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... These novel pulse shapes can be delivered at both low and high rTMS frequencies. TMS devices with even more flexibility of pulse shaping are under development (Goetz et al., 2015;Peterchev et al., 2015). ...
... These novel pulse shapes can be delivered at both low and high rTMS frequencies. TMS devices with even more flexibility of pulse shaping are under development (Goetz et al., 2015;Peterchev et al., 2015). ...
... There is significant literature on the effects of pulse waveform and E-field direction on the neuromodulatory effect of rTMS (Sommer et al., 2013). Earlier data came from comparisons between conventional biphasic and monophasic pulses (Antal et al., 2002;Arai et al., 2007Arai et al., , 2005Hosono et al., 2008;Sommer et al., 2002;Taylor and Loo, 2007;Tings et al., 2005), whereas more recent studies have used cTMS Peterchev et al., 2015;Goetz et al., 2016). Collectively, these results suggest that TMS pulses with asymmetric E-field phase amplitude -i.e., one phase having significantly larger amplitude than the other, such as in conventional monophasic pulses-confer stronger and direction-specific neuromodulatory effects in rTMS (Halawa et al., 2019). ...
Article
Full-text available
This article is based on a consensus conference, promoted and supported by the International Federation of Clinical Neurophysiology (IFCN), which took place in Siena (Italy) in October 2018. The meeting intended to update the ten-year-old safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings (Rossi et al., 2009). Therefore, only emerging and new issues are covered in detail, leaving still valid the 2009 recommendations regarding the description of conventional or patterned TMS protocols, the screening of subjects/patients, the need of neurophysiological monitoring for new protocols, the utilization of reference thresholds of stimulation, the managing of seizures and the list of minor side effects. New issues discussed in detail from the meeting up to April 2020 are safety issues of recently developed stimulation devices and pulse configurations; duties and responsibility of device makers; novel scenarios of TMS applications such as in the neuroimaging context or imaging-guided and robot-guided TMS; TMS interleaved with transcranial electrical stimulation; safety during paired associative stimulation interventions; and risks of using TMS to induce therapeutic seizures (magnetic seizure therapy). An update on the possible induction of seizures, theoretically the most serious risk of TMS, is provided. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. Finally, new operational guidelines are provided for safety in planning future trials based on traditional and patterned TMS protocols, as well as a summary of the minimal training requirements for operators, and a note on ethics of neuroenhancement.
... 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. ...
... Transcranial magnetic stimulation (TMS) activates cortical neurons by electromagnetically inducing an electric field (E-field) pulse with a coil placed on the subject's scalp. In addition to the desired E-field stimulation, the pulse causes mechanical vibrations in the coil, producing a brief but very loud sound impulse-often referred to as TMS coil click [1,2]. ...
... Due to these side effects, the TMS safety consensus group suggested in 2009 that "the acoustic output of newly developed coils should be evaluated and hearing safety studies should be conducted as indicated by these measures" [4]. Since then, specific stimulator-coil combinations have been evaluated with hearing safety measurements [6,7], and a comparison between coils has been published [2,12]. We extend this previous work by quantifying the impulse characteristics of the airborne TMS sound and comparing the measurements of seven coils at normalized stimulation strengths. ...
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.
... Transcranial magnetic stimulation (TMS) activates cortical neurons by electromagnetically inducing an electric field (E-field) pulse with a coil placed on the subject's scalp. In addition to the desired E-field stimulation, the pulse causes mechanical vibrations in the coil, producing a brief but very loud sound-often referred to as TMS coil click [Counter & Borg, 1992;Goetz et al., 2015]. ...
... Since then, specific stimulator-coil combinations have been evaluated with hearing-safety measurements [Tringali et al., 2012;Kukke et al., 2017], and at least one comparison between coils has been published [Dhamne et al., 2014]. To address methodological limitations of the latter, namely sound level measurements intended only for non-impulsive sounds based on IEC 61672 [Goetz et al., 2015], and expand the range of compared devices, we conducted measurements of the coil click in a total of seven coils for three stimulators and normalized the stimulation strength across the various configurations. Moreover, we interpret the results for single pulses as well as for repetitive TMS (rTMS) in the context of various hearing safety standards. ...
... Choosing an appropriate safety limit for TMS sound is not straightforward: In addition to the common limit of 115 dB(A) time-averaged steady-state sound level for short daily exposure [OSHA1; OSHA2; OSHA3; ACGIH], we must also consider the impulsive nature of the sound, which is similar to a small explosion, e.g., shooting a firearm, in terms of duration and peak intensity [Peterchev et al., 2015]. Consequently, measurement protocols for such sounds should provide good reference for the measurement protocol of TMS sound. ...
