Modular pulse synthesizer for transcranial magnetic stimulation with fully adjustable pulse shape and sequence

Abstract

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.

Optimisation of asymmetric field pulses for transcranial magnetic stimulation

“…These results would be consistent with the idea that different current directions recruit distinct sets of excitatory synaptic inputs to corticospinal neurons (Di Lazzaro and Rothwell 2014). Moreover, TMS devices with adjustable waveforms have enabled the synthesis of a wide range of either rectangular field pulses with adjustable pulse duration, widths, and polarities (cTMS) or relatively freely designed pulses (modular pulse synthesizers) (Goetz et al 2012a;Li et al 2022;Peterchev et al 2011;Zeng et al 2022). Therefore, further optimisation of the asymmetric field pulse enhance its selectivity and efficacy in targeting specific neural populations, which could have important implications for future TMS applications.…”

Optimized monophasic pulses with equivalent electric field for rapid-rate transcranial magnetic stimulation

“…A modular pulse synthesizer TMS (MPS-TMS) device with six modules [41] was used to generate the optimized pulses. All waveforms were normalized to the maximum peak value and interpolated using a 5 MHz sampling rate.…”

“…Several TMS technologies allow increased waveform flexibility [38][39][40][41][42][43][44][45], but pulse shapes that are both highly efficient with low coil heating and replicate accurately the E-field waveform of monophasic pulses have not been implemented. Herein we design pulse shapes that produce estimated neural activation equivalent to conventional monophasic pulses by matching the induced E-field but with minimized pulse power and coil heating.…”

xTMS: A Pulse Generator for Exploring Transcranial Magnetic Stimulation Therapies

“…The simplicity offered by the MMCs is, however, often complicated in their reported applications in TMS. For example, an obvious compromise in [ 14 ] is the paralleling of the dc-link capacitors of two or more H-bridges to generate a lower intensity output pulse, which might otherwise be achieved by improved modulation. To connect the capacitors in parallel, their voltages must be balanced using complex control [ 15 ].…”