text available
The technology for transcranial magnetic stimulation (TMS) has significantly changed over the years, with important improvements in the signal generators, the coils, the positioning systems, and the software for modeling, optimization, and therapy planning. In this systematic literature review (SLR), the evolution of each component of TMS technology is presented and analyzed to assess the limitations to overcome. This SLR was carried out following the PRISMA 2020 statement. Published articles of TMS were searched for in four databases (Web of Science, PubMed, Scopus, IEEE). Conference papers and other reviews were excluded. Records were filtered using terms about TMS technology with a semi-automatic software; articles that did not present new technology developments were excluded manually. After this screening, 101 records were included, with 19 articles proposing new stimulator designs (18.8%), 46 presenting or adapting coils (45.5%), 18 proposing systems for coil placement (17.8%), and 43 implementing algorithms for coil optimization (42.6%). The articles were blindly classified by the authors to reduce the risk of bias. However, our results could have been influenced by our research interests, which would affect conclusions for applications in psychiatric and neurological diseases. Our analysis indicates that more emphasis should be placed on optimizing the current technology with a special focus on the experimental validation of models. With this review, we expect to establish the base for future TMS technological developments.
... The E-field was sampled at 100 MHz with an oscilloscope (Tektronix MDO3054, Tektronix, USA). To obtain the effective stimulation strength, the E-field waveform was digitally low-pass filtered with a time constant of 200 µs, corresponding to the approximate strength-duration time constant in primary motor cortex [Barker et al., 1991;Peterchev et al., 2013;Goetz et al., 2014]. The stimulation strength, defined as the absolute peak of the filtered waveform, was then scaled relative to the average resting motor threshold (RMT) by denoting 100% RMT to correspond to 50.3% MSO for the Magstim 70mm Double Coil driven by a Magstim Rapid biphasic stimulator [Kammer et al., 2001]. ...
... Our microphone was placed at 25 cm away from the center of the coil, compared to the typical coil-ear distance of about 10 cm. We chose this distance to avoid either (1) having to sample the spatial distribution of the sound or (2) underestimating the SPL due to measuring near a nodal point of a standing wave pattern in the near field [Goetz et al., 2014;Goetz et al., 2015]. The sound pressure from TMS coils decays approximately inversely to the distance down to 5 cm [Starck et al. 1996], which suggests that the typical SPL at 5 cm and 10 cm from the coils is respectively about 14 dB and 8 dB higher than the SPL measured at 25 cm. ...
Preprint
Background: Accurate data on the sound emitted by various transcranial magnetic stimulation (TMS) coils is lacking. Methods: We recorded the coil sound waveforms of seven coils. We estimated the neural stimulation strength by measuring the induced electric field and applying a strength-duration model to account for different waveforms. Results: At typical resting motor threshold (RMT), sound pressure level (SPL) at a distance of 25 cm varied 87-111 dB(Z) across coils and the sound duration ranged 1-16 ms. At maximum stimulator output and 5-cm distance, SPL is estimated to be 110-139 dB(Z), and a 10-Hz-train of repetitive TMS (rTMS) would produce a continuous sound level of 87-109 dB(A). Conclusions: The sound of all tested coils was below, but near, relevant safety limits. The safety standards may be inadequate for risks specific to TMS. Therefore, we recommend hearing protection during TMS.
... This hypothesis was supported by a simulation study of transcranial electrical stimulation that modeled the activation thresholds for motor cortex pyramidal axons and scalp Aδ nociceptor fibers [18]. Furthermore, briefer pulses decrease the coil energy [19,20] and the coil acoustic output, reducing the loudness [21] and possibly the mechanical tapping as well. ...
... Indeed, the lack of effect of pulse width on the perceived strength of stimulation supports a similar time constant for this aspect of sensation as for motor cortex activation. Apparently, the perception of strength was not affected by the reduction of coil energy [20] and acoustic output [21] for briefer pulses, suggesting that these contributions may be insignificant. On the other hand, the different audible pitch of the pulses, which is higher for briefer widths [32], may have modulated the perception of stimulation, resulting in sharper sensation associated with briefer pulses. ...
Article
Background: Scalp sensation and pain comprise the most common side effect of transcranial magnetic stimulation (TMS), which can reduce tolerability and complicate experimental blinding. Objective: We explored whether changing the width of single TMS pulses affects the quality and tolerability of the resultant somatic sensation. Methods: Using a controllable pulse parameter TMS device with a figure-8 coil, single monophasic magnetic pulses inducing electric field with initial phase width of 30, 60, and 120 µs were delivered in 23 healthy volunteers. Resting motor threshold of the right first dorsal interosseus was determined for each pulse width, as reported previously. Subsequently, pulses were delivered over the left dorsolateral prefrontal cortex at each of the three pulse widths at two amplitudes (100% and 120% of the pulse-width-specific motor threshold), with 20 repetitions per condition delivered in random order. After each pulse, subjects rated 0-to-10 visual analog scales for Discomfort, Sharpness, and Strength of the sensation. Results: Briefer TMS pulses with amplitude normalized to the motor threshold were perceived as slightly more uncomfortable than longer pulses (with an average 0.89 point increase on the Discomfort scale for pulse width of 30 µs compared to 120 µs). The sensation of the briefer pulses was felt to be substantially sharper (2.95 points increase for 30 µs compared to 120 µs pulse width), but not stronger than longer pulses. As expected, higher amplitude pulses increased the perceived discomfort and strength, and, to a lesser degree the perceived sharpness. Conclusions: Our findings contradict a previously published hypothesis that briefer TMS pulses are more tolerable. We discovered that the opposite is true, which merits further study as a means of enhancing tolerability in the context of repetitive TMS.