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.
... 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. ...
... The loud clicking sound of pulses could previously not be isolated from the electromagnetic stimulation and is always exactly in sync with it. This confounds TMS studies and clinical applications because auditory stimulation is known to have a strong neuromodulatory effect on brain stem and/or neocortical circuits [76,81]. ...
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.
... The amount of sound reaching a patient ear can of course vary and this is due to changing parameters, such as the type of coil, the size of the ear canal, the number and the repetition frequency of TMS pulses, the position and distance of the coil from the meter. 70 Moreover, since the TMS coil typically rests on the head, sound can be conducted through the skull bone and contribute risk which is not quantified with conventional sound measurements. 70,71 After exposure to the TMS stimulus, few adult participants have experienced transient increases in auditory thresh-mous. ...
... 70 Moreover, since the TMS coil typically rests on the head, sound can be conducted through the skull bone and contribute risk which is not quantified with conventional sound measurements. 70,71 After exposure to the TMS stimulus, few adult participants have experienced transient increases in auditory thresh-mous. For these reasons, it is unrealistic to categorise all these variables into new tables. ...
Article
Full-text available
Transcranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is receiving increasingly attentionTranscranial magnetic stimulation (TMS) is a non-invasive method of brain stimulation that is receiving increasingly attentionfor new clinical applications. Through electromagnetic induction cortical activity can be modulated and therapeuticeffects can be achieved in a variety of psychiatric and neurological conditions. According to the World Health Organization(WHO) depression is the most disabling disease in the world and 350 million people suffer from depression globally. Majordepression is the most common disorder to be treated with TMS and the first mental disorder for which TMS received approvalfrom the US Food and Drug Administration (FDA). We here introduce the basic principles of TMS, discuss the latestdata on safety and side effects, and present various TMS treatment protocols as well as treatment response predictors inmajor depressive disorder.
... Neuroimaging data show that magnetic stimulation, even when given at small intensities, induces bilateral activation in the auditory cortex (Bestmann et al. 2004). The auditory activation correlates with the amplitude of the delivered TMS pulse (Goetz et al. 2015). Moreover, auditory stimuli might activate the reticulospinal tract and therefore modulate the excitability of spinal motoneurons (Dean and Baker 2017), which ultimately determines the outcome of TMS on the motor cortex (Burke and Pierrot-Deseilligny 2010). ...
... The use of earplugs for hearing protection is also recommended by The Safety of TMS Consensus Group guidelines (Rossi et al. 2009). Nevertheless, the neuromodulating effect of stimulation noise when TMS is delivered on the motor cortex remains unknown (Goetz et al. 2015) and no studies to date have investigated the effects of masking and attenuating the discharging noise on the recorded MEP within the same stimulation pulse. ...
Article
Full-text available
The amplitude of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) over the motor cortex is influenced by multiple factors. TMS delivery is accompanied by an abrupt clicking noise which can induce a startle response. This study investigated how masking/attenuating the sound produced by the TMS system discharging influences MEP amplitudes. In addition, the effects of increasing the time between consecutive stimuli and of making participants aware of the time at which they would be stimulated were studied. MEPs were recorded from the Flexor Carpi Radialis (FCR) muscle at rest by stimulation at motor threshold (MT), 120% MT and 140% MT intensity. Participants (N = 23) received stimulation under normal (NORMAL) conditions and while: wearing sound-attenuating earmuffs (EAR); listening to white noise (NOISE); the interval between stimuli were prolonged (LONG); stimulation timing was presented on a screen (READY). The results showed that masking ( p = 0.020) and attenuating ( p = 0.004) the incoming sound significantly reduced the amplitude of MEPs recorded across the intensities of stimulation. Increasing the interval between pulses had no effect on the recorded traces if a jitter was introduced ( p = 1), but making participants aware of stimulation timing decreased MEP amplitudes ( p = 0.049). These findings suggest that the sound produced by TMS at discharging increases MEP amplitudes and that MEP amplitudes are influenced by stimulus expectation. These confounding factors need to be considered when using TMS to assess corticospinal excitability.
... Another possible source of sensation is the mechanical vibration (tapping) generated by the electromagnetic forces within the coil, which can activate mechanoreceptors in the scalp [1,9]. Finally, the synchronous auditory stimulation via both bone and air conduction (partially attenuated by earplugs) may modulate the sensation [10]. Any combination of these factors can affect tolerability, and in addition, the sensation of TMS complicates the blinding of subjects to experimental conditions and requires sophisticated sham procedures to replicate the sensation [11,12]. ...
