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Abstract

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.

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... We previously developed controllable pulse parameter TMS (cTMS) to address some of these limitations of conventional TMS devices [95,[98][99][100]. cTMS and related approaches, such as flexTMS [101,102], use switching between one or two oscillators with large capacitors to enable electric field pulses with nearly rectangular shape and some control over the pulse width and, in some cases, the amplitude ratio between the positive and negative pulse phases ( Figure 1C) [95,99,103]. ...
... Coupling various capacitors and inductors has been suggested to bring pulse-shape flexibility [104][105][106][107]. However, these devices are still very limited in their pulse shapes and also cannot generate conventional sinusoidal pulses, such as the traditional monophasic or biphasic waveforms, for comparative studies or to perform already approved clinical procedures [95,98,99,101]. ...
... The inability to alter the pulse amplitude rapidly results from the circuit topologies of conventional devices, which do not allow rapid changes of the voltage of the energy storage capacitor that determines the pulse amplitude. Such limitations also apply to existing TMS devices using various bridge topologies (e.g., Figure 1C), including a restricted set of pulse shapes that can be sustained in repetitive trains as many pulses transfer charge from one capacitor to the other; inability to combine different pulse shapes or amplitudes in a sequence or a train; and suboptimal energy losses and coil heating [95,98,101]. In conclusion, there are multiple technological limitations of existing devices that impede the exploration or adoption of stimulation protocols that could enhance TMS applications. ...
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.
... Standard TMS devices generate sinusoidal pulses with a fixed shape and duration. More advanced devices allow some adjustment of the pulse duration and shape [8][9][10][11]. Such devices have enabled important findings regarding the effect of pulse shape and duration on neural activation thresholds [12], differential neural recruitment in the brain [13][14][15][16][17][18], lasting neuromodulatory effects [19,20], as well as the sensation of scalp stimulation [21]. However, these devices still have a restricted range of the shape (e.g., only sinusoidal or only rectangular), duration (e.g., lacking very brief and very long pulses), and amplitude (e.g., insufficient amplitude for suprathreshold brief or complex pulses) [5,7,22]. ...
... As shown in figure 1(b), each module employs an H-bridge circuit [36], implemented with high-voltage, high-current insulated-gate bipolar transistor (IGBT) switches and appropriate snubber and gate drive circuits, following our approach for prior, simpler TMS device designs [8][9][10]29]. The module's output voltage, Vi, depends on the switches' states and is equal to VCi, 0, or −VCi, where VCi denotes the energy storage capacitor of module i. ...
... States 1-4 actively define the output voltage, which is determined by the commanded transistor states, regardless of the load condition. These states are typically used during all pulse phases except for the last one, allowing the pulse waveform to be accurately controlled [9][10][11]. For states 0 and 5-8, the module output voltage depends on the diode states, which in turn depend on the circuit voltages and currents applied to the diodes. ...
Preprint
Objective: This article presents a novel transcranial magnetic stimulation (TMS) pulse generator with a wide range of pulse shape, amplitude, and width. Approach: Based on a modular multilevel TMS (MM-TMS) topology we had proposed previously, we realized the first such device operating 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 can output pulses including up to 21 voltage levels with a step size of up to 1100 V, allowing relatively flexible generation 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 suprathreshold ultrabrief 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 staircase-approximated 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 in discrete steps by adding or removing modules in series, which enables rapid pulse sequences and paired-pulse protocols with variable pulse shapes and amplitudes. Significance: The MM-TMS device allows unprecedented control of the pulse characteristics which could enable novel protocols and quieter pulses.
... However, the impact of individual pulse shapes on rTMS outcome is unknown because technical limitations prevented systemic variation of pulse shape. Aside from rare exceptions we have only been able to change pulse frequency and patterns [13,14]. ...
... Such customized pulses may be more efficient [16] and could be applied in repetitive trains. In particular, symmetrical, bidirectional pulses, which require little or no capacitor discharging, can be applied at repetition rates of up to 1 kHz [13]. In this study, we made use of the cTMS to test the effect of pulse width and directionality on the sign and temporal evolution of plastic aftereffects. ...
... Many approaches are currently in use to improve the efficacy of rTMS. In this study one of our aims was to elucidate the effects of prolonging the pulse duration of a unidirectional pulse from 40 ms to 120 ms, which is now technically possible with the recently developed cTMS device [13]. A secondary goal was to study the underlying mechanisms of current flow direction by changing the pulse shape from unidirectional to bidirectional while keeping the pulse duration constant. ...
Article
Introduction: Motor evoked potentials (MEP) in response to anteroposterior transcranial (AP) magnetic stimulation (TMS) are sensitive to the TMS pulse shape. We are now able to isolate distinct pulse properties, such as pulse width and directionality and evaluate them individually. Different pulse shapes induce different effects, likely by stimulating different populations of neurons. This implies that not all neurons respond in the same manner to stimulation, possibly, because individual segments of neurons differ in their membrane properties. Objectives: To investigate the effect of different pulse widths and directionalities of TMS on MEP latencies, motor thresholds and plastic aftereffects of rTMS. Methods: Using a controllable pulse stimulator TMS (cTMS), we stimulated fifteen subjects with quasi-unidirectional TMS pulses of different pulse durations (40 μs, 80 μs and 120 μs) and determined thresholds and MEP AP latencies. We then compared the effects of 80 μs quasi-unidirectional pulses to those of 80 μs pulses with different pulse directionality characteristics (0.6 and 1.0 M ratios). We applied 900 pulses of the selected pulse shapes at 1 Hz. Results: The aftereffects of 1 Hz rTMS depended on pulse shape and duration. 40 and 80 μs wide unidirectional pulses induced inhibition, 120 μs wide pulses caused excitation. Bidirectional pulses induced inhibition during the stimulation but had facilitatory aftereffects. Narrower pulse shapes caused longer latencies and higher resting motor thresholds (RMT) as compared to wider pulse shapes. Conclusions: We can tune the aftereffects of rTMS by manipulating pulse width and directionality; this may be due to the different membrane properties of the various neuronal segments such as dendrites. Significance: To date, rTMS frequency has been the main determinant of the plastic aftereffects. However, we showed that pulse width also plays a major role, probably by recruiting novel neuronal targets.
... Thus, neuron models are the key to understanding activation dynamics and studying pulse-shape effects. The temporal shape of pulses was reported to substantially affect efficiency and, thus, coil as well as device heating (Goetz & Peterchev, 2012;Goetz et al., 2013b;Niehaus, Meyer, & Weyh, 2000;Peterchev, Murphy, & Lisanby, 2011), to enable selective activation of certain neuron types or populations (Claus, Murray, Spitzer, & Fl€ ugel, 1990;Corthout et al., 2001;Kammer, Beck, Thielscher, Laubis-Herrmann, & Topka, 2001;Kammer et al., 2007;Ni et al., 2011;Peterchev et al., 2013;Sommer et al., 2014b), and to increase neuromodulation strength compared to standard biphasic pulses in repetitive protocols (Antal et al., 2002;Arai et al., 2005Arai et al., , 2007Goetz et al., 2016b;Hannah, Ciocca, Sommer, Hammond, & Rothwell, 2014;Sommer et al., 2014a;Sommer, Lang, Tergau, & Paulus, 2002;Sommer et al., 2013). Finally, neuron models also explain and predict directionality effects of TMS, i.e. why the orientation of the coil affects the threshold and allows activation of different neuron populations (Goetz et al., 2016b;Niehaus et al., 2000). ...
... Recent developments have achieved overcoming the pulse-shape limitation and allow for adjusting the shape during operation. Several refinements of a TMS technology that enables the configuration of pulse parameters (cTMS) have been demonstrated and are available commercially (Figure 6(c)) (Peterchev, D'Ostilio, Rothwell, & Murphy, 2014;Peterchev, Jalinous, & Lisanby, 2008;Peterchev et al., 2011). cTMS splits a pulse into few near-rectangular voltage segments, which can be adjusted in amplitude and duration. ...
... The simplest model in TMS research is the leaky integrate-and-fire neuron (Bostock, 1983;Corthout et al., 2001;Lapicque, 1907;Peterchev et al., 2011). This model describes the excitable neural membrane as a leaking electrical capacitor, i.e. a parallel connection of a capacitor C, which can be charged up by stimulation, and a resistor R, which discharges the capacitor with a time-constant of s ¼ RC. ...
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.
... Specifically, even though the dominant frequency content of ultrabrief single-period sinusoidal pulses is in the ultrasound range, the spectrum contains several strong subharmonic side bands. In contrast, rectangular electric field pulses are more energy efficient and require lower voltage [5,9,10]. Importantly, they shift the energy to higher acoustic frequencies than a conventional sinusoidal pulse with matched duration, because of the high-frequency harmonics present in the rectangular pulse. ...
... We used a controllable pulse parameter TMS (cTMS) device developed in our lab [9] to generate ultrabrief (45 μs pulse period, ~ 23 μs middle phase width), rectangular electric field pulses, shown in Fig. 2. The comparison pulses were of conventional duration (300 μs pulse period). The amplitudes of the long and short pulses are scaled according to the strength duration relationship of cortical neurons, so that both pulse types have matched neurostimulation strength [6,8]. ...
... The peak voltage of the ultrabrief pulses is ~ 1 kV, corresponding to the cTMS device limit for symmetric pulses. Conventional length (300 μs) and ultrabrief (45 μs) pulses generated by a cTMS device [9] with conventional Magstim 90 mm circular coil (A, B) and a prototype qTMS coil (C, D). Coils pictured on right side. ...
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.
... To address these technological limitations we developed a controllable pulse parameter TMS (cTMS) device that enables the efficient generation of pulses with various shapes (45,46). In the present study, we used a cTMS device and a standard rTMS device to stimulate motor cortex to compare the average effects on motor evoked potentials (MEPs) amplitude of 1 Hz trains of several novel types of pulse shapes with the standard biphasic sinusoidal pulse. ...
... Note that all these pulses correspond to biphasic magnetic pulses; the electric field phase amplitudes are manipulated by changing the magnetic field rise and fall times (46). Phases with positive polarity in Figure 2 correspond to induced current flowing in the PA direction in the brain under the center of the figure-of-eight coil, whereas phases with negative polarity correspond to induced current in the AP direction. ...
... The reason for that limitation is the high power requirement and heat dissipation associated with the conventional circuit for generating the monophasic pulse (42). The novel approach taken in this study was to generate biphasic magnetic pulses with different rise and fall times, resulting in differing degrees of bidirectionality (45,46). The more unidirectional of these pulses (RU-N and RU-R) have electric fields similar to conventional monophasic pulses, but can be generated at higher repetition rates with the existing cTMS device. ...
... 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). ...
... Addressing this need, we have developed a family of TMS devices with controllable pulse parameters (cTMS) including low repetition rate TMS (cTMS1) [13] and high rate rTMS (cTMS2) [14]. cTMS1 uses a large energy storage capacitor and a single insulated gate bipolar transistor (IGBT) switch to enable pulse width control. ...
... cTMS2 deploys two capacitors and two IGBTs to extend the controllable coil voltage levels from one to two, and to provide efficient high rate rTMS operation; it requires an active snubbing circuit to suppress ringing at the end of each pulse. With these devices we demonstrated adjustment of the number, polarity, duration, and amplitude of the electric field pulse phases; reduction of power consumption and coil heating; and motor cortex stimulation in non-human primates and humans [13][14][15]. Another device that aims to improve the adjustability of the pulse shape, flexTMS, uses four IGBT switches, forming an H-bridge, to connect the coil to a single energy storage capacitor [17]. ...
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.
... Commercially available TMS devices induce damped cosine electric field pulses, with non-existent or very limited control over the pulse shape parameters [1]- [3]. 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 [3]- [6]. Addressing this need, we have developed a family of TMS devices with controllable pulse parameters (cTMS) for single-pulse/lowfrequency TMS [5] and high-frequency repetitive TMS [6]. ...