... These conventional devices deploy a pulse generator circuit consisting essentially of an energy storage capacitor and a thyristor switch that can be triggered to discharge the capacitor into the stimulation coil but cannot be controllably turned off to shape the pulse. More flexible control of the pulse shape could potentially enable a host of research and clinical applications that are not feasible with available TMS devices, including expanded characterization of neural properties, more selective targeting of neural populations, enhanced neuromodulation effectiveness and reproducibility, reduced energy use and coil heating, as well as mitigation of pulse sensation and sound [11][12][13][14][15][16] (see also section 5). ...
... targeting [10,39,40], and mitigate TMS side effects such as the pulse sensation and sound [16,41]. ...
Article
Objective: This work aims at flexible and practical pulse parameter control in transcranial magnetic stimulation (TMS), which is currently very limited in commercial devices. Approach: We present a third generation controllable pulse parameter device (cTMS3) that uses a novel circuit topology with two energy-storage capacitors. It incorporates several implementation and functionality advantages over conventional TMS devices and other devices with advanced pulse shape control. cTMS3 generates lower internal voltage differences and is implemented with transistors with a lower voltage rating than prior cTMS devices. Main results: cTMS3 provides more flexible pulse shaping since the circuit topology allows four coil-voltage levels during a pulse, including approximately zero voltage. The near-zero coil voltage enables snubbing of the ringing at the end of the pulse without the need for a separate active snubber circuit. cTMS3 can generate powerful rapid pulse sequences (< 10 ms inter pulse interval) by increasing the width of each subsequent pulse and utilizing the large capacitor energy storage, allowing the implementation of paradigms such as paired-pulse and quadripulse TMS with a single pulse generation circuit. cTMS3 can also generate theta (50 Hz) burst stimulation with predominantly unidirectional electric field pulses. The cTMS3 device functionality and output strength are illustrated with electrical output measurements as well as a study of the effect of pulse width and polarity on the active motor threshold in ten healthy volunteers. Significance: The cTMS3 features could extend the utility of TMS as a research, diagnostic, and therapeutic tool.
... Stimulation with pulses of different durations demonstrated that pulse shapes also affect a subject's or patient's perception of the pulse on the scalp, likely due to the different activation dynamics of nociceptors and other sensory fibers in the skin compared to the various cortical neurons [74]. Pulses with the majority of their spectral content in higher frequency ranges emit less sound, which is more than just a technical nuisance and artifact of TMS as it concur-rently stimulates auditory circuits [75][76][77][78][79][80]. The loud clicking sound of pulses could previously not be isolated from the electromagnetic stimulation and is always exactly in sync with it. ...
Preprint
The temporal shape of a pulse in transcranial magnetic stimulation (TMS) influences which neuron populations are activated preferentially as well as the strength and even direction of neuromodulation effects. Furthermore, various pulse shapes differ in their efficiency, coil heating, sensory perception, and clicking sound. However, the available TMS pulse shape repertoire is still very limited to a few pulses with sinusoidal or near-rectangular shapes. Monophasic pulses, though found to be more selective and stronger in neuromodulation, are generated inefficiently and therefore only available in simple low-frequency repetitive protocols. Despite a strong interest to exploit the temporal effects of TMS pulse shapes and pulse sequences, waveform control is relatively inflexible and only possible parametrically within certain limits. Previously proposed approaches for flexible pulse shape control, such as through power electronic inverters, have significant limitations: Existing semiconductor switches can fail under the immense electrical stress associated with free pulse shaping, and most conventional power inverter topologies are incapable of generating smooth electric fields or existing pulse shapes. Leveraging intensive preliminary work on modular power electronics, we present a modular pulse synthesizer (MPS) technology that can, for the first time, flexibly generate high-power TMS pulses with user-defined electric field shape as well as rapid sequences of pulses with high output quality. The circuit topology breaks the problem of simultaneous high power and switching speed into smaller, manageable portions. MPS TMS can synthesize practically any pulse shape, including conventional ones, with fine quantization of the induced electric field.
Article
The temporal shape of a pulse in transcranial magnetic stimulation (TMS) influences which neuron populations are activated preferentially as well as the strength and even direction of neuromodulation effects. Furthermore, various pulse shapes differ in their efficiency, coil heating, sensory perception, and clicking sound. However, the available TMS pulse shape repertoire is still very limited to a few biphasic, monophasic, and polyphasic pulses with sinusoidal or near-rectangular shapes. Monophasic pulses, though found to be more selective and stronger in neuromodulation, are generated inefficiently and therefore only available in simple low-frequency repetitive protocols. Despite a strong interest to exploit the temporal effects of TMS pulse shapes and pulse sequences, waveform control is relatively inflexible and only possible parametrically within certain limits. Previously proposed approaches for flexible pulse shape control, such as through power electronic inverters, have significant limitations: Existing semiconductor switches can fail under the immense electrical stress associated with free pulse shaping, and most conventional power inverter topologies are incapable of generating smooth electric fields or existing pulse shapes. Leveraging intensive preliminary work on modular power electronics, we present a modular pulse synthesizer (MPS) technology that can, for the first time, flexibly generate high-power TMS pulses (~ 4,000 V, ~ 8,000 A) with user-defined electric field shape as well as rapid sequences of pulses with high output quality. The circuit topology breaks the problem of simultaneous high power and switching speed into smaller, manageable portions, distributed across several identical modules. In consequence, MPS TMS can use semiconductor devices with voltage and current ratings lower than the overall pulse voltage and distribute the overall switching of several hundred kilohertz among multiple transistors. MPS TMS can synthesize practically any pulse shape, including conventional ones, with fine quantization of the induced electric field. Moreover, the technology allows optional symmetric differential coil driving so that the average electric potential of the coil, in contrast to conventional TMS devices, stays constant to prevent capacitive artifacts in sensitive recording amplifiers, such as electroencephalography (EEG). MPS TMS can enable the optimization of stimulation paradigms for more sophisticated probing of brain function as well as stronger and more selective neuromodulation, further expanding the parameter space available to users.