... This could be done by manipulating the influence of the various factors (e.g., by using mechanically damping foam spacers, applying topical anesthetics to the scalp, delivering masking noise with earphones, comparing with electrical scalp stimulation), rating additional dimensions of the sensation, as well as electrophysiological recordings from the scalp. Future studies may also explore even briefer pulses where the mechano-acoustic emission of the coil is reduced further [10,32] and it is unclear if the tendency for increased discomfort would continue. ...
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.
... Furthermore, the clicking of the contactors closing and breaking contact is clearly audible, despite them being located on an elevated platform inside the rack unit. Although this noise was tolerable and nowhere near hazardous levels to the experimental operator, its presence and associated auditory activation could be of concern when stimulating animals with intact auditory system, which might lead to well-synchronized indirect brain stimulation as known from other paradigms (Zaehle et al. 2007;Goetz et al. 2015). ...
Preprint
Objective We present a power electronic system and magnetic nanoparticles for multiplexed magnetogenetic neurostimulation with three channels spanning a wide frequency range and rapid channel switching capability. This enables selective heating of magnetic nanoparticles with different coercivity using various frequency–amplitude combinations of the magnetic field. Such multiplexed operation could provide the technical means for selective magnetogenetic neurostimulation beyond its spatial focality limits. Approach The electronic system uses a hybrid of silicon metal–oxide–semiconductor and gallium-nitride field-effect transistors, which generate the required high-amplitude current up to 500 A in the sub-MHz range and the high-frequency current in the MHz range, respectively. Via three discrete resonance capacitor banks, the system generates an alternating magnetic field in the same liquid-cooled field coil at three distinct frequency channels spanning 50 kHz to 4 MHz. Fast switching between channels is achieved with high-voltage contactors connecting the coil to different capacitor banks. We characterized the system by the output channels’ frequencies, field strength, and switching time, as well as the system’s overall operation stability. Three types of iron oxide nanoparticles with different coercivity are developed to form three magnetothermal channels. Specific absorption rate and infrared thermal imaging measurements are performed with the nanoparticles to characterize their heating and demonstrate selective actuation for all three channels. Main results The system achieved the desired target field strengths for three frequency channels (70 kA/m at 50 kHz, 10 kA/m at 500 kHz, and 1 kA/m at ≥2 MHz), with rapid switching speed between channels on the order of milliseconds. The system can operate continuously for at least two hours at 30% duty cycle with 125 Arms load in the coil, corresponding to a stimulation protocol of cycling the three channels at target strength with 3 s pulses and 7 s interpulse intervals. The nanoparticles were heated with selectivity between 2.3× and 9× for their respective frequency channel. The system’s intended use was thus validated with three distinct channels available for magnetothermal heating. Significance We describe the first combination of a power electronic system and magnetic nanoparticles that achieves three stimulation channels. Selective actuation of nanoparticles is demonstrated for each channel using the same field coil, including a novel composition responding to magnetic fields in the MHz range. This approach could improve the speed and flexibility of frequency-multiplexed magnetogenetic neural stimulation.
... [17,18], which exceeds the 80 dB safety threshold, for 3 seconds. Moreover, conventional sound measurements cannot quantify the bone conduction through skull during rTMS and can underestimate the acoustic artifact [18,19]. The effect of the acoustic artifact induced by rTMS on the subject's ear can be influenced by the simulation intensity, frequency, coil type, stimulation site (proximity to the ear) and pre-existing auditory symptoms (e.g., tinnitus). ...
... Hearing Impairment.: Further, the TMS pulse causes mechanical vibrations in the coil which produce a brief, intense sound impulse, which is often referred to as a TMS coil "click" (Counter & Borg, 1992;Counter et al., 1991;Goetz et al., 2015;Koponen et al., 2020). Exposure to this click during rTMS sessions has even been shown to produce mild hearing loss as reflected by transient increases in auditory threshold (Loo et al., 2001;Pascual-Leone et al., 1992). ...
Article
The expanding legalization of cannabis across the United States is associated with increases in cannabis use, and accordingly, an increase in the number and severity of individuals with cannabis use disorder (CUD). The lack of FDA-approved pharmacotherapies and modest efficacy of psychotherapeutic interventions means that many of those who seek treatment for CUD relapse within the first few months. Consequently, there is a pressing need for innovative, evidence-based treatment development for CUD. Preliminary evidence suggests that repetitive transcranial magnetic stimulation (rTMS) may be a novel, non-invasive therapeutic neuromodulation tool for the treatment of a variety of substance use disorders (SUDs), including recently receiving FDA clearance (August 2020) for use as a smoking cessation aid in tobacco cigarette smokers. However, the potential of rTMS for CUD has not yet been reviewed. This paper provides a primer on therapeutic neuromodulation techniques for SUDs, with a particular focus on reviewing the current status of rTMS research in people who use cannabis. Lastly, future directions are proposed for rTMS treatment development in CUD, with suggestions for study design parameters and clinical endpoints based on current gold-standard practices for therapeutic neuromodulation research.