... 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 [3]- [6]. Addressing this need, we have developed a family of TMS devices with controllable pulse parameters (cTMS) for single-pulse/lowfrequency TMS [5] and high-frequency repetitive TMS [6]. cTMS devices enable adjustment of the number, polarity, duration, and amplitude of the electric field pulse phases, while reducing power consumption and coil heating. ...
... In this paper we extend that line of work by introducing and analyzing a new cTMS circuit topology (full-bridge) capable of high-frequency repetitive TMS. The full-bridge cTMS topology offers more flexibility of pulse shape adjustment and potentially some implementation advantages over the half-bridge topology that we have previously implemented and characterized experimentally [6]. We compare the two topologies through theoretical analysis and simulations, and discuss design considerations, such as limitations on the pulse parameter adjustment ranges and tradeoffsi n the coil design. ...
Conference Paper
We compare half-bridge and full-bridge circuit topologies for controllable pulse parameter transcranial magnetic stimulation (cTMS) devices. The full bridge can generate two more distinct coil voltage levels for enhanced pulse shaping, does not need an active snubber circuit, and requires lower semiconductor switch voltage ratings, at the cost of necessitating four semiconductor switches and associated drivers compared to two in the half bridge. In cTMS devices it may be beneficial to use coils with higher number of turns and, hence, higher inductance than that optimal in conventional TMS, since this reduces the required capacitance, stored energy, coil current, and, potentially, conduction losses and heating. However, increasing the number of coil turns raises the required capacitor voltage which presents practical limits on the number of turns, especially for very brief pulses.
... To change the pulse polarity, the orientation of the coil must be changed mechanically (because the circuit is not symmetric with respect to the coil). 4) By using a half-bridge inverter structure, monophasic and biphasic near-rectangular stimuli can be generated (cTMS2) [5]. As demonstrated in Table II, the use of two asymmetric structures in the DC link forces the stimulus to have a positive phase with a higher voltage but lower width and a negative phase with a lower voltage and a higher width. ...
... To investigate the energy loss of the pTMS device in comparison with that of other structures, as an indicator of energy efficiency, the energy that is not recovered back on the CES at the end of the stimulus (Δ ) is calculated as in [5]: Table II. The introduced pTMS device operates at a high switching frequency and so its loss is somewhat higher than others. ...
Article
Full-text available
Objective: A transcranial magnetic stimulation system with programmable stimulus pulses and patterns is presented. The stimulus pulses of the implemented system expand beyond conventional damped cosine or near-rectangular pulses and approach an arbitrary waveform. Methods: The desired stimulus waveform shape is defined as a reference signal. This signal controls the semiconductor switches of an H-bridge inverter to generate a high-power imitation of the reference. The design uses a new paradigm for TMS, applying pulse-width modulation with a non-resonant, high-frequency switching architecture to synthesize waveforms that leverages the low-pass filtering properties of neuronal cells. The modulation technique enables control of the waveform, frequency, pattern, and intensity of the stimulus. Results: A system prototype was developed to demonstrate the technique. The experimental measurements demonstrate that the system is capable of generating stimuli up to 4 kHz with peak voltage and current values of ±1000 V and ±3600 A, respectively. The maximum transferred energy measured in the experimental validation was 100.4 Joules. To characterize repetitive TMS modalities, the efficiency of generating consecutive pulse triplets and quadruplets with interstimulus intervals of 1 ms was tested and verified. Conclusion: The implemented TMS device can generate consecutive rectangular pulses with a predetermined time interval, widths and polarities, enables the synthesis of a wide range of magnetic stimuli. Significance: New waveforms promise functional advantages over the waveforms generated by current-generation TMS systems for clinical neuroscience research.
... As opposed to fully discharging the energy storage capacitor, stimulation circuit architectures that truncate the flow of current in the coil have been developed for use in controllable pulse width transcranial magnetic stimulation (cTMS). This current truncation is achieved using an insulated gate bipolar transistor (IGBT) to enable pulse width control [20,21,22,23]. Modeling suggests continuing the flow of current after it has reached a maximum only results in resistive losses in the coil and coil heating, without a substantive increase in the neural response [20]. ...
... The results described herein support the hypothesis that truncating the current flowing through a magnetic stimulating coil can effectively evoke neuromuscular responses via the PNS with reduced energy consumption compared with nontruncated stimuli. In adapting this cTMS approach towards use in a smaller implantable PNS application, we also generate a current waveform that truncates more quickly than in many cTMS systems [20,21,22,23]. Moreover, the heat developed in the coils is also reduced with stimulus truncation. ...
Article
Current truncating circuit designs used in some controllable pulse width transcranial magnetic stimulation systems can be adapted for use with the peripheral nervous system. Such a scaled-down stimulator produces neuromuscular activation using less stimulus energy than described in previous reports of sciatic nerve stimulation. To evaluate the energy reductions possible with current truncation, we performed six in vivo experiments in rats where the magnetic stimulating coil abutted the sciatic nerve. We used electromyographic data to quantify neuromuscular response, with a criterion level of 20%-of-maximum to indicate a useful level of neuromuscular activation. The energy required to evoke this criterion response from muscles innervated by the sciatic nerve was reduced by approximately 34% from 10.7J with a stimulus waveform lasting 300 ${\mu }\text{s}$ to 7.1J with a waveform lasting 50 ${\mu }\text{s}$ . In water, the 300 ${\mu }\text{s}$ pulse heated the coil by 0.30°C whereas the 50 ${\mu }\text{s}$ pulse heated the coil by 0.15°C. Truncated-waveform magnetic stimulation systems can be used in basic research and clinical applications not requiring rapidly pulsed stimuli. An example of such a clinical application is left vagus nerve stimulation, a treatment that is reported to reduce epileptic partial-onset seizures.
... In TMS, the current pulse to the TMS coil is often provided by rapidly discharging a capacitor through the coil [20,29]. The fundamental time constant τ d for this discharge is given by t p = LC 2 d where L is the inductance of the coil and C is the capacitance. ...
... This time-constant gives the oscillation period if the capacitor-coil system were left to oscillate. In practice the discharge is usually terminated before a full period occurs [29], capturing much of the energy that has been transferred to current in the coil in another capacitor. For human TMS, the time-constant is often around 0.5ms. ...
Article
Introduction. Transcranial magnetic stimulation (TMS) is used for treating neurological disorders. Rapid pulses of magnetic field are delivered via a high-current coil situated over the scalp and induce an electric field in the brain. There has been limited fundamental scientific research on TMS and to progress it would be ideal to mimic the electric field of human TMS with mice. Animal models provide good mechanistic insight, but their use is hindered by lack of stimulating coils comparable in focus and intensity with human stimulation. Methods. We outline the engineering challenges in producing appropriate coils. It is unclear what should be optimized in the design of a mouse coil. We model the electric field, heat generation and ring-down time for cylindrical coils and use results to select a coil design consisting of 70 turns of 0.4 mm diameter copper wire wrapped around a 5 mm diameter soft ferrite core. Results and Discussion. While the magnetic flux density scales as the reciprocal of length-scale, the electric field does not scale with length, meaning that a large current is required to mimic the electric field of humans. To maximize electric field, one must minimize the coil's inductance resulting in reduced ring-down time for the coil and significant heating. A ferrite core allows ring-down time to remain high and reduces heating. Our coil gave 180 mT at 30 V supply, with a temperature increase of 5°C after 1200 pulses at 5 Hz. The B-field below the core has a full-width-at-half-maximum of 6 mm, similar in size to a mouse brain. Conclusions. We have produced a mouse coil that offers increased B-field and reduced heating. There is considerable scope for improving electric field, but further physical analysis may lead to field strength more similar to that obtained in human TMS.
... As well, some commercial TMS devices allow adjustment, albeit limited, of the pulse width [26,27]. Finally, we have developed a family of TMS devices with controllable pulse param-eters (cTMS) that allow adjustment of the pulse width over a substantial range, potentially allowing optimization of this parameter [28][29][30]. ...
... It is possible that the pulse characteristics such as pulse width affect the perception of TMS in different ways for single pulses and for pulse trains. In future studies, the pulse characteristics of repetitive TMS pulse trains could be modified using cTMS devices that allow high-frequency trains [29,30]. Moreover, this study did not explore the differences in sensation between conventional sinusoidal pulses and cTMS near-rectangular 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.
... A variety of different TMS pulse forms has recently been suggested [55], [57], [58]. We will model a simple monophasic (monopolar) TMS pulse. ...
... Table SIIb (given in the Supplement) reports the ratio of two peak pulse values (analytical versus numerical) for the same 40 datasets, respectively. Along with the pulse rise time of 0.1 ms, we also present the result for a smaller value of 0.01 ms, which can be used as an excitation in TMS coils too [57], [58]. ...
Article
Goals: Transcranial magnetic stimulation (TMS) is increasingly used as a diagnostic and therapeutic tool for numerous neuropsychiatric disorders. The use of TMS might cause whole-body exposure to undesired induced currents in patients and TMS operators. The aim of the present study is to test and justify a simple analytical model known previously, which may be helpful as an upper estimate of eddy current density at a particular distant observation point for any body composition and any coil setup. Methods: We compare the analytical solution with comprehensive adaptive mesh refinement-based FEM simulations of a detailed full-body human model, two coil types, five coil positions, about 100,000 observation points, and two distinct pulse rise times, thus providing a representative number of different data sets for comparison, while also using other numerical data. Results: Our simulations reveal that, after a certain modification, the analytical model provides an upper estimate for the eddy current density at any location within the body. In particular, it overestimates the peak eddy currents at distant locations from a TMS coil by a factor of 10 on average. Conclusion: The simple analytical model tested in the present study may be valuable as a rapid method to safely estimate levels of TMS currents at different locations within a human body. Significance: At present, safe limits of general exposure to TMS electric and magnetic fields are an open subject, including fetal exposure for pregnant women.
... This technology does not allow the generation of significantly briefer pulses required to excite acoustic emission at higher frequencies. Therefore, we used a custom TMS device based on insulated gate bipolar transistors (IGBTs) [Peterchev 2011] to generate a range of biphasic current pulses with main oscillatory period from 45 to 470 μs. The current pulse waveform is nearly triangular, corresponding to an approximately rectangular electric field [Peterchev 2011]. ...
... Therefore, we used a custom TMS device based on insulated gate bipolar transistors (IGBTs) [Peterchev 2011] to generate a range of biphasic current pulses with main oscillatory period from 45 to 470 μs. The current pulse waveform is nearly triangular, corresponding to an approximately rectangular electric field [Peterchev 2011]. For these pulses, the TMS device allowed peak coil voltages up to 1400 V, corresponding to peak coil currents of 1504 A (for 45-μs pulse duration) and 9120 A (for 470-μs pulse duration). ...
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.
... The RMSE constraint had a larger influence on the reduction of coil 6 heating compared to the pulse duration ( Figures 2B): relaxing the RMSE constraint (higher RMSE) reduced the 7 heating more than increasing the non-zero pulse waveform duration. This was mostly due to higher RMSE resulting 8 in a current waveform that had a main phase with significantly shorter duration and lower amplitude compared to 9 the original TMS pulse, and shorter TMS pulses are known to require less energy and produce less heating 10 [36,47,64,65]. For long pulse durations, further increasing the duration had a diminishing return on the reduction of 11 heating, e.g., increasing pulse duration from 4 ms to 6 ms resulted in a smaller change of coil heating compared to 12 that for pulse duration increased from 2 ms to 4 ms. ...
