Numerical modelling of plasticity induced by Quadri-pulse stimulation

Quadri-pulse stimulation (QPS), a type of repetitive transcranial magnetic stimulation (rTMS), can induce a considerable aftereffect on cortical synapses. Human experiments have shown that the type of effect on synaptic efficiency (in terms of potentiation or depression) depends on the time interval between pulses. The maturation of biophysically-based models, which describe the physiological properties of plasticity mathematically, offers a beneficial framework to explore induced plasticity for new stimulation protocols. To model the QPS paradigm, a phenomenological model based on the knowledge of spike timing-dependent plasticity (STDP) mechanisms of synaptic plasticity was utilized where the cortex builds upon the platform of neuronal population modeling. Induced cortical plasticity was modeled for both conventional monophasic pulses and unidirectional pulses generated by the cTMS device, in a total of 117 different scenarios. For the conventional monophasic stimuli, the results of the predictive model broadly follow what is typically seen in human experiments. Unidirectional pulses can produce a similar range of plasticity. Additionally, changing the pulse width had a considerable effect on the plasticity (approximately 20% increase). As the width of the positive phase increases, the size of the potentiation will also increase. The proposed model can generate predictions to guide future plasticity experiments. Estimating the plasticity and optimizing the rTMS protocols might effectively improve the safety implications of TMS experiments by reducing the number of delivered pulses to participants. Finding the optimal stimulation protocol with the maximum potentiation/depression can lead to the design of a new TMS pulse generator device with targeted hardware and control algorithms

The sensitivity of ECG contamination to surgical implantation site in brain computer interfaces.

BACKGROUND Brain sensing devices are approved today for Parkinson's, essential tremor, and epilepsy therapies. Clinical decisions for implants are often influenced by the premise that patients will benefit from using sensing technology. However, artifacts, such as ECG contamination, can render such treatments unreliable. Therefore, clinicians need to understand how surgical decisions may affect artifact probability. OBJECTIVES Investigate neural signal contamination with ECG activity in sensing enabled neurostimulation systems, and in particular clinical choices such as implant location that impact signal fidelity. METHODS Electric field modeling and empirical signals from 85 patients were used to investigate the relationship between implant location and ECG contamination. RESULTS The impact on neural recordings depends on the difference between ECG signal and noise floor of the electrophysiological recording. Empirically, we demonstrate that severe ECG contamination was more than 3.2x higher in left-sided subclavicular implants (48.3%), when compared to right-sided implants (15.3%). Cranial implants did not show ECG contamination. CONCLUSIONS Given the relative frequency of corrupted neural signals, we conclude that implant location will impact the ability of brain sensing devices to be used for "closed-loop" algorithms. Clinical adjustments such as implant location can significantly affect signal integrity and need consideration

A neurostimulator system for real, sham, and multi-target transcranial magnetic stimulation

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

Comparison between the modelled response of primary motor cortex neurons to pulse-width modulated and conventional TMS stimuli

In this study, the neural response to pulse-width modulated (PWM) transcranial magnetic stimulation (TMS) is estimated using a computational neural model which simulates the response of cortical neurons to TMS. The recently introduced programmable TMS uses PWM to approximate conventional resonance-based TMS pulses by fast switching between voltage levels. The effect of such stimulation on the six cortical layers is modelled by estimating the activation threshold of the neurons. Modelling results are compared between the novel device and that of conventional TMS stimuli generated by Magstim stimulators. The neural responses to the PWM pulses and the conventional stimuli show a high correlation, which validates the use of pulse-width modulated pulses in TMS.Clinical Relevance— This computational modelling study demonstrates an equivalent effect of PWM and conventional TMS pulses on the nervous system which paves the way to more flexibility in exploring and choosing stimulation parameters for TMS treatment

xTMS: A pulse generator for exploring transcranial magnetic stimulation therapies

A cascaded H-bridge based pulse generator for transcranial magnetic stimulation is introduced. The system demonstrates complete flexibility for producing different shape, duration, direction, and rate of repetition of stimulus pulses within its electrical limits, and can emulate all commercial and research systems available to-date in this application space. An offline model predictive control algorithm, used to generate pulses and sequences, shows superior performance compared to conventional carrier-based pulse width modulation. A fully functioning laboratory prototype delivers up to 1.5 kV, 6 kA pulses, and is ready to be used as a research tool for the exploration of transcranial magnetic stimulation therapies by leveraging the many degrees-of-freedom offered by the design

EMG data and scripts for: The effect of pulse shape in theta-burst stimulation: monophasic vs biphasic TMS

Method of data collection: The TMS coil was positioned over the left primary motor cortex and oriented at 45º to the midline with the handle pointing posteriorly. EMG was recorded from the FDI of the right hand by positioning disposable neonatal ECG electrodes in a belly-tendon montage, with the ground electrode over the ulnar styloid process. Two baseline blocks of MEPs were recorded 5 minutes apart (30 pulses per block). iTBS was applied 10 minutes after the start of the first baseline block and follow-up blocks were recorded every 5-10 minutes after the start of the iTBS protocol over the following hour (at 5, 10, 15, 20, 30, 40, 50 and 60 min). For each participant, two sessions were M1 conditions, where iTBS was applied to the motor hotspot, and one session was a control condition, where iTBS was applied to the vertex (indicated as 'sham' in the data). Data description: The data includes the baseline and post-iTBS EMG measurements from healthy participants, when applying pulses at 120% of the resting motor threshold (RMT) using a Magstim 200. Each data collection session has its own folder, named by individual participants indicated with the letter S followed by a number and the session number. Each folder contains the EMG data in a csv file, the RMT and stimulation conditions in separate Text files. The provided scripts load in the data, compute the analysis and generate the figures corresponding to the published paper

Design analysis and circuit topology optimization for programmable magnetic neurostimulator

Transcranial magnetic stimulation (TMS) is a form of non-invasive brain stimulation commonly used to modulate neural activity. Despite three decades of examination, the generation of flexible magnetic pulses is still a challenging technical question. It has been revealed that the characteristics of pulses influence the bio-physiology of neuromodulation. In this study, a second-generation programmable TMS (xTMS) equipment with advanced stimulus shaping is introduced that uses cascaded H-bridge inverters and a phase-shifted pulse-width modulation (PWM). A low-pass RC filter model is used to estimate stimulated neural behavior, which helps to design the magnetic pulse generator, according to neural dynamics. The proposed device can generate highly adjustable magnetic pulses, in terms of waveform, polarity and pattern. We present experimental measurements of different stimuli waveforms, such as monophasic, biphasic and polyphasic shapes with peak coil current and the delivered energy of up to 6 kA and 250 J, respectively. The modular and scalable design idea presented here is a potential solution for generating arbitrary and highly customizable magnetic pulses and transferring repetitive paradigms