... Dies ist mit der Situation bei Drahtlosladestationen vergleichbar für die auch die Referenzgrenzwerte überschritten werden, im Gewebe jedoch die Basisgrenzwerte eingehalten sind (Zahner, Fröhlich et al. 2017), (Fröhlich, Zahner et al. 2018 . 2015), (Deng, Lisanby et al. 2013), (Goetz, Lisanby et al. 2015), (Heinrich 2007), (Hug and Roosli 2012), (Kang and Gandhi 2003), (Levkovitz, Isserles et al. 2015), (Markoll, Da Silva Ferreira et al. 2003), (Markov 2007 ...
Technical Report
Full-text available
Das Vorhaben wurde mit Mitteln des Bundesministeriums für Umwelt, Naturschutz und nukleare Sicherheit (BMU) und im Auftrag des Bundesamtes für Strahlenschutz (BfS) durchgeführt.
... A significant limitation of TMS is that the delivery of the magnetic pulse is associated with a loud clicking sound that may exceed 140 dB [1][2][3]. The clicking sound is a fundamental impediment affecting both basic research and clinical applications of TMS. ...
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.
... During a TMS session, the magnetic pulse produces an audible clicking sound, which varies with different coil designs and intensity. (54, 55) Therefore, an additional standard safety precaution for all TMS treatments is the use of earplugs or other hearing protection capable of at least 30 dB sound reduction.(56) Such a precaution eliminates the risk of changes in auditory threshold with treatment for either the patient or the treatment provider. ...
Article
Full-text available
Background: Prefrontal Transcranial Magnetic Stimulation (TMS) therapy repeated daily over 4-6 weeks (20-30 sessions) is US Food and Drug Administration (FDA) approved for treating Major Depressive Disorder in adults who have not responded to prior antidepressant medications. In 2011, leading TMS clinical providers and researchers created the Clinical TMS Society (cTMSs) (www.clinicaltmssociety.org, Greenwich, CT, USA), incorporated in 2013. Methods: This consensus review was written by cTMSs leaders, informed by membership polls, and approved by the governing board. It summarizes current evidence for the safety and efficacy of the use of TMS therapy for treating depression in routine clinical practice. Authors systematically reviewed the published TMS antidepressant therapy clinical trials. Studies were then assessed and graded on their strength of evidence using the Levels of Evidence framework published by the University of Oxford Centre for Evidence Based Medicine. The authors then summarize essentials for using TMS therapy in routine clinical practice settings derived from discussions and polls of cTMSs members. Finally, each summary clinical recommendation is presented with the substantiating peer-reviewed, published evidence supporting that recommendation. When the current published clinical trial evidence was insufficient or incomplete, expert opinion was included when sufficient consensus was available from experienced clinician users among the membership of the cTMSs, who were polled at the Annual Meetings in 2014 and 2015. Conclusions: Daily left prefrontal TMS has substantial evidence of efficacy and safety for treating the acute phase of depression in patients who are treatment resistant or intolerant. Following the clinical recommendations in this document should result in continued safe and effective use of this exciting new treatment modality.
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
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.
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.
Article
Background Repetitive transcranial magnetic stimulation (rTMS) might be a promising technique in treating insomnia. A comprehensive meta-analysis of the available literature is conducted to offer evidence. Objective To evaluate the efficacy and safety of rTMS for insomnia, either as monotherapy or as a complementary strategy. Methods CENTRAL, PubMed, EMBASE, PsycINFO, CINAHL, PEDro, CBM, CNKI, WANFANG, and VIP were searched from earliest record to August 2019. Randomized control trials (RCTs) published in English and Chinese examining effects of rTMS on patients with insomnia were included. Two authors independently completed the article selection, data extraction and rating. Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality of the included studies. The RevMan software was used for meta-analysis. The quality of the evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results A total of 36 trials from 28 eligible studies were included, involving a total of 2357 adult participants (mean age, 48.80 years; 45.33% males). Compared with sham rTMS, rTMS was associated with improved PSQI total score (SMD -2.31, 95% CI -2.95 to -1.66; Z=7.01, P<0.00001) and scores of seven subscales. Compared to other treatment, rTMS as an adjunct to other treatment was associated with improved PSQI total score (SMD -1.44, 95% CI -2.00 to -0.88; Z=5.01, P<0.00001), and may have effects on scores of seven subscales. Compared with other treatment, rTMS was associated with improved Pittsburgh sleep quality index (PSQI) total score (SMD -0.63, 95% CI -1.22 to -0.04; Z=2.08, P=.04), and may have a better score in sleep latency, sleep disturbance and hypnotic using of seven subscales. In the three pair of comparisons, the results for polysomnography (PSG) outcomes were varied. In general, rTMS may improve sleep quality through increasing slow wave and rapid eye movement (REM) sleep. The rTMS group was more prone to headache than the sham or blank control group (RR 1.71, 95% CI 1.03 to 2.85; Z=2.07, P=.04). No severe adverse events were reported. Reporting biases and low and very low grade of some evidences should be considered when interpreting the results of this meta-analysis. Conclusions Our findings indicate that rTMS may be a safe and effective option for insomnia. Further international, multicenter, high-quality RCTs with more objective, quality of life related and follow-up assessments are needed.