Preprint
Objective. Transcranial magnetic stimulation (TMS) with monophasic pulses achieves greater changes in neuronal excitability but requires higher energy and generates more coil heating than TMS with biphasic pulses, and this limits the use of monophasic pulses in rapid-rate protocols. We sought to design a stimulation waveform that retains the characteristics of monophasic TMS but significantly reduces coil heating, thereby enabling higher pulse rates and increased neuromodulation effectiveness. Approach. A two-step optimization method was developed that uses the temporal relationship between the electric field (E-field) and coil current waveforms. The optimization step reduced the ohmic losses of the coil current and constrained the error of the E-field waveform compared to a template monophasic TMS pulse, with pulse duration as a second constraint. The second, amplitude adjustment step scaled the candidate waveforms based on simulated neural activation to account for differences in stimulation thresholds. The optimized waveforms were implemented to validate the changes in coil heating. Main results. Depending on the pulse duration and E-field matching constraints, the optimized waveforms produced 12% to 75% less heating than the original monophasic pulse. The results were robust across a range of neural models. The changes in the measured ohmic losses of the optimized pulses compared to the original pulse agreed with numeric predictions. Significance. The first step of the optimization approach was model-free and exhibited robust performance by avoiding the highly non-linear behavior of neural responses, while neural simulations were only run once for amplitude scaling in the second step. This significantly reduced computational cost compared to iterative methods using large populations of candidate solutions and reduced the sensitivity to choice of neural model. The reduced coil heating and power losses of the optimized pulses can enable rapid-rate monophasic TMS protocols.
... For example, Reilly et al. provided a theoretical basis that explained why monophasic pulses might be more effective at neuromodulation than the biphasic pulses typically used in TMS [21]. Peterchev et al. demonstrated a TMS power supply circuit that could apply currents with rapid rise times to TMS coils with slow fall times, effectively generating primarily monophasic electric pulses [22]. ...
Article
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Opening the blood brain barrier (BBB) under imaging guidance may be useful for the treatment of many brain disorders. Rapidly applied magnetic fields have the potential to generate electric fields in brain tissue that, if properly timed, may enable safe and effective BBB opening. By tuning magnetic pulses generated by a novel electropermanent magnet (EPM) array, we demonstrate the opening of tight junctions in a BBB model culture in vitro, and show that induced monophasic electrical pulses are more effective than biphasic ones. We confirmed, with in vivo contrast-enhanced MRI, that the BBB can be opened with monophasic pulses. As electropermanent magnets have demonstrated efficacy at tuning B0 fields for magnetic resonance imaging studies, our results suggest the possibility of implementing an EPM-based hybrid theragnostic device that could both image the brain and enhance drug transport across the BBB in a single sitting.
... Biphasic TMS pulses were generated by sequentially turning ON and OFF the two IGBT units, allowing for energy transfer among C1, L, and C2. The highvoltage circuit topology is similar to Ref. [53] except that the active snubber circuits across L were eliminated because we observed only minor oscillation following each pulse. Notably, a stray-inductance minimizing the PCB-based snubber circuit and improved laminated bus bars were recently described in a multilevel TMS device that delivered wide output ranges and ultra-brief pulses [54]. ...
Article
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Background Theta burst stimulation (TBS) is an efficient noninvasive neuromodulation paradigm that has been widely adopted, clinically. However, the efficacy of TBS treatment remains similarly modest as conventional 10 Hz repetitive transcranial magnetic stimulation (rTMS). Objective/hypothesis To develop a new TBS paradigm that enhances the effects of TMS administration while maintaining high time-efficiency. Methods We describe here a new TMS paradigm, named High-Density Theta Burst Stimulation (hdTBS). This paradigm delivers up to 6 pulses per burst, as opposed to only 3 in conventional TBS, while maintaining the inter-burst interval of 200 ms (or 5 Hz) – a critical parameter in inducing long-term potentiation. This paradigm was implemented on a TMS stimulator developed in-house; its physiological effects were assessed in the motor cortex of awake rats using a rodent specific focal TMS coil. Microwire electrodes were implanted into each rat's limb muscles to longitudinally record motor-evoked potential (MEP). Four different TBS paradigms (3, 4, 5 or 6 pulses per burst, 200 s per session) were tested; MEP signals were recorded immediately before (baseline) and up to 35 min post each TBS session. Results We developed a stimulator based on a printed-circuit board strategy. The stimulator was able to deliver stable outputs of up to 6 pulses per burst. Animal experiments (n = 15) revealed significantly different aftereffects induced by the four TBS paradigms (Friedman test, p = 0.018). Post hoc analysis further revealed that, in comparison to conventional 3-pulse TBS, 5- and 6-pulse TBS enhanced the aftereffects of MEP signals by 56% and 92%, respectively, while maintaining identical time efficiency. Conclusion(s) A new stimulation paradigm is proposed, implemented and tested in the motor cortex of awake rats using a focal TMS coil developed in the lab. We observed enhanced aftereffects as assessed by MEP, with no obvious adverse effects, suggesting the translational potentials of this paradigm.
... The effects of key rTMS parameters, i.e., stimulation frequency, intensity, and number of pulses and sessions, on plastic aftereffects have been closely investigated (Rossini et al., 2015). However, there are few studies on the impact of pulse duration on rTMS outcome due to the scarcity of devices with adjustable pulse durations (Peterchev et al., 2011). ...
Article
Full-text available
Introduction: High frequency repetitive transcranial magnetic stimulation applied to the motor cortex causes an increase in the amplitude of motor evoked potentials (MEPs) that persists after stimulation. Here, we focus on the aftereffects generated by high frequency controllable pulse TMS (cTMS) with different directions, intensities, and pulse durations. Objectives: To investigate the influence of pulse duration, direction, and amplitude in correlation to induced depolarization on the excitatory plastic aftereffects of 5 Hz repetitive transcranial magnetic stimulation (rTMS) using bidirectional cTMS pulses. Methods: We stimulated the hand motor cortex with 5 Hz rTMS applying 1,200 bidirectional pulses with the main component durations of 80, 100, and 120 μs using a controllable pulse stimulator TMS (cTMS). Fourteen healthy subjects were investigated in nine sessions with 80% resting motor threshold (RMT) for posterior-anterior (PA) and 80 and 90% RMT anterior-posterior (AP) induced current direction. We used a model approximating neuronal membranes as a linear first order low-pass filter to estimate the strength–duration time constant and to simulate the membrane polarization produced by each waveform. Results: PA and AP 5 Hz rTMS at 80% RMT produced no significant excitation. An exploratory analysis indicated that 90% RMT AP stimulation with 100 and 120 μs pulses but not 80 μs pulses led to significant excitation. We found a positive correlation between the plastic outcome of each session and the simulated peak neural membrane depolarization for time constants >100 μs. This correlation was strongest for neural elements that are depolarized by the main phase of the AP pulse, suggesting the effects were dependent on pulse direction. Conclusions: Among the tested conditions, only 5 Hz rTMS with higher intensity and wider pulses appeared to produce excitatory aftereffects. This correlated with the greater depolarization of neural elements with time constants slower than the directly activated neural elements responsible for producing the motor output (e.g., somatic or dendritic membrane). Significance: Higher intensities and wider pulses seem to be more efficient in inducing excitation. If confirmed, this observation could lead to better results in future clinical studies performed with wider pulses.
... Repetitive TMS protocols, particularly monophasic paradigms, have always been associated with an energy recovery challenge [1]. Recently, the use of state-of-the-art power electronic instruments has permitted more control over the waveform parameters [2] [3] [4]. A novel technique utilizing pulse width modulation (PWM), called programmable TMS or pTMS [5], enables the imitation of a wide range of arbitrary pulses. ...
Preprint
Full-text available
Objective: We developed a novel transcranial magnetic stimulation (TMS) device to generate flexible stimuli and patterns. The system synthesizes digital equivalents of analog waveforms, relying on the filtering properties of the nervous system. Here, we test the hypothesis that the novel pulses can mimic the effect of conventional pulses on the cortex. Approach: A second-generation programmable TMS (pTMS2) stimulator with magnetic pulse shaping capabilities using pulse-width modulation (PWM) was tested. A computational and an in-human study on twelve healthy participants compared the neuronal effects of conventional and modulation-based stimuli. Main results: Both the computational modeling and the in-human stimulation showed that the PWM-based system can synthesize pulses to effectively stimulate the human brain, equivalent to conventional stimulators. The comparison includes motor threshold, MEP latency and input-output curve measurements. Significance: PWM stimuli can fundamentally imitate the effect of conventional magnetic stimuli while adding considerable flexibility to TMS systems, enabling the generation of highly configurable TMS protocols.
... The operation of the mTMS device is based on forced current feed through the transducer coils, which is achieved by manipulating the electrical topologies of the coil-specific bridge circuits; see [16,18,19,21,22]. Depending on the states of the IGBTs, a bridge circuit either connects its respective pulse capacitor in series with the coil connected to the channel ( Fig. 2A,C), resulting in a damped oscillator circuit, or cuts the capacitor completely out of the circuit while also shortcircuiting the coil's ends (Fig. 2B). ...
Article
Full-text available
Background Transcranial magnetic stimulation (TMS) allows non-invasive stimulation of the cortex. In multi-locus TMS (mTMS), the stimulating electric field (E-field) is controlled electronically without coil movement by adjusting currents in the coils of a transducer. Objective To develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region. Methods We designed and manufactured a planar 5-coil mTMS transducer to allow controlling the maximum of the induced E-field within a cortical region approximately 30 mm in diameter. We developed electronics with a design consisting of independently controlled H-bridge circuits to drive up to six TMS coils. To control the hardware, we programmed software that runs on a field-programmable gate array and a computer. To induce the desired E-field in the cortex, we developed an optimization method to calculate the currents needed in the coils. We characterized the mTMS system and conducted a proof-of-concept motor-mapping experiment on a healthy volunteer. In the motor mapping, we kept the transducer placement fixed while electronically shifting the E-field maximum on the precentral gyrus and measuring electromyography from the contralateral hand. Results The transducer consists of an oval coil, two figure-of-eight coils, and two four-leaf-clover coils stacked on top of each other. The technical characterization indicated that the mTMS system performs as designed. The measured motor evoked potential amplitudes varied consistently as a function of the location of the E-field maximum. Conclusion The developed mTMS system enables electronically targeted brain stimulation within a cortical region.
... As conventional magnetic brain stimulators have relatively fixed pulse characteristics (other than amplitude), it has not been previously possible to assess this variable with TMS. However, technological advances have enabled development of stimulators with controllable pulse parameters (103,104), and these have been used to estimate strength-duration time constants of the neuronal circuits activated by TMS by modifying pulse-duration (105). In an attempt to further characterize the intracortical circuits activated by different current directions, D'Ostilio et al. (106) used this approach to assess strength-duration time constants for PA and AP stimulation. ...
Article
Objectives: The corticospinal volley produced by application of transcranial magnetic stimulation (TMS) over primary motor cortex consists of a number of waves generated by trans‐synaptic input from interneuronal circuits. These indirect (I)‐waves mediate the sensitivity of TMS to cortical plasticity and intracortical excitability and can be assessed by altering the direction of cortical current induced by TMS. While this methodological approach has been conventionally viewed as preferentially recruiting early or late I‐wave inputs from a given populations of neurons, growing evidence suggests recruitment of different neuronal populations, and this would strongly influence interpretation and application of these measures. The aim of this review is therefore to consider the physiological, functional, and clinical evidence for the independence of the neuronal circuits activated by different current directions. Materials and Methods To provide the relevant context, we begin with an overview of TMS methodology, focusing on the different techniques used to quantify I‐waves. We then comprehensively review the literature that has used variations in coil orientation to investigate the I‐wave circuits, grouping studies based on the neurophysiological, functional, and clinical relevance of their outcomes. Results Review of the existing literature reveals significant evidence supporting the idea that varying current direction can recruit different neuronal populations having unique functionally and clinically relevant characteristics. Conclusions Further research providing greater characterization of the I‐wave circuits activated with different current directions is required. This will facilitate the development of interventions that are able to modulate specific intracortical circuits, which will be an important application of TMS.