Article
This paper presents a novel transcranial magnetic stimulation (TMS) pulse generator with a wide range of pulse shape, amplitude, and width. Approach: The novel MM-TMS device is the first to use a modular multi-level circuit topology at full TMS energy levels. It consists of ten cascaded H-bridge modules, each implemented with insulated-gate bipolar transistors, enabling both novel high-amplitude ultrabrief pulses as well as pulses with conventional amplitude and duration. The MM-TMS device has 21 available output voltage levels within each pulse, allowing flexible synthesis of various pulse waveforms and sequences. The circuit further allows charging the energy storage capacitor on each of the ten cascaded modules with a conventional TMS power supply. Main results: The MM-TMS device can output peak coil voltages and currents of 11 kV and 10 kA, respectively, enabling ultrabrief suprathreshold pulses (> 8.25 μs active electric field phase). Further, the MM-TMS device can generate a wide range of near-rectangular monophasic and biphasic pulses, as well as more complex sinusoidal, polyphasic, and amplitude-modulated pulses. At matched estimated stimulation strength, briefer pulses emit less sound, which could enable quieter TMS. Finally, the MM-TMS device can instantaneously increase or decrease the amplitude from one pulse to the next by adding or removing modules in series, which enables rapid pulse sequences and paired-pulse protocols with various pulse shapes. Significance: The MM-TMS device allows unprecedented control of the pulse characteristics which could enable novel protocols and quieter operation.
Article
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.
Article
Transcranial magnetic stimulation (TMS) has been proved to be effective in the treatment of many psychiatric disorders, but the clicking noise produced by the large and short pulse current in the TMS coil may put negative effect to the hearing of patients. However, current researches on noise control of the TMS device are very limited. In this paper, by analyzing the actual noise signal of TMS, the mechanism of noise generation of the device is explained. According to the therapeutic schedule of TMS, an active noise control (ANC) strategy for TMS device with online identification, offline analysis, and real-time output is proposed. A finite element analysis model of noise propagation and noise control of the device is established. The strategy steps are as follows: the secondary pathway is constructed at first; during the first stimulation sequence, the coil noise received by the human ear is collected in real-time, and the noise is analyzed offline; the secondary signal is then produced to reduce the following noise in real-time. The simulation results show that the proposed ANC strategy for TMS can effectively reduce the noise with certain robustness.
Article
A novel method for obtaining superior intracranial focusing field in transcranial magnetic stimulation is proposed in this paper. In order to improve stimulation intensity and focalization, a semi-ellipse coil pair (SEP) of special coil configuration is de-signed and introduced. Projected onto a plane parallel to stimu-lating target, the two adjacent coils are in semi-ellipse shape. From the front view, the SEP is bended along a symmetrical axis at specific an-gles. Finite-element method is adopted to analyze the relations between the geometric structure characteristics of SEP and the 3D spatial distributions of the induced electromagnetic field pro-duced by SEP. The SEP coil is compared to a conventional figure of eight coil by the positive peak value of intracranial induced electrical field and the focusing area at a target plane located 20mm below the scalp. Results indicate that under similar power loss, the design of SEP makes it possible to enhance the positive peak value of induced electrical field and decrease the fo-cusing area simultaneously. A real human head modeled as ho-mogeneous and isotropic is occupied in this paper to verify our method.
Article
Magnetic stimulation is a non-invasive neurostimulation technique that can evoke action potentials and modulate neural circuits through induced electric fields. Biophysical models of magnetic stimulation have become a major driver for technological developments and the understanding of the mechanisms of magnetic neurostimulation and neuromodulation. Major technological developments involve stimulation coils with different spatial characteristics and pulse sources to control the pulse waveform. While early technological developments were the result of manual design and invention processes, there is a trend in both stimulation coil and pulse source design to mathematically optimize parameters with the help of computational models. To date, macroscopically highly realistic spatial models of the brain, as well as peripheral targets, and user-friendly software packages enable researchers and practitioners to simulate the treatment-specific and induced electric field distribution in the brains of individual subjects and patients. Neuron models further introduce the microscopic level of neural activation to understand the influence of activation dynamics in response to different pulse shapes. A number of models that were designed for online calibration to extract otherwise covert information and biomarkers from the neural system recently form a third branch of modelling.