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
Purpose: Concerns regarding hearing safety have limited the number of studies using transcranial magnetic stimulation (TMS) in children and young adults. The objective of this study was to examine the safety of TMS with regards to hearing in a group of 16 children and young adults (17.3 ± 4.9 years) with and without brain injury. Methods: Pure-tone hearing thresholds and distortion-product otoacoustic emissions were measured before and after exposure to single- and paired-pulse TMS (1-2 sessions of 149-446 TMS pulses at a median of 49%-100% maximum stimulator output over a 2.2 hours period). Results: No mean change in hearing outcomes was noted. In addition, no clinically significant change in hearing threshold was observed in any participant, and participants did not experience a subjective change in hearing after TMS exposure. Conclusions: Single- and double-pulse TMS administered within the parameters used in this study, which included hearing protection, can be used in children and young adults without impacting hearing. This study provides further evidence for hearing safety after TMS exposure in children and young adults.
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.
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The intensity of sound emanating from the discharge of magnetic coils used in repetitive transcranial magnetic stimulation (rTMS) can potentially cause acoustic trauma. Per Occupational Safety and Health Administration (OSHA) standards for safety of noise exposure, hearing protection is recommended beyond restricted levels of noise and time limits. We measured the sound pressure levels (SPLs) from four rTMS coils with the goal of assessing if the acoustic artifact levels are of sufficient amplitude to warrant protection from acoustic trauma per OSHA standards. We studied the SPLs at two frequencies (5 and 10 Hz), three machine outputs (MO) (60, 80 and 100%), and two distances from the coil (5 and 10 cm). We found that the SPLs were louder at closer proximity from the coil and directly dependent on the MO. We also found that in all studied conditions, SPLs were lower than the OSHA permissible thresholds for short (<15 min) acoustic exposure, but at extremes of use, may generate sufficient noise to warrant ear protection with prolonged (>8 h) exposure.
Article
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Paired associative stimulation (PAS) consisting of repeated application of transcranial magnetic stimulation (TMS) pulses and contingent exteroceptive stimuli has been shown to induce neuroplastic effects in the motor and somatosensory system. The objective was to investigate whether the auditory system can be modulated by PAS. Acoustic stimuli (4 kHz) were paired with TMS of the auditory cortex with intervals of either 45 ms (PAS(45 ms)) or 10 ms (PAS(10 ms)). Two-hundred paired stimuli were applied at 0.1 Hz and effects were compared with low frequency repetitive TMS (rTMS) at 0.1 Hz (200 stimuli) and 1 Hz (1000 stimuli) in eleven healthy students. Auditory cortex excitability was measured before and after the interventions by long latency auditory evoked potentials (AEPs) for the tone (4 kHz) used in the pairing, and a control tone (1 kHz) in a within subjects design. Amplitudes of the N1-P2 complex were reduced for the 4 kHz tone after both PAS(45 ms) and PAS(10 ms), but not after the 0.1 Hz and 1 Hz rTMS protocols with more pronounced effects for PAS(45 ms). Similar, but less pronounced effects were observed for the 1 kHz control tone. These findings indicate that paired associative stimulation may induce tonotopically specific and also tone unspecific human auditory cortex plasticity.