... For example, two half-sine pulses with a lag of ¼ of a cycle will cover only one quarter of the 360° phase space, while similar pulses truncated even earlier in their cycle, before the current reaches zero, may lead to rfTMS covering even smaller orientational portions. Such pulses can be produced with approaches such as controllable TMS (33). As another option, operation of two half-sine pulses by the two coils, which have orthogonal orientations or any other relative angle, consecutively with no temporal overlap, will induce field only in these two orientations. ...
Article
Full-text available
Background Transcranial magnetic stimulation (TMS) is a rapidly expanding technology utilized in research and neuropsychiatric treatments. Yet, conventional TMS configurations affect primarily neurons that are aligned parallel to the induced electric field by a fixed coil, making the activation orientation-specific. A novel method termed rotational field TMS (rfTMS), where two orthogonal coils are operated with a 90° phase shift, produces rotation of the electric field vector over almost a complete cycle, and may stimulate larger portion of the neuronal population within a given brain area. Objective To compare the physiological effects of rfTMS and conventional unidirectional TMS (udTMS) in the motor cortex. Methods Hand and leg resting motor thresholds (rMT), and motor evoked potential (MEP) amplitudes and latencies (at 120% of rMT), were measured using a dual-coil array based on the H7-coil, in 8 healthy volunteers following stimulation at different orientations of either udTMS or rfTMS. Results For both target areas rfTMS produced significantly lower rMTs and much higher MEPs than those induced by udTMS, for comparable induced electric field amplitude. Both hand and leg rMTs were orientation-dependent. Conclusions rfTMS induces stronger physiologic effects in targeted brain regions at significantly lower intensities. Importantly, given the activation of a much larger population of neurons within a certain brain area, repeated application of rfTMS may induce different neuroplastic effects in neural networks, opening novel research and clinical opportunities.
... The recent development of controllable pulse parameter TMS (cTMS) devices allows near rectangular electric field pulses to be induced while reducing power consumption and coil overheating [30]. cTMS permits controllability over the width, polarity, number, frequency, and duration of pulses that may permit neuronal populations with distinct strength-duration characteristics to be selectively activated [31]. ...
Chapter
Transcranial magnetic stimulation (TMS) is a non-invasive method for neuromodulation which involves the application of brief magnetic pulses to the cortex to induce intracortical currents below the area of stimulation. The manipulation of stimulation parameters can alter the spatial and temporal patterns of cortical activation. Combining TMS with neurophysiological and neuroimaging modalities, such as electroencephalography (EEG) and stereotactic neuronavigation, respectively, can allow for a cause-and-effect approach to study cortical processes in vivo with very good spatial and excellent temporal precision. Investigation of cortical network properties may allow for the development of predictors and biomarkers of the pathophysiology of brain disorders, which can help bridge the gap between basic research and clinical applications. Already, therapeutic TMS paradigms are being used to treat medication-resistant depression and can potentially be used to ameliorate symptoms in other psychiatric or neurological disorders. Furthermore, navigated TMS procedures are increasingly being used for preoperative functional mapping of motor and language regions and can improve postoperative outcomes. Thus, TMS carries tremendous promise to assess brain properties in healthy and diseased states and can be used to optimize the efficacy of brain stimulation treatments in clinical populations.
... While there is appreciable device-to-device output variability of focality and magnitude of stimulation via TMS, the overall pulse width, and pulse shape (monophasic and biphasic) are relatively consistent across devices. Experimental devices with variable pulse width and shape are emerging, but thus to date are not widely implemented (Peterchev et al., 2011). In the most common FIGURE 1 | Representative transcranial magnetic stimulation (TMS) motor cortex activation. ...
Article
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Epilepsy is associated with numerous neurodevelopmental disorders. Transcranial magnetic stimulation (TMS) of the motor cortex coupled with electromyography (EMG) enables biomarkers that provide measures of cortical excitation and inhibition that are particularly relevant to epilepsy and related disorders. The motor threshold (MT), cortical silent period (CSP), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) are among TMS-derived metrics that are modulated by antiepileptic drugs. TMS may have a practical role in optimization of antiepileptic medication regimens, as studies demonstrate dose-dependent relationships between TMS metrics and acute medication administration. A close association between seizure freedom and normalization of cortical excitability with long-term antiepileptic drug use highlights a plausible utility of TMS in measures of anti-epileptic drug efficacy. Finally, TMS-derived biomarkers distinguish patients with various epilepsies from healthy controls and thus may enable development of disorder-specific biomarkers and therapies both within and outside of the epilepsy realm.
... Noninvasive stimulation of the primary motor cortex is used for the diagnosis and localization of motor lesions [13]. Furthermore, the primary motor cortex is a preferred model for studying the neurophysiology, biophysics of brain stimulation, and development of novel technology [14][15][16]. According to safety guidelines of repetitive TMS, the motor threshold is the reference of individual dosage also for other brain targets that are silent [17]. ...
Preprint
Full-text available
Motor evoked potentials (MEPs) are used for biomarkers or dose individualization in transcranial stimulation. We aimed to develop a statistical model that can generate long sequences of individualized MEP amplitude data with the experimentally observed properties. The MEP model includes three sources of trial-to-trial variability to mimic excitability fluctuations, variability in the neural and muscular pathways, and physiological and measurement noise. It also generates virtual human subject data from statistics of population variability. All parameters are extracted as statistical distributions from experimental data from the literature. The model exhibits previously described features, such as stimulus-intensity-dependent MEP amplitude distributions, including bimodal ones. The model can generate long sequences of test data for individual subjects with specified parameters or for subjects from a virtual population. The presented MEP model is the most detailed to date and can be used for the development and implementation of dosing and biomarker estimation algorithms for transcranial stimulation.
... Additionally, MEP latencies of AP-directed stimuli were shown to vary with pulse duration. Direct comparison of the present results with commercially-available devices is difficult since most permit little or no control over pulse width Rothkegel et al., 2010) and exhibit a sinusoidal pulse shape which differs from the more rectangular pulses delivered via the cTMS device (Peterchev et al., 2011). However, the frequently used Magstim 200 2 stimulator (The Magstim Company Limited, UK) has a pulse width of 82 ls (Rothkegel et al., 2010), which lies in the upper range of pulse widths examined in the present study (30-120 ls). ...
Article
OBJECTIVE: To compare the strength–duration (S–D) time constants of motor cortex structures activated by current pulses oriented posterior–anterior (PA) or anterior–posterior (AP) across the central sulcus. METHODS: Motor threshold and input–output curve, along with motor evoked potential (MEP) latencies, of first dorsal interosseus were determined at pulse widths of 30, 60, and 120 μs using a controllable pulse parameter (cTMS) device, with the coil oriented PA or AP. These were used to estimate the S–D time constant and we compared with data for responses evoked by cTMS of the ulnar nerve at the elbow. RESULTS: The S–D time constant with PA was shorter than for AP stimulation (230.9 ± 97.2 vs. 294.2 ± 90.9 μs; p < 0.001). These values were similar to those calculated after stimulation of ulnar nerve (197 ± 47 μs). MEP latencies to AP, but not PA stimulation were affected by pulse width, showing longer latencies following short duration stimuli. CONCLUSIONS: PA and AP stimuli appear to activate the axons of neurons with different time constants. Short duration AP pulses are more selective than longer pulses in recruiting longer latency corticospinal output. Significance More selective stimulation of neural elements may be achieved by manipulating pulse width and orientation.
... A new device has only recently enabled us to explore this parameter in the central nervous system. The device, named "controllable pulse parameter TMS" (cTMS), can manipulate the pulse shape, including the PW [13,14]. The notion of "the wider, the stronger" has been confirmed in the central nervous system by measuring the motor threshold for singlepulse TMS [15,16]. ...
Article
Background: Paired-pulse protocols have played a pivotal role in neuroscience research using transcranial magnetic stimulation (TMS). Stimulus parameters have been optimized over the years. More recently, pulse width (PW) has been introduced to this field as a new parameter, which may further fine-tune paired-pulse protocols. The relationship between the PW and effectiveness of a stimulus is known as the "strength-duration relationship". Objective: To test the "strength-duration relationship", so as to improve paired-pulse TMS protocols, and to apply the results to develop new repetitive TMS (rTMS) methods. Methods: Four protocols were investigated separately: short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), short-interval intracortical facilitation (SICF) and long-interval intracortical inhibition (LICI). First, various stimulus parameters were tested to identify those yielding the largest facilitation or inhibition of the motor evoked potential (MEP) in each participant. Using these parameters, paired-pulse stimulations were repeated every five seconds for 30 minutes (repetitive paired-pulse stimulation, rPPS). The after-effects of rPPS were measured using MEP amplitude as an index of motor-cortical excitability. Results: Altogether, the effect of changing PW was similar to that of changing the stimulus intensity in the conventional settings. The best parameters were different for each participant. When these parameters were used, rPPS based on either SICF or ICF induced an increase in MEP amplitude. Conclusions: PW was introduced as a new parameter in paired-pulse TMS. Modulation of PW influenced the results of paired-pulse protocols. rPPS using facilitatory protocols can be a good candidate to induce enhancement of motor-cortical excitability.
... A variation of the cTMS2 circuit, cTMS3 shown in Fig. 10.1(e), uses two positively charged capacitors and four switches (Peterchev and Murphy, 2011). Compared to cTMS2, cTMS3 has some technical implementation advantages and allows the generation of two additional coil voltage levels. ...
Chapter
This chapter provides overview of the state of the art of transcranial magnetic stimulation (TMS) devices, including pulse sources with flexible control of the output waveform parameters and a wide variety of coil designs. It discusses technologies for accurate TMS targeting, including electric field models, frameless stereotaxy, and robotic coil holders. The chapter addresses technological aspects of ancillary coil effects such as heating, noise, vibration, and scalp stimulation. TMS requires high energy pulses that present a technical challenge for the design of practical, flexible, and efficient pulse sources. The chapter covers technical considerations for the integration of TMS and neuroimaging devices. It discusses various coil configurations and their electric field characteristics as well as technical advances in coil field modelling, positioning systems, efficiency and cooling, noise and scalp stimulation, and sham. The chapter summarizes technical considerations for the integration of TMS and neuroimaging devices.
... The temporal aspects of TMS dosing can be divided into the temporal aspects of each individual pulse (including its shape, width, and directionality), and the train of repeated pulses (including frequency, duration, and number of pulses per train). Two novel developments in the temporal aspects of individual pulses include controllable pulse shape TMS (cTMS) (94)(95)(96) and rotating field TMS (rfTMS) (97). Cortical response to TMS depends on the width of the pulse, and sTMS synchronized transcranial magnetic stimulation, dTMS deep transcranial magnetic stimulation, HF-TMS high-frequency transcranial magnetic stimulation, LF-TMS low-frequency transcranial magnetic stimulation, TBS theta-burst stimulation, iTBS intermittent theta-burst stimulation, cTBS continuous theta-burst stimulation, LFMS low field magnetic stimulation, IAF individual alpha frequency (average 9 Hz), DLPFC dorsolateral prefrontal cortex only recently have we had access to devices that allow independent user control of this aspect of temporal dosing (98). ...