Article
Full-text available
The present invention relates to a stimulator head of a magnetic stimulator used in the stimulation of living tissue such as the human brain. Such a stimulator bead comprises a stimulator head body (3) suited for mounting the stimulator head on the magnetic stimulator equipment, at least one coil (1) which is connected to said stimulator head body (3) and is designed suitable for generating a stimulating magnetic field, and conductors (7) for passing electric current from said magnetic stimulator into any of said at least one coil (1). According to the invention, the stimulator head includes a housing (2) which is connected to said stimulator head body (3) and is designed to enclose at least one air-tight space (5) which further separates each of said at least one stimulator coil (1) from the other parts of said housing (2) facing the object being stimulated. Further according to the invention, each of said at least one coil (1) is placed in said housing (2), whereby an acoustic insulation can be attained between each of said at least one coil (1) and the object being stimulated by virtue of bringing the pressure in said air-tight space (5) to a substantially low level.
Article
This paper introduces a novel modular multilevel series/parallel converter that allows switching modules dynamically not only in series, as in the traditional modular multilevel converter (M2C), but also in parallel. As in M2C, the semiconductor voltages do not exceed the module capacitor voltage for any module state. While the new topology is a generalization of M2C and could, therefore, be operated identically to it, the additional states provide degrees of freedom that the controller can dynamically employ to achieve several advantages. Whereas in M2C many modules are bypassed if the instantaneous converter voltage is lower than the system's peak voltage, the parallel connectivity enables these modules to contribute to the current load, thus reducing conduction losses. In addition, the parallel configuration of modules can be used for balancing the modules’ state of charge (SOC). The parallelization losses are moderate or negligible, dependent on the switching rate. Since the parallel connection of capacitors can ensure balancing, it enables stable operation of a multilevel converter without the need for monitoring the module SOCs. While such economical control hardware may be appropriate for low-power systems, we also present more sophisticated control that uses the additional degrees of freedom to minimize losses. Finally, we point to further extensions of the circuit topology to multipole module connectivity that could enable additional functionality and applications.
Article
Objective: To demonstrate the use of a novel controllable pulse parameter TMS (cTMS) device to characterize human corticospinal tract physiology. Methods: Motor threshold and input-output (IO) curve of right first dorsal interosseus were determined in 26 and 12 healthy volunteers, respectively, at pulse widths of 30, 60, and 120 μs using a custom-built cTMS device. Strength-duration curve rheobase and time constant were estimated from the motor thresholds. IO slope was estimated from sigmoid functions fitted to the IO data. Results: All procedures were well tolerated with no seizures or other serious adverse events. Increasing pulse width decreased the motor threshold and increased the pulse energy and IO slope. The average strength-duration curve time constant is estimated to be 196 μs, 95% CI [181 μs, 210 μs]. IO slope is inversely correlated with motor threshold both across and within pulse width. A simple quantitative model explains these dependencies. Conclusions: Our strength-duration time constant estimate compares well to published values and may be more accurate given increased sample size and enhanced methodology. Multiplying the IO slope by the motor threshold may provide a sensitive measure of individual differences in corticospinal tract physiology. Significance: Pulse parameter control offered by cTMS provides enhanced flexibility that can contribute novel insights in TMS studies.
Article
Magnetic stimulation pulse sources are very inflexible high-power devices. The incorporated circuit topology is usually limited to a single pulse type. However, experimental and theoretical work shows that more freedom in choosing or even designing waveforms could notably enhance existing methods. Beyond that, it even allows entering new fields of application. We propose a technology that can solve the problem. Even in very high frequency ranges, the circuitry is very flexible and is able generate almost every waveform with unrivaled accuracy. This technology can dynamically change between different pulse shapes without any reconfiguration, recharging or other changes; thus the waveform can be modified also during a high-frequency repetitive pulse train. In addition to the option of online design and generation of still unknown waveforms, it amalgamates all existing device types with their specific pulse shapes, which have been leading an independent existence in the past years. These advantages were achieved by giving up the common basis of all magnetic stimulation devices so far, i.e., the high-voltage oscillator. Distributed electronics handle the high power dividing the high voltage and the required switching rate into small portions.
Book
BewitchedSimon the Loyal has vowed never to love, for love makes a warrior weak. His arranged marriage to a beautiful Norman heiress would be duty and no more. But more than duty stirs his blood when he first sees Ariane.BetrayedShe has known only coldness from men - and a betrayal so deep it all but killed her soul. Wanting no man, trusting no man, speaking only through the sad songs she draws from her harp, Ariane comes to Simon an unwilling bride.EnchantedThey wed to bring peace to the Disputed Lands, but marriage alone is not enough. Simon must teach Ariane passion, she must teach him trust. And both must surrender to the sweet violence of love's enchantment. . .or die. © Springer-Verlag Berlin Heidelberg 1990, 1999, 2007. All rights are reserved.
Article
The guidelines for use of repetitive transcranial magnetic stimulation (rTMS) advise frequent updating of rTMS safety guidelines and recommendations. Although rTMS can produce sound of more than 120 dB C, which is sufficient to induce hearing loss, the effect of rTMS noise on the hearing of both patients and rTMS practitioners is understudied. This study investigated the effects of rTMS noise on subjects' hearing using otoacoustic emissions evoked by clicks (transiently evoked otoacoustic emissions, TEOAEs), which is an objective and sensitive method of cochlear exploration. Hearing thresholds and TEOAEs were recorded in 24 normal-hearing healthy subjects before and after a real or sham rTMS session (a single 20-minute session applied to the superior temporal gyrus with 1200 pulses at 100% of the individual motor threshold). No significant difference in hearing thresholds was observed between subjects exposed to real or sham rTMS. However, the difference in TEOAE amplitude between pre- and post-rTMS sessions increased significantly with rTMS noise for those subjects the least protected by earplugs, showing a post-rTMS slight decrease of TEOAE amplitude for high rTMS intensities and hence minor hearing function alteration. However, this correlation was no longer found 1 hour after the rTMS session. These findings suggest that, even when rTMS is used within normal safety limits and with good hearing protection, rTMS noise can transiently disturb hearing mechanisms in normal-hearing healthy subjects. This transient effect of rTMS on hearing may be an important consideration for Institutional Review Boards when rTMS is used at higher stimulation intensities.