Article
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Repeated daily left prefrontal transcranial magnetic stimulation (TMS) was first proposed as a potential treatment for depression in 1993. Multiple studies from researchers around the world since then have repeatedly demonstrated that TMS has antidepressant effects greater than sham treatment, and that these effects are clinically meaningful. A large industry-sponsored trial, published in 2007, resulted in US FDA approval in October 2008. Most recently, a large NIH-sponsored trial, with a more rigorous sham technique, found that a course of treatment (3-5 weeks) was statistically and clinically significant in reducing depression. However, consistently showing statistically and clinically significant antidepressant effects, and gaining regulatory approval, is merely the beginning for this new treatment. As with any new treatment involving a radically different approach, there are many unanswered questions about TMS, and the field is still rapidly evolving. These unanswered questions include the appropriate scalp location, understanding the mechanisms of action, refining the 'dose' (frequency, train, number of stimuli/day and pattern of delivery), understanding whether and how TMS can be combined with medications or talking/exposure therapy, or both, and how to deliver maintenance TMS. This article summarizes the available clinical information, and discusses key areas where more research is needed. TMS reflects a paradigm shift in treating depression. It is a safe, relatively noninvasive, focal brain stimulation treatment that does not involve seizures or implanted wires, and does not have drug-drug interactions or systemic side effects.
Article
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As part of a population-based study in Beaver Dam, Wisconsin, we estimated the 10-year cumulative incidence of tinnitus and its risk factors. Participants (n = 2922, aged 48-92 years) not reporting tinnitus at baseline (1993-1995) were followed for up to ten years. In addition to audiometric testing and anthropometric measures, data on tinnitus, health, and other history were obtained via questionnaire. Potential risk factors were assessed with discrete-time proportional hazards models. The 10-year cumulative incidence of tinnitus was 12.7%. The risk of developing tinnitus was significantly associated with: history of arthritis (hazard ratio (HR = 1.37), history of head injury (HR = 1.76), history of ever smoking (HR = 1.40), and among women, hearing loss (HR = 2.59). Alcohol consumption (HR = 0.63 for > or = 141 grams/week vs. <15 grams/week), age (among women, HR = 0.90 for each five-year increase in age), and among men, obesity (HR = 0.55), were associated with decreased risk. The risk of developing tinnitus was high for older adults, and associated with modifiable health and behavioral factors.
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While controlled trials with SRIs have demonstrated a selective efficacy in obsessive-compulsive disorder (OCD), up to 40-60% of patients do not have a satisfactory outcome. Non-response to treatment in OCD is associated with serious social disability. There are a large number of non-responsive patients, and they are difficult to cluster due to ambiguities in the diagnostic criteria, possibility of subtypes, and a high rate of comorbidity. Moreover, the findings of current studies of so-called 'non-responsive' cases are currently non-generalizable because of the lack of an operational definition of non-response. The result has been that a cumulative body of data on a reasonably homogeneous sample of non-responders has not been developed. The aims of this paper are to clarify some of the obstacles in defining stages of response and levels of non-response and, through a comprehensive analysis, to propose a systematic nosology for this rather common condition. Better characterization of which patients respond and do not respond to various treatments will enable more accurate clustering of patients, and help facilitate multi-site data collection for future research trials.
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The fact that vibration of the skull causes a hearing sensation has been known since the 19th century. This mode of hearing was termed hearing by bone conduction. Although there has been more than a century of research on hearing by bone conduction, its physiology is not completely understood. Lately, new insights into the physiology of hearing by bone conduction have been reported. Knowledge of the physiology, clinical aspects, and limitations of bone conduction sound is important for clinicians dealing with hearing loss and is the purpose of this review. The data were compiled from the published literature in the areas of clinical bone conduction hearing, bone conduction hearing aids, basic research on bone conduction physiology, and recent research on bone conduction hearing from our laboratory. Five factors contributing to bone conduction hearing have been identified: 1) sound radiated into the external ear canal, 2) middle ear ossicle inertia, 3) inertia of the cochlear fluids, 4) compression of the cochlear walls, and 5) pressure transmission from the cerebrospinal fluid. Of these five, inertia of the cochlear fluid seems most important. Bone conduction sound is believed to reflect the true cochlear function; however, certain conditions such as middle ear diseases can affect bone conduction sensitivity, but less than for air conduction. The bone conduction route can also be used for hearing aids; since the bone conduction route is less efficient than the air conduction route, bone conduction hearing aids are primarily used for hearing losses where air conduction hearing aids are contraindicated.
Article
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.
Article
The effective protection provided by arousal of the acoustic reflex against temporary threshold shift (TTS) at 4 kc from exposure to impulse noise was studied by comparing the rate of growth of TTS produced by 2‐min exposures to clicks of successively higher peak levels under two conditions: first, when the clicks were heard alone, and second, when each click was preceded at various intervals from 25 to 150 msec by a 1000‐cps 100‐dB pure tone presented to the contralateral ear. The results imply that the effective attenuation amounts to 1 dB at 25 msec, 5 dB at 62 msec, and 13 dB at 100 msec. Individual differences were large; some of the most slowly responding ears did not show significant protection until the delay reached 150 msec. The practical conclusion reached is that a reflex‐arousal stimulus to be used to protect gun crews should precede firing by 150 msec or more. In regard to theory, the results support the hypothesis that the value of the acoustic impedance of an ear at any instant is an accurate indicator of the protection provided by the middle earmuscles. However, there is also evidence that part of the protection may stem from a change, with reflex arousal, in the peak‐limiting characteristics of the middle ear.