Article
Full-text available
Noninvasive neuromodulation refers to a family of device-based interventions that apply electrical or magnetic fields, either at convulsive or subconvulsive levels, to the brain through the intact skull to modulate neural function. This is a rapidly evolving field, with new research emerging regarding the various roles that these devices can play both in studying the neural mechanisms underlying mood and anxiety disorders, and in treating pharmacoresistant conditions either on their own or in combination with other therapies. Each neuromodulation modality has its pros and cons and should be carefully chosen after weighing the risks and benefits. This manuscript reviews some of the most exciting developments in this field over the past year and emphasizes themes that are emerging as being important for these tools to fulfill their potential to transform how we study and treat mood and anxiety disorders. Key among these themes is the concept of how we understand the “dose” of the stimulation, and how exogenously applied fields interact with endogenous brain activity. Refining the concept of dose will ultimately be important in allowing clinicians and researchers to apply the procedure with precision to engage the targeted network to achieve the desired effects in each individual. The large parameter space defining dose of neuromodulation makes interpreting the literature on safety and efficacy challenging and highlights the need for clear and accurate reporting of the spatial, temporal, and contextual features of dosage to make the emerging literature base as informative as possible. Ultimately, the impact of noninvasive neuromodulation devices is potentially transformational given their utility in providing mechanistic insight into the circuit-based and oscillatory origins of mood and anxiety disorders, as well as providing therapeutic interventions rationally designed to target disease-related processes.
... Additionally, MEP latencies of APdirected stimuli were shown to vary with pulse duration. Direct comparison of the present results with commercially-available devices is difficult since most permit little or no control over pulse width Rothkegel et al., 2010) and exhibit a sinusoidal pulse shape which differs from the more rectangular pulses delivered via the cTMS device (Peterchev et al., 2011). ...
Article
Full-text available
To compare the strength-duration (S-D) time constants of motor cortex structures activated by current pulses oriented posterior-anterior (PA) or anterior-posterior (AP) across the central sulcus. Motor threshold and input-output curve, along with motor evoked potential (MEP) latencies, of first dorsal interosseus were determined at pulse widths of 30, 60, and 120μs using a controllable pulse parameter (cTMS) device, with the coil oriented PA or AP. These were used to estimate the S-D time constant and we compared with data for responses evoked by cTMS of the ulnar nerve at the elbow. The S-D time constant with PA was shorter than for AP stimulation (230.9±97.2 vs. 294.2±90.9μs; p<0.001). These values were similar to those calculated after stimulation of ulnar nerve (197±47μs). MEP latencies to AP, but not PA stimulation were affected by pulse width, showing longer latencies following short duration stimuli. PA and AP stimuli appear to activate the axons of neurons with different time constants. Short duration AP pulses are more selective than longer pulses in recruiting longer latency corticospinal output. More selective stimulation of neural elements may be achieved by manipulating pulse width and orientation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
... LI-rMS stimulation was delivered to cells in the incubator with a custom built round coil (8 mm inside diameter, 16.2 mm outside diameter, 10 mm thickness, 0.25 mm copper wire, 6.1 U resistance, 462 turns) placed 3 mm from the coverslip (Fig. 1A) and driven by a 12 V magnetic pulse generator: a simple resistor-inductor circuit under control of a programmable (C-based code) micro-controller card (CardLogix, USA). The non-sinusoidal monophasic pulse [25] had a measured 320 ms rise time and generated an intensity of 13 mT as measured at the target cells by hall effect (ss94a2d, Honeywell, USA) and assessed by computational modeling using Matlab (Mathworks, USA; Fig. 1B,C). Coil temperature did not rise above 37 C, ruling out confounding effects of temperature change. ...
Article
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Background: Repetitive transcranial magnetic stimulation is increasingly used as a treatment for neurological dysfunction. Therapeutic effects have been reported for low intensity rTMS (LI-rTMS) although these remain poorly understood. Objective: Our study describes for the first time a systematic comparison of the cellular and molecular changes in neurons in vitro induced by low intensity magnetic stimulation at different frequencies. Methods: We applied 5 different low intensity repetitive magnetic stimulation (LI-rMS) protocols to neuron-enriched primary cortical cultures for 4 days and assessed survival, and morphological and biochemical change. Results: We show pattern-specific effects of LI-rMS: simple frequency pulse trains (10 Hz and 100 Hz) impaired cell survival, while more complex stimulation patterns (theta-burst and a biomimetic frequency) did not. Moreover, only 1 Hz stimulation modified neuronal morphology, inhibiting neurite outgrowth. To understand mechanisms underlying these differential effects, we measured intracellular calcium concentration during LI-rMS and subsequent changes in gene expression. All LI-rMS frequencies increased intracellular calcium, but rather than influx from the extracellular milieu typical of depolarization, all frequencies induced calcium release from neuronal intracellular stores. Furthermore, we observed pattern-specific changes in expression of genes related to apoptosis and neurite outgrowth, consistent with our morphological data on cell survival and neurite branching. Conclusions: Thus, in addition to the known effects on cortical excitability and synaptic plasticity, our data demonstrate that LI-rMS can change the survival and structural complexity of neurons. These findings provide a cellular and molecular framework for understanding what low intensity magnetic stimulation may contribute to human rTMS outcomes.
... LI-rMS stimulation was delivered to cells in the incubator with a custom built round coil (8 mm inside diameter, 16.2 mm outside diameter, 10 mm thickness, 0.25 mm copper wire, 6.1 U resistance, 462 turns) placed 3 mm from the coverslip (Fig. 1A) and driven by a 12 V magnetic pulse generator: a simple resistor-inductor circuit under control of a programmable (C-based code) micro-controller card (CardLogix, USA). The non-sinusoidal monophasic pulse [25] had a measured 320 ms rise time and generated an intensity of 13 mT as measured at the target cells by hall effect (ss94a2d, Honeywell, USA) and assessed by computational modeling using Matlab (Mathworks, USA; Fig. 1B,C). Coil temperature did not rise above 37 C, ruling out confounding effects of temperature change. ...
Article
Full-text available
Background: Repetitive transcranial magnetic stimulation is increasingly used as a treatment for neurological dysfunction. Therapeutic effects have been reported for low intensity rTMS (LI-rTMS) although these remain poorly understood. Objective: Our study describes for the first time a systematic comparison of the cellular and molecular changes in neurons in vitro induced by low intensity magnetic stimulation at different frequencies. Methods: We applied 5 different low intensity repetitive magnetic stimulation (LI-rMS) protocols to neuron-enriched primary cortical cultures for 4 days and assessed survival, and morphological and biochemical change. Results: We show pattern-specific effects of LI-rMS: simple frequency pulse trains (10 Hz and 100 Hz) impaired cell survival, while more complex stimulation patterns (theta-burst and a biomimetic frequency) did not. Moreover, only 1 Hz stimulation modified neuronal morphology, inhibiting neurite outgrowth. To understand mechanisms underlying these differential effects, we measured intracellular calcium concentration during LI-rMS and subsequent changes in gene expression. All LI-rMS frequencies increased intracellular calcium, but rather than influx from the extracellular milieu typical of depolarization, all frequencies induced calcium release from neuronal intracellular stores. Furthermore, we observed pattern-specific changes in expression of genes related to apoptosis and neurite outgrowth, consistent with our morphological data on cell survival and neurite branching. Conclusions: Thus, in addition to the known effects on cortical excitability and synaptic plasticity, our data demonstrate that LI-rMS can change the survival and structural complexity of neurons. These findings provide a cellular and molecular framework for understanding what low intensity magnetic stimulation may contribute to human rTMS outcomes.
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
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Background: Transcranial magnetic stimulation (TMS) is a clinically effective therapeutic instrument used to modulate neural activity. Despite three decades of research, two challenging issues remain, the possibility of changing the 1) stimulated spot and 2) stimulation type (real or sham) without physically moving the coil. Objective: In this study, a second-generation programmable TMS (pTMS2) device with advanced stimulus shaping is introduced that uses a 5-level cascaded H-bridge inverter and phase-shifted pulse-width modulation (PWM). The principal idea of this research is to obtain real, sham, and multi-locus stimulation using the same TMS system. Methods: We propose a two-channel modulation-based magnetic pulse generator and a novel coil arrangement, consisting of two circular coils with a physical distance of 20 mm between the coils and a control method for modifying the effective stimulus intensity, which leads to the live steerability of the target and type of stimulation. Results: Based on the measured system performance, the stimulation profile can be steered ± 20 mm along a line from the centroid of the coil locations by modifying the modulation index. Conclusion: The proposed system supports electronic control of the stimulation spot without physical coil movement, resulting in tunable modulation of targets, which is a crucial step towards automated TMS machines.
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.
Conference Paper
The concept of a portable, wearable system for repetitive transcranial stimulation (rTMS) has attracted widespread attention, but significant power and field intensity requirements remain a key challenge. Here, a circuit topology is described that significantly increases induced electric field intensity over that attainable with similar current levels and coils in conventional rTMS systems. The resultant electric field is essentially monophasic, and has a controllable, shortened duration. The system is demonstrated in a compact circuit implementation for which an electric field of 94 V/m at a depth of 2 cm is measured (147 V/m at 1 cm depth) with a power supply voltage of 80 V, a maximum current of 500 A, and an effective pulse duration (half amplitude width) of 7 µsec. The peak electric field is on the same order as that of commercially available systems at full power and comparable depths. An electric field boost of 5x is demonstrated in comparison with our system operated conventionally, employing a 70 µsec rise time. It is shown that the power requirements for rTMS systems depend on the square of the product of electric field Ep and pulse duration tp, and that the proposed circuit technique enables continuous variation and optimization of the tradeoff between Ep and tp. It is shown that the electric field induced in a medium such as the human brain cortex at a specific depth is proportional to the voltage generated in a given loop of the generating coil, which allows insights into techniques for its optimization. This rTMS electric field enhancement strategy, termed 'boost rTMS (rbTMS)' is expected to increase the effectiveness of neural stimulation, and allow greater flexibility in the design of portable rTMS power systems.Clinical Relevance- This study aims to facilitate a compact, battery-powered rTMS prototype with enhanced electric field which will permit broader and more convenient rTMS treatment at home, in a small clinic, vessel, or field hospital, and potentially, on an ambulatory basis.
Preprint
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A bstract Background Transcranial magnetic stimulation (TMS) is a clinically effective therapeutic instrument used to modulate neural activity. Despite three decades of research, two challenging issues remain, the possibility of changing the 1) stimulated spot and 2) stimulation type (real or sham) without physically moving the coil. Objective In this study, a second-generation programmable TMS (pTMS2) device with advanced stimulus shaping is introduced that uses a 5-level cascaded H-bridge inverter and phase-shifted pulse-width modulation (PWM). The principal idea of this research is to obtain real, sham, and multi-locus stimulation with the same TMS system. Methods We propose a two-channel modulation-based magnetic pulse generator and a novel coil arrangement, consisting of two circular coils with a physical distance of 20 mm between the coils and a control method for modifying the effective stimulus intensity, which leads to the live steerability of the location and type of stimulation. Results Based on the measured system performance, the stimulation profile can be steered ± 20 mm along a line from the centroid of the coil locations by modifying the modulation index. Conclusion The proposed system supports electronic control of the stimulation spot without physical coil movement, resulting in tunable modulation of targets, which is a crucial step towards automated TMS machines.
Article
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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.
Chapter
Transcranial magnetic stimulation (TMS) is a noninvasive method for focal brain stimulation, with applications in research, diagnostics, and treatment. In basic research, TMS can help establish a causal link between a brain circuit and a behavior. Clinically, repetitive TMS can alter the long-term excitability of specific brain regions to treat psychiatric and neurological disorders. This chapter aims to support engineers and researchers to understand and innovate TMS technology. It introduces the basics of TMS spanning engineering, physics, biophysics, paradigms, and applications. First, the principles of TMS devices are explained including the electrical circuit topologies and efficiency of the pulse generator as well as the design of the stimulation coil. Ancillary effects such as heating, electromagnetic forces, and interactions with other devices are considered. Then, the underlying physics and its modeling are presented, including the magnetic field of the coil and the impact of the subject’s head on the induced electric field. This is followed by a description of the biophysics of neuronal activation due to TMS, including the cable equation, leaky integrate-and-fire neural membrane dynamics, and morphologically realistic neuron models. Various methods to measure the responses to TMS are summarized, spanning observations of behavior, electromyography, epidural recordings, electroencephalography, functional near-infrared spectroscopy, functional magnetic resonance imaging, and positron emission tomography. The chapter concludes with an overview of stimulation paradigms encompassing single-pulse, paired-pulse, and repetitive TMS, along with their applications in basic research and the clinic. The chapter includes ten problems that cover the presented material.