Article
The characteristics of transcranial magnetic stimulation (TMS) pulses influence the physiological effect of TMS. However, available TMS devices allow very limited adjustment of the pulse parameters. We describe a novel TMS device that uses a circuit topology incorporating two energy storage capacitors and two insulated-gate bipolar transistor (IGBT) modules to generate near-rectangular electric field pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable pulse parameter TMS (cTMS) device can induce electric field pulses with phase widths of 10-310 µs and positive/negative phase amplitude ratio of 1-56. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation up to 82% and 57% and decreases coil heating up to 33% and 41%, respectively. We demonstrate repetitive TMS trains of 3000 pulses at frequencies up to 50 Hz with electric field pulse amplitude and width variability less than the measurement resolution (1.7% and 1%, respectively). Offering flexible pulse parameter adjustment and reduced power consumption and coil heating, cTMS enhances existing TMS paradigms, enables novel research applications and could lead to clinical applications with potentially enhanced potency.
Article
Identification of trigger factors or precipitants is frequently recommended as a basic strategy in the treatment of migraine and tension-type headache (TTH). Trigger factors increase the probability of headache in the short term. Potential trigger factors have been examined most frequently in migraine and less often in TTH. Many of these factors are related to migraine as well as to TTH, but their prevalence may differ in the two headache types. In this chapter, we will review the findings of retrospective as well as of prospective and controlled studies. Taken together, virtually all aspects of life have been suspected to trigger migraine or TTH, but scientific evidence for many of these triggers is poor. Menstruation has a prominent unfavorable role in migraine and possibly in TTH. There is at least some evidence that environmental factors such as weather, lights, noise and odors, stress and other psychological factors, sleeping problems, fatigue and tiredness may play a role. In addition, intake of alcohol, caffeine withdrawal, skipping meals, and possibly dehydration may trigger migraine and TTH in some patients. Scientific evidence is lacking that any other food or food additive plays a relevant role as a trigger factor of headaches.
Article
Electromagnetic-based methods of stimulating brain activity require invasive procedures or have other limitations. Deep-brain stimulation requires surgically implanted electrodes. Transcranial magnetic stimulation does not require surgery, but suffers from low spatial resolution. Optogenetic-based approaches have unrivaled spatial precision, but require genetic manipulation. In search of a potential solution to these limitations, we began investigating the influence of transcranial pulsed ultrasound on neuronal activity in the intact mouse brain. In motor cortex, ultrasound-stimulated neuronal activity was sufficient to evoke motor behaviors. Deeper in subcortical circuits, we used targeted transcranial ultrasound to stimulate neuronal activity and synchronous oscillations in the intact hippocampus. We found that ultrasound triggers TTX-sensitive neuronal activity in the absence of a rise in brain temperature (<0.01 degrees C). Here, we also report that transcranial pulsed ultrasound for intact brain circuit stimulation has a lateral spatial resolution of approximately 2 mm and does not require exogenous factors or surgical invasion.
Article
This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.
An intense impulse noise artifact is generated by the coil used in extracranial magnetic stimulation (EMS) of the brain and cranial nerves. In this study we measured and analyzed the sound pressure level (SPL), spectral content, wave form, and time course of the magnetic coil acoustic artifact (MCAA) impulse noise in the sound field and in the ear canal of life-size models of the human cranium. Two different clinical magnetic stimulators and coils were used. Sound field measurements from both coils showed the MCAA to be a transient impulse noise with a rapid rise-time, brief duration, broad acoustic spectrum, and high intensity. Measurements made on models of the human head with the magnetic coils positioned at selected standard clinical positions for EMS, particularly the peripheral facial nerve, auricle and mastoid areas, indicated that the MCAA may reach sound pressure levels that exceed noise damage-risk criteria limits for sensorineural hearing loss. The maximum peak energy in the acoustic spectrum of the MCAA measured in the ear canal of the model heads was from 2 to 5 kHz, the range of highest sensitivity in human ears. Ear protectors were found to attenuate the SPL of the MCAA, reaching the ear canal of the model heads by 15-22 dB SPL, and were recommended for use by patients and subjects exposed to EMS.