Article
Disrupted neuroplasticity may be an important aspect of the neural basis of schizophrenia. We used event-related brain potentials (ERPs) to assay neuroplasticity after auditory conditioning in chronic schizophrenia patients (SZ) and matched healthy control subjects (HC). Subjects (15 HC, 14 SZ) performed an auditory oddball task during electroencephalogram recording before and after auditory tetanic stimulation (Pre/Post Blocks). Each oddball block consisted of 1000-Hz and 1500-Hz standards and 400-Hz targets. During tetanic conditioning, 1000-Hz tones were presented at 11 Hz for 2.4 min. We analyzed the standard trials, comparing the ERPs evoked by the tetanized stimuli (1000 Hz tones: TS+) and untetanized stimuli (1500 Hz tones: TS-) in the Post Blocks with ERPs from the Pre Blocks (averaged into Baseline ERPs). In Post Block 1 in HC, TS+ tones evoked a negative shift (60-350 msec) at right temporal electrodes relative to Baseline. No pre-/post-tetanus effects were found in SZ. In Post Block 2 in HC, TS+ tones evoked a positive shift (200-300 msec) at bilateral frontal electrodes. In SZ, TS+ tones evoked a positive shift (100-400 msec) at right frontotemporal electrodes. No pre-/post-tetanus effects were found in either subject group for the TS- tones. The right temporal Post Block 1 and 2 effects were correlated in SZ, suggesting a trade-off in the expression of these effects. These results suggest that stimulus-specific auditory neuroplasticity is abnormal in schizophrenia. The electrophysiologic assessment of stimulus-specific plasticity may yield novel targets for drug treatment in schizophrenia.
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
Tinnitus is common; however, few risk factors for tinnitus are known. We examined cross-sectional relations between several potential risk factors and self-reported tinnitus in 14,178 participants in the 1999-2004 National Health and Nutrition Examination Surveys, a nationally representative database. We calculated the prevalence of any and frequent (at least daily) tinnitus in the overall US population and among subgroups. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for multiple potential confounders. Approximately 50 million US adults reported having any tinnitus, and 16 million US adults reported having frequent tinnitus in the past year. The prevalence of frequent tinnitus increased with increasing age, peaking at 14.3% between 60 and 69 years of age. Non-Hispanic whites had higher odds of frequent tinnitus compared with other racial/ethnic groups. Hypertension and former smoking were associated with an increase in odds of frequent tinnitus. Loud leisure-time, firearm, and occupational noise exposure also were associated with increased odds of frequent tinnitus. Among participants who had an audiogram, frequent tinnitus was associated with low-mid frequency (OR 2.37; 95% CI, 1.76-3.21) and high frequency (OR 3.00; 95% CI, 1.78-5.04) hearing impairment. Among participants who were tested for mental health conditions, frequent tinnitus was associated with generalized anxiety disorder (OR 6.07; 95% CI, 2.33-15.78) but not major depressive disorder (OR 1.58; 95% CI, 0.54-4.62). The prevalence of frequent tinnitus is highest among older adults, non-Hispanic whites, former smokers, and adults with hypertension, hearing impairment, loud noise exposure, or generalized anxiety disorder. Prospective studies of risk factors for tinnitus are needed.
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.
Article
The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.
Article
A review of the last 10 years of research on impulse noise reveals certain insights and perspectives on the biological and audiological effects of exposures to impulse noise. First, impulse noise may damage the cochlea by direct mechanical processes. Second, after exposure to impulse noise, hearing may recover in an erratic, nonmonotonic pattern. Third, even though the existing damage-risk criteria evaluate impulse noise in terms of level, duration, and number, often parameters such as temporal pattern, waveform, and rise time are also important in the production of a hearing loss. Fourth, the effects of impulse noise are often inconsistent with the principle of the equal energy hypothesis. Fifth, impulse noise can interact with background continuous noise to produce greater hearing loss than would have been predicted by the simple sum of the individual noises.
In 9 normal volunteers, we studied the safety of rapid-rate transcranial magnetic stimulation (rTMS) applied to different scalp positions at various frequencies and intensities. Pure tone threshold audiometry showed temporary threshold shifts in 3 subjects. In the subject stimulated at the highest intensity, rTMS induced a focal, secondarily generalized seizure despite the absence of definite risk factors for seizures. Rapid-rate TMS did not result in any important changes in the neurological examination findings, cognitive performance, electroencephalogram, electrocardiogram, and hormone levels (prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone). In 10 additional subjects, the electromyographic activity in several contralateral muscles showed that trains of rTMS applied to the motor cortex induced a spread of cortical excitability. The spread of excitability depended on the intensity and frequency of the stimuli and probably constituted an early epileptogenic effect of rTMS. Guidelines for preventing the undesirable side effects of rTMS are offered.