Article
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To improve the stimulation efficiency of transcranial magnetic stimulation (TMS) and reduce the size and power consumption of the overall circuit, a compact and efficient capacitor charging power supply using an inductor–capacitor–inductor–capacitor resonant converter (LC–LC RC) is designed in this study. The LC–LC RC has the characteristics of low power consumption, high efficiency and uses the voltage gain of the resonant circuit itself and a voltage doubler rectifier circuit instead of the transformer to reduce the size and weight of the overall circuit. A detailed ac analysis with fundamental frequency approximation of the LC–LC RC is presented. Expressions for converter gain, operating condition of the converter as a constant‐current power supply, and condition of the converter voltage and current zero‐phase difference are derived. In addition, RC design value conditions for the minimum resonant network size are derived. An experimental 1.05 A 120 V prototype converter is designed, developed, and tested to verify the theoretical analysis. Experimental results indicate that this circuit is suitable for use in capacitor charging to increase the stimulation performance of TMS.
Article
In order to increase the security and flexibility of the magnetic field generator, a multi-channel parameters adjustable (MCPA) magnetic field generator is designed and implemented in this paper. The circuit topology of the MCPA magnetic field generator is presented. The working principle of MCPA is analyzed. The pulse current is measured and verified by experiments. The results show that the pulsed current amplitude is adjustable under 1000 A, the adjustment range of the effective pulse width is 0–160 µs, and the adjustment range of the frequency is 1–10 Hz. The magnetic field intensity at 2.5 cm below the scalp of the brain was measured when the three channels were working at the same time. It can be seen that the intensity of the magnetic field in the central area is apparently higher than that in the surrounding. The channels of MCPA can also be chosen flexibly as needed. Therefore, it has a very high application and research value in the field of biological magnetism therapy.
Chapter
Transcranial magnetic stimulation (TMS) is increasingly used as a diagnostic and therapeutic tool for neuropsychiatric disorders. TMS for treatment of depression during pregnancy is an appealing alternative to fetus-threatening drugs. However, there are no studies to date that evaluate the safety of TMS for a pregnant mother and her fetus. Two scenarios are possible in practice: (i) pregnant woman as a patient and (ii) pregnant woman as an operator. The goal of the present study is to estimate maximum field exposures for the fetus in both scenarios. A full-body finite element method (FEM) compatible model of a pregnant woman with about 100 tissue parts has been developed for the present study. This model allows detailed computations of induced current/electric field in every tissue given different locations of a figure-eight coil, a biphasic pulse, common TMS pulse durations, and using different values of the TMS intensity measured in standard motor threshold (SMT) units. Along with the numerical simulations, we use a simple analytical estimation model; both approaches confirm and augment each other. Our simulation/analytical results estimate the maximum peak values of the electric field in the fetal area and beyond in 48 (operator/patient) representative cases, for every fetal tissue separately and for a TMS intensity of one SMT unit. This study provides the first detailed data on risk to fetal exposure to induced fields by TMS in pregnant patients and pregnant operators. It is expandable to any patient/operator configuration by applying a simple analytical upper estimate of field strength/eddy current density.
Article
Motor evoked potentials (MEPs) are widely used for biomarkers and dose individualization in transcranial stimulation. The large variability of MEPs requires sophisticated methods of analysis to extract information fast and correctly. Development and testing of such methods relies on the availability for realistic models of MEP generation, which are presently lacking. This work presents a statistical model that can simulate long sequences of individualized MEP amplitude data with properties matching experimental observations. The MEP model includes three sources of trial-to-trial variability: excitability fluctuations, variability in the neural and muscular pathways, and physiological and measurement noise. It also generates virtual human subject data from statistics of population variability. All parameters are extracted as statistical distributions from experimental data from the literature. The model exhibits previously described features, such as stimulus-intensity-dependent MEP amplitude distributions, including bimodal ones. The model can generate long sequences of test data for individual subjects with specified parameters or for subjects from a virtual population. The presented MEP model is the most detailed to date and can be used for the development and implementation of dosing and biomarker estimation algorithms for transcranial stimulation.
Article
The influence of pulse width, pulse waveform and current direction on transcranial magnetic stimulation (TMS) outcomes is of critical importance. However, their effects have only been investigated indirectly with motor-evoked potentials (MEP). By combining TMS and EEG it is possible to examine how these factors affect evoked activity from the cortex and compare that with the effects on MEP. We used a new controllable TMS device (cTMS) to vary systematically pulse width, pulse waveform and current direction and explore their effects on global and local TMS-evoked EEG response. In 19 healthy volunteers we measured (1) resting motor threshold (RMT) as an estimate of corticospinal excitability; (2) global mean field power (GMFP) as an estimate of global cortical excitability; and (3) local mean field power (LMFP) as an estimate of local cortical excitability. RMT was lower with monophasic posterior-to-anterior (PA) pulses that have a longer pulse width (p < 0.001). After adjusting for the individual motor threshold of each pulse type we found that (a) GMFP was higher with monophasic pulses (p < 0.001); (b) LMFP was higher with longer pulse width (p = 0.015); (c) early TEP polarity was modulated depending on the current direction (p = 0.01). Despite normalizing stimulus intensity to RMT, we found that local and global responses to TMS vary depending on pulse parameters. Since EEG responses can vary independently of the MEP, titrating parameters of TMS in relation to MEP threshold is not a useful way of ensuring that a constant set of neurons is activated within a cortical area.
Article
To improve the energy utilization of magnetic field generators for biological applications, a multifunctional energy-saving magnetic field generator (ESMFG) is presented. It is capable of producing both an alternating magnetic field (AMF) and a bipolar pulse magnetic field (BPMF) with high energy-saving and energy-reuse rates. Based on a theoretical analysis of an RLC second-order circuit, the energy-saving and energy-reuse rates of both types of magnetic fields can be calculated and are found to have acceptable values. The results of an experimental study using the proposed generator show that for the BPMF, the peak current reaches 130 A and the intensity reaches 70.3 mT. For the AMF, the intensity is 11.0 mT and the RMS current is 20 A. The energy-saving and energy-reuse rates for the AMF generator are 61.3% and 63.5%, respectively, while for the BPMF generator, the energy-saving rate is 33.6%. Thus, the proposed ESMFG has excellent potential for use in biomedical applications.
Conference Paper
Transcranial magnetic stimulation (TMS) for treatment of depression during pregnancy is an appealing alternative to fetus-threatening drugs. However, no studies to date have been performed that evaluate the safety of TMS for a pregnant mother patient and her fetus. A full-body FEM model of a pregnant woman with about 100 tissue parts has been developed specifically for the present study. This model allows accurate computations of induced electric field in every tissue given different locations of a shape-eight coil, a biphasic pulse, common TMS pulse durations, and using different values of the TMS intensity measured in SMT (Standard Motor Threshold) units. Our simulation results estimate the maximum peak values of the electric field in the fetal area for every fetal tissue separately and for the TMS intensity of one SMT unit.
Chapter
Treatment-resistant depression remains an important clinical problem in need of novel treatment solutions. Electro-convulsive therapy and transcranial magnetic stimulation are two neuromodulation techniques with promise in the treatment of severe and chronic depression. In this chapter we present the theory and research support for these two types of therapies. We discuss their strengths and limitations and propose clinical and research future directions for treatment in this area.
Data
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Details on the used nominal axon model. (PDF)
Article
Local field potential (LFP) signals of the rat hippocampus were recorded under noninvasive focused ultrasound stimulation (FUS) with different ultrasonic powers. The LFP mean absolute power was calculated with the Welch algorithm at the delta, theta, alpha, beta, and gamma frequency bands. The experimental results demonstrate that the LFP mean absolute power at different frequency bands increases as the ultrasound power increases.
Article
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Magnetic stimulation of neural tissue is an attractive technology because neural excitation may be affected without requiring implantation of electrodes. Pulsed discharge circuits are typically implemented for clinical magnetic stimulation systems. However, pulsed discharge systems can confound in-vitro experimentation. As an alternative to pulsed discharge circuits, we present a circuit to deliver asymmetric current pulses for generation of the magnetic field. We scaled the system down by using ferrite cores for the excitation coil. The scaled system allows observation using electrophysiological techniques and preparations not commonly used for investigation of magnetic stimulation. The design was refined using a comprehensive set of design equations. Circuit modeling and simulation demonstrate that the proposed system is effective for stimulating neural tissue with electric-field gradients generated by time-varying magnetic fields. System performance is verified through electrical test.
Conference Paper
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We are reporting on a High-Voltage Impulse Generator, which consists of a step-up transformer, which is driven by new HV-IGBTs (High-Voltage Isolated Gate Bipolar Transistors). The new HV-IGBTs are individually packaged silicon-dies intended for Pulsed-Power Applications. The silicon dies are normally packaged in large modules for locomotive motor drives and similar traction applications. In our work we used the Powerex QIS4506001 discrete IGBT and the QRS4506001 discrete diode, both with a nominal rating of 4500V/60A, derived from continuous- duty applications. Our experiments have shown that the devices are capable of handling currents in excess of 1 kA during pulsed operation.
Article
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Magnetic seizure therapy (MST) is a novel means of performing convulsive therapy using rapidly alternating strong magnetic fields. MST offers greater control of intracerebral current intensity than is possible with electroconvulsive therapy (ECT). These features may result in a superior cognitive side effect profile for MST, while possibly retaining the efficacy of ECT. The objective of this study was to determine whether MST and ECT differ in seizure characteristics, and acute objective and subjective cognitive side effects. A total of 10 inpatients in a major depressive episode referred for ECT were enrolled in this randomized, within-subject, double-masked trial. Seizure threshold was determined with MST and ECT in the first two sessions of a course of convulsive therapy, with order randomized. The remaining two sessions consisted of suprathreshold stimulation with MST and ECT. A neuropsychological battery and side effect rating scale were administered by a masked rater before and after each session. Tonic-clonic seizures were elicited with MST in all patients. Compared to ECT, MST seizures had shorter duration, lower ictal EEG amplitude, and less postictal suppression. Patients had fewer subjective side effects and recovered orientation more quickly with MST than ECT. MST was also superior to ECT on measures of attention, retrograde amnesia, and category fluency. Magnetic seizure induction in patients with depression is feasible, and appears to have a superior acute side effect profile than ECT. Future research will be needed to establish whether MST has antidepressant efficacy.
Article
We describe a novel transcranial magnetic stimulation (TMS) device that uses a circuit topology incorporating two energy-storage capacitors and two insulated-gate bipolar transistors (IGBTs) to generate near-rectangular electric field E-field) pulses with adjustable number, polarity, duration, and amplitude of the pulse phases. This controllable-pulse-parameter TMS (cTMS) device can induce E-field pulses with phase widths of 5-200 µs and positive/negative phase amplitude ratio of 1-10. Compared to conventional monophasic and biphasic TMS, cTMS reduces energy dissipation by 78-82% and 55-57% and decreases coil heating by 15-33% and 31-41%, respectively. We demonstrate repetitive TMS (rTMS) trains of 3,000 pulses at frequencies up to 50 Hz with E-field pulse amplitude and width variability of less than 1.7% and 1%, respectively. The reduced power consumption and coil heating, and the flexible pulse parameter adjustment offered by cTMS could enhance existing TMS paradigms and could enable novel research and clinical applications with potentially enhanced potency.