The effects of the magnetic coil acoustic artifact (MCAA) associated with extracranial magnetic field stimulation (EMFS) of the brain were studied in normal hearing rabbits. Spectral and intensity analyses showed that the MCAA is a high intensity transient signal with peak energy between 2 and 5 kHz, and peak amplitudes in the first 100-200 mu sec. At EMFS levels of 50-100% of maximum output (2.0 Tesla), the corresponding MCAA levels were 131-142 dB sound pressure level (peak hold) at the outer ear and amplified by the external meatus to reach 145-157 dB sound pressure level (SPL) at the position of the tympanic membrane in rabbits. Measurements of the acoustic middle ear muscle reflex (AMR) in non-anesthetized rabbits indicated that exposure to EMFS levels of 50-100% resulted in correspondingly increasing compound threshold shifts (CTS) and permanent threshold shifts (PTS) in the unprotected ears of the experimental animals. Auditory brain-stem responses (ABR) measures on the same and additional animals corroborated these findings. Morphological studies showed evidence of substantial cochlear trauma at EMFS levels as low as 50%, with increasing severity up to 100% EMFS. Morphological examination of inner ear structures following exposure to the MCAA in the acute preparation (fixed within hours after exposure) showed ruptures between pillar cells and a detached organ of Corti. Preparations examined 3 or more weeks after exposure showed damaged pillar cells, a widespread loss of outer hair cells, fused and fractured inner hair cell stereocilia, and kinocilium outgrowth on inner hair cells. Although this extremely short impulse contains approximately 2 orders of magnitude less acoustic energy than a continuous noise exposure of 131 dB for 15 min, it is substantially more injurious to the cochlea. The present findings suggest that the acoustic artifact produced by the EMFS coil in some clinical instruments may pose a potential risk for temporary and permanent hearing loss in patients and clinicians when held in close proximity to the unprotected ear. Initial studies suggest that the magnetic field alone did not appear to cause permanent hearing impairment. We recommend the use of ear protectors for the patient and clinician during EMFS as a precautionary measure to prevent possible hearing loss from the MCAA.
Article
The stimulating coil used in extracranial magnetic field stimulation (EMFS) emits a high intensity impulse sound artifact that causes permanent threshold shifts in the unprotected ears of experimental animals. At magnetic stimulation levels of 50 to 100%, the magnetic coil acoustic artifact (MCAA) ranged from 145 to 157 dB peak sound pressure level at the eardrum. The magnetic field alone did not appear to cause hearing impairment since no threshold shifts were observed in ears that were plugged with ear protectors during exposure to the MCAA. These findings suggest that the acoustic artifact produced by EMFS in the clinic may pose some risk for hearing loss in patients and clinicians when held in close proximity to the unprotected ear. We recommend the use of ear protectors for the patient and clinician during EMFS as a precautionary measure to prevent hearing loss.
Article
The long term effects of transcranial electromagnetic stimulation (TEMS) on auditory brainstem and cortical evoked responses and on neuroanatomical structures in the auditory tract were investigated over a 12 month period in rabbits exposed to 1000 stimuli at 100% maximum stimulation level (2.0 tesla instrument output) with a clinical magnetic coil positioned over the cranium. (1) The tone and click audiograms of the pre and post TEMS-exposed plugged ears were normal and did not differ significantly, suggesting that the protected cochlea is unaffected by TEMS. (2) The mean absolute and interwave latencies of auditory brainstem evoked responses (ABR) and the peak amplitudes of the vertex positive waves P1, P3, and P4 in the exposed rabbits were within normal limits, and comparable those of the normal, pre-exposed animals. Wave P5 in the exposed animals was more variable and significantly different from the normal data in mean latency and amplitude. (3) The mean latencies and amplitudes of the post exposed cortical (late) auditory evoked responses (CAER) were not significantly different from the non-exposed ears. Light microscopic examination of sections of the cochlear nucleus and inferior colliculus, possible sources of waves P2 and P5, respectively, of the ABR, showed no EMS-related changes in cellular organization or histological damage. In conclusion, no deleterious effects of TEMS were observed on the protected ear or the peripheral and central auditory system of rabbits after extensive exposure to long term, high intensity, low frequency time-varying magnetic field stimulation with a clinical instrument.
Article
Electromagnetic stimulation (EMS) of the brain and the intracranial portion of the facial nerve has become a widely used clinical technique. The high intensity impulse noise acoustic artifact generated by some magnetic coils used in EMS has been shown to cause severe cochlear damage in experimental animals. This damage results in permanent threshold shifts throughout the auditory spectrum of the rabbit. As with other impulse and impact noise signals, the duration of the coil impulse noise is too short to be influenced by the normally protective acoustic middle ear muscle reflex. Artificially activating the acoustic reflex with a contralateral broad band noise during exposure to the intense coil artifact reduced the compound threshold shift (CTS) significantly, and the permanent threshold shifts (PTS) to near zero at each tone frequency and noise band tested. The results demonstrate the effectiveness of a suprathreshold sound in activating the acoustic middle ear muscle reflex and protecting against impulse noise-induced hearing loss caused by high frequency magnetic coil acoustic impulses.
Article
The noise generated by stimulating coils may jeopardize the hearing of the patients as well as the hearing of the examiner. To evaluate the potential risk caused by the impulse noise of stimulating coils, we examined the A-weighted peak sound pressure levels from five different types of magnetic stimulator coils. At a distance of 10 cm, with 100% stimulation intensity, the coils with Dantec and Magstim stimulators created maximum peak sound pressure levels of 110 dB. Correspondingly, Cadwell MES-10 created maximum peak sound pressure levels of 132 dB. The decrease in the peak levels followed the distance rule quite closely. At a distance of 40 cm, the decrease in peak level was on average 14 dB (range -1-(+)1 dB). Based on American Conference of Governmental Industrial Hygienists (ACGIH) threshold limits of impact noise, the permitted maximum daily number of magnetic stimuli would be 1000 to 10,000. The permitted number of daily stimuli may be difficult to exceed in clinical practice. We consider the risk as small for the patients that are being examined and the operator using magnetic stimulation. The potential risk can be further diminished by even very light weighted hearing protectors providing proper attenuation to the coil impulses.