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
Positron emission tomography (PET) during focal repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach to study cortical connectivity in awake humans. However, the noise caused by the discharging magnetic coil might have confounding effects on the rTMS-related cortical activation pattern. In twelve healthy volunteers, 18-fluoro-2-deoxy-D-glucose (18FDG) PET was employed to visualize the functional activation of the primary auditory cortex (PAC) during 2 Hz rTMS of the left primary sensorimotor hand area. Magnetic stimuli (1800) were applied at an intensity of 140% of motor resting threshold during the uptake period of 18FDG. Though all subjects wore earplugs, rTMS-related noise induced a consistent bilateral increase of regional glucose utilization in the PAC (P < 0.05, corrected). Thus, rTMS-related acoustic input needs to be taken into account in combined rTMS/PET studies.
Article
The safety of repetitive transcranial magnetic stimulation (rTMS) has only previously been formally studied in volunteers receiving a single session of stimulation or in a small number of depressed subjects receiving a 2-week treatment course. This study examined safety issues in depressed subjects receiving up to 4 weeks of rTMS. Efficacy results from this study have been previously reported. Eighteen subjects with DSM-IV major depression participated in a 2-week, parallel, double-blind, sham-controlled study of rTMS treatment. Twelve subjects then went on to receive 4 weeks active rTMS in an open follow-up. We examined the effects of rTMS on neuropsychologic function (up to 4 weeks), auditory threshold (up to 6 weeks exposure to rTMS noise), and an electroencephalogram (after 2 weeks). Data were analyzed by repeated measures analysis. There were trends for improvement in neuropsychologic performance, probably due to practice effects. No mean changes in auditory threshold occurred, but two patients showed mild high-frequency hearing loss after several weeks of rTMS. Electroencephalograms in two patients, one of whom had sham stimulation, showed minor abnormality. No significant mean deficits were demonstrated in this cohort. Overall, rTMS for up to 4 weeks is safe, but individual results suggest caution and the need for further investigation of the safety of several weeks of rTMS.
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
The influence of high-frequency repetitive transcranial magnetic stimulation (rTMS) on learning process in mice and on neuronal excitability of the hippocampal tissue obtained from stimulated animals were investigated. While the stimulation with rTMS at higher frequency (15 Hz) improved animals' performance in novel object recognition test (NOR), lower frequency (1 and 8 Hz) impaired the memory. The effect was observed when evaluated immediately after rTMS exposure and declined with time. In parallel to the results of behavioral test, there was a significant enhancement of the synaptic efficiency expressed as of the long-term potentiation (LTP) recorded from hippocampal slices prepared from the animals exposed to 15 Hz rTMS. The stimulation with 1 and 8 Hz had no influence on the magnitude of LTP. Our results demonstrate that rTMS modifies mechanisms involved in memory formation. The effects of rTMS in vivo are preserved and expressed in the hippocampus tested in vitro.
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.
The prevalence of deafness and hearing impairment
  • Davis K Smith
Davis A, Davis K, Smith P. The prevalence of deafness and hearing impairment.
Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil.
  • Zangen A.
  • Roth Y.
  • Voller B.
  • Hallett M.
The prevalence of deafness and hearing impairment
  • A Davis
  • K Davis
  • P Smith
Davis A, Davis K, Smith P. The prevalence of deafness and hearing impairment. In: Graham JM, Baguley DM, editors. Ballantyne's deafness. 4th ed. Chichester, West Sussex: John Wiley & Sons; 2009. p. 6e19.
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 PM, Pascual-Leone A. Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 2009;120: 2008e39.
American Psychiatric Association. Practice guidelines for the treatment of patients with obsessivecompulsive disorder
  • L M Koran
  • G L Hanna
  • E Hollander
  • G Nestadt
  • H B Simpson
Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB, American Psychiatric Association. Practice guidelines for the treatment of patients with obsessivecompulsive disorder. Am J Psychiatry 2007;164:5e53.
Can fear extinction be enhanced? A review of pharmacological and behavioural findings
  • P J Fitzgeral
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Dr Mark Demitrack, Vice President and Chief Medical Officer of Neuronetics
Personal Communication, Dr Mark Demitrack, Vice President and Chief Medical Officer of Neuronetics, Inc., Oct 1, 2007 and Jul 9, 2014.