Article
The energy efficiency of stimulation is an important consideration for battery-powered implantable stimulators. We used a genetic algorithm (GA) to determine the energy-optimal waveform shape for neural stimulation. The GA was coupled to a computational model of extracellular stimulation of a mammalian myelinated axon. As the GA progressed, waveforms became increasingly energy efficient and converged upon an energy-optimal shape. The results of the GA were consistent across several trials, and resulting waveforms resembled truncated Gaussian curves. When constrained to monophasic cathodic waveforms, the GA produced waveforms that were symmetric about the peak, which occurred approximately during the middle of the pulse. However, when the cathodic waveforms were coupled to rectangular charge-balancing anodic pulses, the location and sharpness of the peak varied with the duration and timing (i.e., before or after the cathodic phase) of the anodic phase. In a model of a population of mammalian axons and in vivo experiments on a cat sciatic nerve, the GA-optimized waveforms were more energy efficient and charge efficient than several conventional waveform shapes used in neural stimulation. If used in implantable neural stimulators, GA-optimized waveforms could prolong battery life, thereby reducing the frequency of recharge intervals, the volume of implanted pulse generators, and the costs and risks of battery-replacement surgeries.
Article
In this work we address the problem of stimulating nervous tissue with the minimal necessary energy at reduced/minimal charge. Charge minimization is related to a valid safety concern (avoidance and reduction of stimulation-induced tissue and electrode damage). Energy minimization plays a role in battery-driven electrical or magnetic stimulation systems (increased lifetime, repetition rates, reduction of power requirements, thermal management). Extensive new theoretical results are derived by employing an optimal control theory framework. These results include derivation of the optimal electrical stimulation waveform for a mixed energy/charge minimization problem, derivation of the charge-balanced energy-minimal electrical stimulation waveform, solutions of a pure charge minimization problem with and without a constraint on the stimulation amplitude, and derivation of the energy-minimal magnetic stimulation waveform. Depending on the set stimulus pulse duration, energy and charge reductions of up to 80% are deemed possible. Results are verified in simulations with an active, mammalian-like nerve fiber model.
Article
The intensity of transcranial magnetic stimulation (TMS) is typically adjusted by changing the amplitude of the induced electrical field, while its duration is fixed. Here we examined the influence of two different pulse durations on several physiological parameters of primary motor cortex excitability obtained using single pulse TMS. A Magstim Bistim(2) stimulator was used to produce TMS pulses of two distinct durations. For either pulse duration we measured, in healthy volunteers, resting and active motor thresholds, recruitment curves of motor evoked potentials in relaxed and contracting hand muscles as well as contralateral (cSP) and ipsilateral (iSP) cortical silent periods. Motor thresholds decreased by 20% using a 1.4 times longer TMS pulse compared to the standard pulse, while there was no significant effect on threshold adjusted measurements of cortical excitability. The longer pulse duration reduced pulse-to-pulse variability in cSP. The strength of a TMS pulse can be adjusted both by amplitude or pulse duration. TMS pulse duration does not affect threshold-adjusted single pulse measures of motor cortex excitability. Using longer TMS pulses might be an alternative in subjects with very high motor threshold. Pulse duration might not be relevant as long as TMS intensity is threshold-adapted. This is important when comparing studies performed with different stimulator types.
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.
Article
To optimize the clinical uses of repetitive transcranial magnetic stimulation (rTMS), we compared the effects of rTMS on somatosensory-evoked potentials (SEPs) and regional cerebral blood flow (rCBF) using different phases (monophasic vs. biphasic) or frequencies (0.2Hz vs. 0.8Hz) of stimulation. In the first experiment, different phases were compared (0.2Hz monophasic vs. 0.2Hz biphasic). Biphasic 1Hz or sham condition served as controls. The second experiment was to explore the effect of frequencies (0.2Hz vs. 0.8Hz) using the monophasic stimulation. Substhreshold TMS was applied 250 times over the left premotor cortex. Single photon emission computed tomography (SPECT) was performed before and after monophasic 0.2Hz or biphasic 1Hz rTMS. Monophasic rTMS of both 0.2 and 0.8Hz significantly increased the ratio of N30 amplitudes as compared with sham rTMS, whereas biphasic stimulation showed no significant effects. SPECT showed increased rCBF in motor cortices after monophasic 0.2Hz rTMS, but not after biphasic 1Hz stimulation. Monophasic rTMS exerted more profound effects on SEPs and rCBF than biphasic rTMS over the premotor cortex. Monophasic rTMS over the premotor cortex could be clinically more useful than biphasic rTMS.
We describe the first investigation into the effect on stimulation efficiency of varying the output of a commercial magnetic stimulator based on our original clinical design. Over the range of magnetic field waveforms considered, it is shown that the stored energy required to achieve stimulation, both cortically and in the periphery, varies by approximately 2:1. Greater efficiency is obtained by using shorter risetime magnetic fields. This results in more effective stimuli for the same stored energy, or, for the same stimulus, a decrease in energy storage, power dissipation and peak currents, thus simplifying hardware design. A novel method of processing the data obtained from different waveforms is presented which enables neural membrane time constant to be calculated. Data from normal subjects is presented showing both peripheral and neural time constants to be of order 150 microseconds. The cortical measurements represent the first non-invasive determination of cortical membrane time constant in man. Time constant measurements using magnetic stimulation may be clinically useful because they give information concerning the electrical properties of the nervous system not available from present techniques. Finally a method of quantifying the output of magnetic stimulators and coils is described which enables laboratory comparisons to be made, and takes into account magnetic field waveforms and coil geometry. The proposed symbol for this new measurement is Et150 with units volt seconds/meter.
Article
The use of a time-varying magnetic field to induce a sufficiently strong current to stimulate living tissue was first reported by d'Arsonval in 1896. Since then, there have been many studies in what is now called magnetic stimulation. This paper traces the history of this field from d'Arsonval to its present use in neurophysiology.
Article
Magnetic stimulation of the human brain is performed in clinical and research settings, but the site of activation has not been clearly localized in humans or other species. We used a set of magnetic stimulus coils with different field profiles to isolate movement of single digits at motor threshold and to calculate corresponding electric field strengths at various distances beneath the scalp. Two coils could produce the same electric field intensity at only 1 point. Thus, we could estimate the depth of stimulation by finding the intersection of the electric field plots, which were then superimposed on MRIs of the underlying brain. In each of 3 subjects the field plots intersected at the crown of a gyrus, in the region of the central sulcus, an near the level of the gray-white junction. This position and the electric field orientation support localization to layer VI of cerebral cortex.
Article
The possibility of neural damage during extracranial brain stimulation for motor evoked potentials (MEPs) is discussed from the perspective of animal studies in which the stimulating electrodes were in direct contact with the brain. These data indicate that the charge per phase used in most of the extracranial MEP protocols is sufficient to induce neural damage if the stimulation is applied continuously for several hours. However, in most cases dispersion of the stimulus current in the extracranial tissue and skull is probably adequate to attenuate the stimulus charge density at the brain surface to a safe level (less than approximately 40 microC/cm2 X ph). However, the possibility exists that low resistance paths between the stimulating electrode and the brain may give rise to foci of high charge density. The possibility of such focusing may be less with magnetic field than with direct electrical field stimulation. We stress the need for additional animal studies designed to delineate a range of safe stimulus parameters for this particular technique.
Article
The safety of single and repetitive (paired and quadruple) focal transcranial magnetic stimuli as possible inducers of epileptic discharges or clinically manifest seizures was investigated in 21 patients with intractable epilepsy during invasive presurgical monitoring. Subdural and/or intracerebral depth electrodes had been implanted in close proximity to the suspected epileptogenic zone, and the anticonvulsant medication had been reduced. Focal transcranial magnetic stimuli were applied by a Magstim QuadroPulse magnetic stimulator over the hand area of the motor cortex ipsilateral to the epileptogenic focus at intensities of 120% and 150% of motor threshold and additionally as close as possible to the suspected epileptogenic zone at 40-100% of maximal stimulator output. Stimulation did not induce any complex partial or secondary generalized tonic-clonic seizures. One patient with hippocampal sclerosis experienced an aura associated with rhythmic electroencephalographic discharges restricted to the ipsilateral intrahippocampal depth electrode after stimulation over his left temporal lobe. This patient, however, also had frequent spontaneously occurring auras with focal ictal discharges originating from this hippocampus. Interictal discharges were not influenced significantly by single or repetitive magnetic stimuli. In conclusion, from this study there is no evidence that single or serial focal transcranial magnetic stimuli activate epileptogenic foci. At least four high-frequency repetitive stimuli of high intensity may thus be applied with a low risk of seizure induction even in patients with low seizure threshold.
Article
A detailed analysis of the membrane voltage rise commensurate with the electrical charging circuit of a typical magnetic stimulator is presented. The analysis shows how the membrane voltage is linked to the energy, reluctance, and resonant frequency of the electrical charging circuit. There is an optimum resonant frequency for any nerve membrane depending on its capacitive time constant. The analysis also shows why a larger membrane voltage will be registered on the second phase of a biphasic pulse excitation [1]. Typical constraints on three key quantities voltage, current, and silicone controlled rectifier (SCR) switching time dictate key components such as capacitance, inductance, and choice of turns.
Article
In a blinded cross-over design, 10 healthy controls received 900 monophasic and biphasic repetitive transcranial magnetic stimuli over the primary motor cortex. Stimulation frequency was 1 Hz, and stimulation intensity 90% of the individual resting motor threshold. Suprathreshold stimuli applied at 0.1 Hz before and after repetitive stimulation controlled for changes in corticospinal excitability. We found a lasting corticospinal inhibition that was significantly more pronounced after monophasic than after biphasic repetitive transcranial magnetic stimulation (motor evoked potential amplitude reduced by 35 +/- 20% vs 12 +/- 37%, mean+/- s.d.). We propose that the current flow in the coil plays a significant role in optimising after effects, and asymmetric current flow may be particularly efficient in building up tissue polarization.
Article
Transcranial magnetic stimulation requires a great deal of power, which mandates bulky power supplies and produces rapid coil heating. The authors describe the construction, modeling, and testing of an iron-core TMS coil that reduces power requirements and heat generation substantially, while improving the penetration of the magnetic field. Experimental measurements and numeric boundary element analysis show that the iron-core stimulation coil induces much stronger electrical fields, allows greater charge recovery, and generates less heat than air-core counterparts when excited on a constant-energy basis. These advantages are magnified in constant-effect comparisons. Examples are given in which the iron-core coil allows more effective operation in research and clinical applications.
Article
Transcranial magnetic stimulation (TMS) is a noninvasive technique for direct stimulation of the neocortex. In the last two decades it is successfully applied in the study of motor and sensory physiology. TMS uses the indirect induction of electrical fields in the brain generated by intense changes of magnetic fields applied to the scalp. It encompasses two widely used waveform configurations: mono-phasic magnetic pulses induce a single current in the brain while biphasic pulses induce at least two currents of inverse direction. As has been shown for the motor cortex, efficacy of repetitive transcranial magnetic stimulation (rTMS) may depend on pulse configuration. In order to clarify this question with regard to visual perception, static contrast sensitivities (sCS) were evaluated before, during, immediately after and 10 minutes after monophasic and biphasic low frequency (1 Hz) rTMS applied to the occipital cortex of 15 healthy subjects. The intensity of stimulation was the phosphene threshold of each individual subject. Using 4 c/d spatial frequency, significant sCS loss was found during and immediately after 10 min of monophasic stimulation, while biphasic stimulation resulted in no significant effect. Ten minutes after the end of stimulation, the sCS values were at baseline level again. However, reversed current flow direction resulted in an increased efficacy of biphasic and decreased efficacy of monophasic stimulation. Our results are in agreement with previous findings showing that primary visual functions, such as contrast detection, can be transiently altered by low frequency transcranial magnetic stimulation. However the effect of modulation significantly depends on the current waveform and direction.