Article
We have used EEG to measure effects of air- and bone-conducted sound from the coil in transcranial magnetic stimulation (TMS). Auditory-evoked potentials to TMS were recorded in three different experimental conditions: (1) the coil 2 cm above the head, (2) the coil 2 cm above the head but rigidly connected by a plastic piece to the scalp, (3) the coil pressed against the scalp over the motor cortex. The acoustical click from the TMS coil evoked large auditory potentials, whose amplitude depended critically on the mechanical contact of the coil with the head. Both air- and bone-conducted sounds have to be taken into account in the design and interpretation of TMS experiments.
Article
The aim of this study is to describe the variability and other characteristics of the motor evoked potential (MEP) to transcranial magnetic stimulation (TMS) in a large database. One hundred fifty one subjects, including 17 sib pairs, free of neurological or psychiatric disease and on no neuroactive medications were studied with uniform techniques. Nineteen were studied on 3 occasions. Measures included MEP threshold (N=141) during rest and voluntary muscle activation and the response to paired TMS (subthreshold conditioning stimulus) at interstimulus intervals (ISIs) of 3, 4, 10, and 15ms (N=53). There was a large variability in all the measures. Approximately 40-50% of this appeared to come from within-subjects variation or experimental error. The MEP threshold data were skewed downward, but normalized with log transformation. The paired-pulse ratios (conditioned/unconditioned MEP) were normally distributed except those from the 3ms ISI which had no lower tail and could not be normalized. There were subjects showing inhibition and others showing facilitation at all ISIs. There were no correlations in any of the data with age or sex, but MEP thresholds were highly correlated within sibs. These data should be useful for planning, analyzing, and interpreting TMS studies in healthy and patient populations.
Article
Noninvasive magnetic stimulation of the human central nervous system has been used in research and the clinic for several years. However, the coils used previously stimulated mainly the cortical brain regions but could not stimulate deeper brain regions directly. The purpose of the current study was to develop a coil to stimulate deep brain regions. Stimulation of the nucleus accumbens and the nerve fibers connecting the prefrontal cortex with the nucleus accumbens was one major target of the authors' coil design. Numeric simulations of the electrical field induced by several types of coils were performed and accordingly an optimized coil for deep brain stimulation was designed. The electrical field induced by the new coil design was measured in a phantom brain and compared with the double-cone coil. The numeric simulations show that the electrical fields induced by various types of coils are always greater in cortical regions (closer to the coil placement); however, the decrease in electrical field within the brain (as a function of the distance from the coil) is markedly slower for the new coil design. The phantom brain measurements basically confirmed the numeric simulations. The suggested coil is likely to have the ability of deep brain stimulation without the need to increase the intensity to levels that stimulate cortical regions to a much higher extent and possibly cause undesirable side effects.
Article
Standard coils used in research and the clinic for noninvasive magnetic stimulation of the human brain are not capable of stimulating deep brain regions directly. As the fields induced by these coils decrease rapidly as a function of depth, only very high intensities would allow functional stimulation of deep brain regions and such intensities would lead to undesirable side effects. We have designed a coil based on numerical simulations and phantom brain measurements that allows stimulation of deeper brain regions, termed the Hesed coil (H-coil). In the present study we tested the efficacy and some safety aspects of the H-coil on healthy volunteers. The H-coil was compared to a regular figure-8 coil in 6 healthy volunteers by measuring thresholds for activation of the abductor pollicis brevis (APB) representation in the motor cortex as a function of distance from each of the coils. The rate of decrease in the coil intensity as a function of distance is markedly slower for the H-coil. The motor cortex could be activated by the H-coil at a distance of 5.5 cm compared to 2 cm with the figure-8 coil. The present study indicate that the H-coil is likely to have the ability of deep brain stimulation and without the need of increasing the intensity to extreme levels that would cause a much greater stimulation in cortical regions. The ability of non-invasive deep brain stimulation potentially opens a wide range of both research and therapeutic applications.
Article
Functional magnetic resonance imaging (fMRI) studies in humans have hitherto failed to demonstrate activity changes in the direct vicinity of transcranial magnetic stimulation (TMS) that cannot be attributed to re-afferent somatosensory feedback or a spread of excitation. In order to investigate the underlying activity changes at the site of stimulation as well as in remote connected regions, we applied short trains of high-intensity (110% of resting motor threshold) and low-intensity (90% of active motor threshold) repetitive TMS (rTMS; 3 Hz, 10 s duration) over the presumed location of the left dorsal premotor cortex (PMd) during fMRI. Signal increases in the direct vicinity of the stimulated PMd were observed during rTMS at 110% RMT. However, positive BOLD MRI responses were observed with rTMS at both 90% and 110% RMT in connected brain regions such as right PMd, bilateral PMv, supplementary motor area, somatosensory cortex, cingulate motor area, left posterior temporal lobe, cerebellum, and caudate nucleus. Responses were generally smaller during low-intensity rTMS. The results indicate that short trains of TMS can modify local hemodynamics in the absence of overt motor responses. In addition, premotor rTMS cannot only effectively stimulate cortico-cortical but also cortico-subcortical connections even at low stimulation intensities.