Article
Stimulus-response curves for motor evoked potentials (MEPs) induced in a hand muscle by transcranial magnetic stimulation (TMS) were constructed for 42 subjects with the aim of identifying differences related to age and sex. There was no effect of age on the resting threshold to TMS, the maximal amplitude of the MEP that could be evoked (MEP(max)) or the maximal slope of the stimulus-response curve. However, higher stimulus intensities were required to achieve both MEP(max) and the maximal slope in the older subjects. The trial-to-trial variability of MEPs was greater in the older subjects, particularly at intensities near threshold. There was a significant interaction between age, threshold and trial-to-trial variability of MEP amplitude. Overall, MEP variability fell markedly as stimulus intensity increased above threshold but less rapidly in older than in younger subjects. Females tended to have larger MEP variability than males, but age and threshold were much stronger modulators than sex. These differences in input-output characteristics are likely to be due either to a decreased number of spinal motoneurones being activated synchronously in older subjects, or to the activation of the same number of motoneurones in a less synchronous manner, leading to phase cancellation in the surface electromyogram.
Article
To compare motor evoked potentials (MEPs) elicited by short train, monophasic, repetitive transcranial magnetic stimulations (rTMS) with those by short train, biphasic rTMS. Subjects were 13 healthy volunteers. Surface electromyographic (EMG) responses were recorded from the right first dorsal interosseous muscle (FDI) in several different stimulation conditions. We gave both monophasic and biphasic rTMS over the motor cortex at a frequency of 0.5, 1, 2 or 3Hz. To study excitability changes of the spinal cord, we also performed 3Hz rTMS at the foramen magnum level [Ugawa Y, Uesaka Y, Terao Y, Hanajima R, Kanazawa I. Magnetic stimulation of corticospinal pathways at the foramen magnum level in humans. Ann Neurol 1994;36:618-24]. We measured the size and latency of each of 20 MEPs recorded in the different stimulation conditions. 2 or 3Hz stimulation with either monophasic or biphasic pulses evoked MEPs that gradually increased in amplitude with the later MEPs being significantly larger than the earlier ones. Monophasic rTMS showed much more facilitation than biphasic stimulation, particularly at 3Hz. Stimulation at the foramen magnum level at 3Hz elicited fairly constant MEPs. The enhancement of cortical MEPs with no changes of responses to foramen magnum level stimulation suggests that the facilitation occurred at the motor cortex. We hypothesize that monophasic TMS has a stronger short-term effect during repetitive stimulation than biphasic TMS because monophasic pulses preferentially activate one population of neurons oriented in the same direction so that their effects readily summate. Biphasic pulses in contrast may activate several different populations of neurons (both facilitatory and inhibitory) so that summation of the effects is not so clear as with monophasic pulses. When single stimuli are applied, however, biphasic TMS is thought to be more powerful than monophasic TMS because the peak-to-peak amplitude of stimulus pulse is higher and its duration is longer when the same intensity of stimulation (the same amount of current is stored by the stimulator) is used. This means that when using rTMS as a therapeutic tool or in research fields, the difference in waveforms of magnetic pulses (monophasic or biphasic) may affect the results.
Article
Specific stimulation of neuronal circuits may promote selective inhibition or facilitation of corticospinal tract excitability. Monophasic stimulation is more likely to achieve direction-specific neuronal excitation. In 10 healthy subjects, we compared four types of repetitive transcranial magnetic stimulation (rTMS), monophasic and biphasic stimuli with the initial current in the brain flowing antero-posteriorly ("posteriorly directed") or postero-anteriorly ("anteriorly directed"). We applied rTMS over the primary motor cortex contralateral to the dominant hand, using 80 stimuli at 5 Hz frequency at an intensity yielding baseline motor evoked potential (MEP) amplitudes of 1 mV. Monophasic stimulation was always more efficient than biphasic. Facilitation was induced by intracerebral anteriorly directed current flow and inhibition by posteriorly oriented current flow, although only initially for approximately 30 pulses. The early inhibition was absent when studied during a tonic muscle contraction. Several mechanisms could account for these findings. They include a more efficient excitation of inhibiting circuits by posteriorly oriented pulses, and a back-propagating D-wave inhibiting early I-waves and thus inducing early inhibition of MEP amplitude. In any case biphasic rTMS results can be explained by a mixture of monophasic opposite stimulations. We propose the use of monophasic pulses for maximizing effects during rTMS.
Article
To compare half sine transcranial magnetic stimuli (TMS) with conventional monophasic and biphasic stimuli, measuring resting and active motor threshold, motor evoked potential (MEP) input/output curve, MEP latency, and silent period duration. We stimulated the dominant hand representation of the motor cortex in 12 healthy subjects utilising two different MagPro stimulators to generate TMS pulses of distinct monophasic, half sine and biphasic shape with anteriorly or posteriorly directed current flow. The markedly asymmetric monophasic pulse with a posterior current flow in the brain yielded a higher motor threshold, a less steep MEP input/output curve and a longer latency than all other TMS types. Similar but less pronounced results were obtained with a less asymmetric half sine pulses. The biphasic stimuli yielded the lowest motor threshold and a short latency, particularly with the posterior current direction. The more asymmetric the monophasic pulse, the stronger the difference to biphasic pulses. The 3rd and 4th quarter cycle of the biphasic waveform make it longer than any other waveform studied here and likely contribute to lowering motor threshold, shortening MEP latency and reversing the influence of current direction. This systematic comparison of 3 waveforms and two current directions allows a better understanding of the mechanisms of TMS.
Article
Optimising stimulus parameters is important in maximising the efficacy of repetitive transcranial magnetic stimulation (rTMS) in treatment applications. RTMS over motor cortex has been reported as more effective in producing corticospinal inhibition when a monophasic rather than a biphasic stimulus waveform is used. However, non-optimal coil orientation and high intensities of monophasic rTMS may have influenced previous results. In eight healthy subjects, we measured motor evoked potentials (MEPs) in a hand muscle after monophasic and biphasic rTMS (1 Hz for 15 min) over the motor cortex with the coil always in the optimal orientation. MEPs were evoked by both monophasic and biphasic stimuli. MEPs were initially significantly reduced after monophasic but not biphasic rTMS. However, a late reduction was seen after biphasic rTMS. These motor cortical findings may not be directly applicable to prefrontal rTMS. This study confirms that low frequency rTMS with monophasic pulses produces more corticospinal inhibition than with biphasic pulses, even when the direction of current and intensity are as well-matched as possible.
Article
We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.
Article
To study differences in the long-term after-effect between high-frequency, monophasic and biphasic repetitive transcranial magnetic stimulation (rTMS). Ten hertz rTMS was delivered over the left primary motor cortex and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. To probe motor cortex excitability we recorded MEPs at several timings before, during and after several types of conditioning rTMSs. We also recorded F-waves to probe spinal excitability changes. Thousand pulses were given in total, with a train of 10 Hz, 100 pulses delivered every minute (ten trains for 10min). The intensity was fixed at 90% active motor threshold (AMT) or 90% resting motor threshold (RMT) for both monophasic and biphasic rTMS. In addition, we performed a monophasic rTMS experiment using a fixed intensity of 90% RMT for biphasic pulses. At 90% AMT, MEPs were enhanced for a few minutes after both monophasic and biphasic rTMS. On the other hand, at 90% RMT, a larger and longer enhancement of MEPs was evoked after monophasic rTMS than after biphasic rTMS. Monophasic rTMS at an intensity adjusted to biphasic 90% RMT elicited a great enhancement similar to that after monophasic rTMS at monophasic 90% RMT. Neither F-wave amplitude nor its occurrence rate was significantly altered by 90% RMT monophasic rTMS. These results suggest that enhancement after rTMS occurs at the motor cortex. Monophasic rTMS has a stronger after-effect on motor cortical excitability than biphasic rTMS. This is probably because monophasic pulses preferentially activate a relatively uniform population of neurons oriented in the same direction and their effects summate more readily than biphasic rTMS activating differently oriented neurons at slight different timings altogether. The present results suggest that when using rTMS as a therapeutic tool or in research fields, the waveforms of magnetic pulses may affect the results profoundly.
Conference Paper
The authors present measured turn-off losses in IGBTs (insulated-gate bipolar transistors) from six different manufacturers. The rated breakdown-voltage and on-state current are 600 V and 75 A, respectively, for all transistors tested, except the IR-transistor which has 55 A as rate current. Hard switching and switching with a capacitive turn-off snubber are analyzed, both at 25 degrees C and 125 degrees C. The influence of variations in the gate resistance is covered. Conclusions from a similar set of measurements on 1000-1200 V IGBTs are also given. The loss reduction when using a turn-off snubber is larger than expected from experience with bipolar junction transistors. This is mainly due to the fact that the first part of the current fall time until the current tail is reached is shorter when a capacitive snubber is used than in hard switching. The turn-off losses increase strongly with temperature and also with the transistor current at turn-off. There is a significant increase in turn-off losses with increasing gate resistance.< >
Article
The turn-off of IGBTs in hard- and soft-switching converters is analyzed using nonquasi-static analysis. It is shown that while the turn-off current waveform for hard-switching is governed solely by the device for a particular value of on-state current and bus voltage, turn-off current waveform for soft-switching is strongly dependent on device-circuit interactions, so that a trade-off between turn-off loss and switching time can be made using external circuit elements. Models are developed to explain IGBT turn-off for both hard- and soft-switching conditions. Hard-switching considers both inductive and resistive loads. Calculated results are validated by comparison with results of measurements and two-dimensional (2-D) numerical simulations
Article
A novel transcranial magnetic stimulation (TMS) device with controllable pulse width (PW) and near-rectangular pulse shape (cTMS) is described. The cTMS device uses an insulated gate bipolar transistor (IGBT) with appropriate snubbers to switch coil currents up to 6 kA, enabling PW control from 5 mus to over 100 mus. The near-rectangular induced electric field pulses use 2%-34% less energy and generate 67%-72% less coil heating compared to matched conventional cosine pulses. CTMS is used to stimulate rhesus monkey motor cortex in vivo with PWs of 20 to 100 mus, demonstrating the expected decrease of threshold pulse amplitude with increasing PW. The technological solutions used in the cTMS prototype can expand functionality, and reduce power consumption and coil heating in TMS, enhancing its research and therapeutic applications.
Principles of magnetic stimulator design Handbook of Transcranial Magnetic Stimulation ed A Pascual-Leone
  • R Jalinous
  • Davey
  • E Rothwell
  • B Wassermann
  • Puri
Jalinous R 2002 Principles of magnetic stimulator design Handbook of Transcranial Magnetic Stimulation ed A Pascual-Leone, N J Davey, J Rothwell, E M Wassermann and B K Puri (London: Arnold) pp 30–8
Snubber Circuits for Power Electronics. SMPS Technology
  • R Severns
Severns, R. Snubber Circuits for Power Electronics. SMPS Technology. 2008. [E-book] Available: http://www.snubberdesign.com/snubber-book.html
Snubber Circuits for Power Electronics SMPS Technology [E-book] Available at www
  • R Severns
Pulse configuration-dependent effects of repetitive transcranial magnetic stimulation on visual perception
  • A Antal
  • T Z Kincses
  • M A Nitsche
  • O Bartfai
  • I Demmer
  • M Sommer
  • W Paulus
Handbook of Transcranial Magnetic Stimulation
  • R Jalinous
  • A Pascual-Leone
  • N J Davey
  • J Rothwell
  • E M Wassermann
  • B K Puri
Jalinous, R. Principles of magnetic stimulator design. In: Pascual-Leone, A.; Davey, NJ.; Rothwell, J.; Wassermann, EM.; Puri, BK., editors. Handbook of Transcranial Magnetic Stimulation. Arnold; London: 2002. p. 30-38.
Magstim coils & accessories: operating manual 1623-23-06
  • Magstim Co