Article
High-frequency, repetitive, auditory stimulation was used to determine whether induction of a long-lasting increase of the human auditory evoked potential (AEP) was possible. Recording non-invasively with electroencephalogram scalp electrodes, stable increases in amplitude were observed in the N1 component of the AEP, which is thought to reflect activity within auditory cortex (N1). The increase was maintained over an hour and was shown to be independent of alterations in the state of arousal. This is the first demonstration of the induction of long-lasting plastic changes in AEPs, and suggest that this represents the first direct demonstration of long-term potentiation in the auditory cortex of normal, intact humans.
Article
Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge. Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.
Article
Electroencephalographic (EEG) responses measured simultaneously with transcranial magnetic stimulation (TMS) have opened a new window into the human nervous system. The combined use of TMS and EEG (TMS-EEG) provides a means for the detailed study of the reactivity of any cortical region in the intact brain; also the reactivities of non-motor cortical areas related with higher-order functions are now appreciable. A recent epochal finding concerning cortical reactivity is that neuronal activation is induced with remarkably low stimulation intensities. This knowledge is significant when optimizing experimental set-ups for maximal patient safety. Stimulation of different cortical areas evokes different patterns of remote EEG activity, confirming the viability of TMS-EEG for the study of corticocortical connections. In this review, we expand on these and other notable findings related with TMS-EEG. We discuss the possibilities of the technique for the study of cortical reactivity and connectivity. We show that TMS-EEG allows the study of interhemispheric connections with high spatiotemporal specificity and the assessment of cortical reactivity with excellent sensitivity.
Article
This study investigated how triggers acquire the capacity to precipitate headaches. Traditional clinical advice is that the best way to prevent headache/migraine is to avoid the triggers. Avoidance of anxiety-eliciting stimuli, however, results in sensitization to the stimuli, so is there a danger that avoidance of migraine/headache triggers results in decreased tolerance for the triggers? One hundred and fifty subjects, 60 of whom suffered from regular headaches, were randomly assigned to 5 experimental conditions, defined by length of exposure to the headache trigger of noise. Subjects attended a laboratory session divided into 3 phases: preintervention test, intervention (1 of 5 levels of exposure to the trigger), and postintervention test. Response to the intervention was measured in terms of noise tolerance, sensitivity to noise, and nociceptive response to noise. A curvilinear relationship was found between length of exposure to the trigger and pain response for individuals who do not suffer from regular headaches, that is, short exposure was associated with sensitization and prolonged exposure with desensitization. The relationship for headache patients was less clear. The findings are consistent with the proposition that 1 etiological pathway to suffering from frequent headaches is via trying to avoid, or escape from, potential trigger factors. These results suggest that the traditional clinical advice to headache patients, that the best way to prevent migraine/headache is to avoid the triggers, runs the risk of establishing an insidious sensitization process thereby increasing headache frequency.
Article
Previously we have shown that rapid sensory stimulation, in this case, auditory tone pips, can induce long-lasting plastic changes akin to Long Term Potentiation (LTP) within adult human sensory cortex. In a previous study, auditory LTP was reflected as an increase in the amplitude of the N1 component of the auditory event-related potential as measured by EEG. The goal of the present study was to investigate potential effects of LTP-like changes on the hemodynamic response of the human auditory cortex. Silent sparse-sampled fMRI recordings were obtained while subjects passively listened to tone-pips both before and after a short block of rapidly presented auditory tone-pips (auditory tetanus) was delivered. The BOLD response within the primary auditory cortex was significantly enhanced after the auditory tetanus. This is the first study demonstrating LTP-like changes of the hemodynamic response in the auditory system, and thus supports the growing literature demonstrating LTP can be induced in adult human cortex. These results have implications in the fields of perceptual learning and rehabilitation.
Article
Transcranial magnetic stimulation (TMS) has demonstrated efficacy in the treatment of major depressive disorder; however, prior studies have provided only partial safety information. We examined the acute efficacy of TMS in a randomized sham-controlled trial, under open-label conditions, and its durability of benefit. Aggregate safety data were obtained from a comprehensive clinical development program examining the use of TMS in the treatment of major depressive disorder. There were 3 separate clinical protocols, including 325 patients from 23 clinical sites in the United States, Australia, and Canada. Active enrollment occurred between January 2004 and August 2005. Adverse events were assessed at each study visit by review of spontaneous reports with separate reporting of serious adverse events. Safety assessments were also completed for cognitive function and auditory threshold. Assessment of disease-specific risk included the potential for worsening of depressive symptoms. Finally, the time course and accommodation to the most commonly appearing adverse events were considered. TMS was administered in over 10,000 cumulative treatment sessions in the study program. There were no deaths or seizures. Most adverse events were mild to moderate in intensity. Transient headaches and scalp discomfort were the most common adverse events. Auditory threshold and cognitive function did not change. There was a low discontinuation rate (4.5%) due to adverse events during acute treatment. TMS was associated with a low incidence of adverse events that were mild to moderate in intensity and demonstrated a largely predictable time course of resolution. TMS may offer clinicians a novel, well-tolerated alternative for the treatment of major depressive disorder that can be safely administered in an outpatient setting. clinicaltrials.gov Identifier: NCT00104611.
Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research
  • S Rossi
  • M Hallett
  • P M Rossini
  • A Pascual-Leone
Rossi S, Hallett M, Rossini P M, Pascual-Leone A (2009), " Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research, " Clin. Neurophysiol., vol. 120, no. 12, pp. 2008–2039, doi: 10.1016/j.clinph.2009.08.016.