Single pointwise samples of electric field on a neuron model cannot predict activation threshold by brain stimulation.

Background: Some computational models of neural activation by transcranial magnetic stimulation overestimate the electric field (E-field) threshold compared to in vivo measurements. A recent study proposed a statistical method to account for the influence of microscopic perturbations to the E-field. The method, however, relies on the unsubstantiated assumption that thresholds can be predicted by single pointwise samples of the E-field strength along neural cables.

Stochastic Approximator of Motor Threshold (SAMT) for Transcranial Magnetic Stimulation: Online Software and Its Performance in Clinical Studies.

Background: The motor threshold (MT) plays a central role in probing brain excitability and individualizing transcranial magnetic stimulation (TMS). Previously, we proposed stochastic approximation (SA) as a new method for determining TMS MT and demonstrated its excellent speed and accuracy via simulations. SA also has low computational requirements and is robust to potential model flaws.

Role of frequency-dependent and capacitive tissue properties in spinal cord stimulation models.

Spinal cord stimulation (SCS) models simulate the electric fields (-fields) generated in targeted tissues, which in turn govern physiological and then behavioral outcomes. Notwithstanding increasing sophistication and adoption in therapy optimization, SCS models typically calculate-fields using quasi-static approximation (QSA). QSA, as implemented in neuromodulation models, neglects the frequency-dependent tissue conductivity (dispersion), as well as propagation, capacitive, and inductive effects on the-field.

Rethinking noise floor characterisation in motor-evoked potentials.

. Motor-evoked potentials (MEPs) in response to brain stimulation, such as transcranial magnetic stimulation (TMS), allow quantification of corticospinal excitability and have served in the design of almost all available neuromodulatory interventions. So-called thresholding of MEPs at a point not too far above the noise floor establishes the reference point for dosage and safety.

Bridging macroscopic and microscopic modeling of electric field by brain stimulation.

Background: Modeling the electric field (E-field) on the microscopic scale improves our understanding of brain stimulation modalities and modeling methods but requires careful consideration of the conductivity values and correction of the field amplitudes to match conventional models on the macroscopic scale.

Objective: We analyze the correction step and discuss its relevance and implications for E-field modeling efforts bridging the macroscopic and microscopic scales.

Methods: We provide the theoretical framework for comparing microscopic and macroscopic models and describe approaches for effectively and efficiently matching the E-field amplitude and tissue conductivity.

Guidance for sharing computational models of neural stimulation: from project planning to publication.

. Sharing computational models offers many benefits, including increased scientific rigor during project execution, readership of the associated paper, resource usage efficiency, replicability, and reusability. In recognition of the growing practice and requirement of sharing models, code, and data, herein, we provide guidance to facilitate sharing of computational models by providing an accessible resource for regular reference throughout a project's stages.

Modulation-Enhanced Nearest-Level Quantization for a Wide Output Bandwidth.

Multilevel converters have enabled various applications that are not possible with conventional two-level converters. Many of these applications, however, need a high output bandwidth, often approaching the switching rate limit of the transistors, with high quality, e.g.

Quasistatic approximation in neuromodulation.

We define and explain the quasistatic approximation (QSA) as applied to field modeling for electrical and magnetic stimulation. Neuromodulation analysis pipelines include discrete stages, and QSA is applied specifically when calculating the electric and magnetic fields generated in tissues by a given stimulation dose. QSA simplifies the modeling equations to support tractable analysis, enhanced understanding, and computational efficiency.

Quasistatic approximation in neuromodulation.

We define and explain the quasistatic approximation (QSA) as applied to field modeling for electrical and magnetic stimulation. Neuromodulation analysis pipelines include discrete stages, and QSA is applied specifically when calculating the electric and magnetic fields generated in tissues by a given stimulation dose. QSA simplifies the modeling equations to support tractable analysis, enhanced understanding, and computational efficiency.

Three novel methods for determining motor threshold with transcranial magnetic stimulation outperform conventional procedures.

. Thresholding of neural responses is central to many applications of transcranial magnetic stimulation (TMS), but the stochastic aspect of neuronal activity and motor evoked potentials (MEPs) challenges thresholding techniques. We analyzed existing methods for obtaining TMS motor threshold and their variations, introduced new methods from other fields, and compared their accuracy and speed.

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

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.A two-step optimization method was developed that uses the temporal relationship between the electric field (E-field) and coil current waveforms.

Responses of model cortical neurons to temporal interference stimulation and related transcranial alternating current stimulation modalities.

Temporal interference stimulation (TIS) was proposed as a non-invasive, focal, and steerable deep brain stimulation method. However, the mechanisms underlying experimentally-observed suprathreshold TIS effects are unknown, and prior simulation studies had limitations in the representations of the TIS electric field (E-field) and cerebral neurons. We examined the E-field and neural response characteristics for TIS and related transcranial alternating current stimulation modalities.

Subsecond multichannel magnetic control of select neural circuits in freely moving flies.

Precisely timed activation of genetically targeted cells is a powerful tool for the study of neural circuits and control of cell-based therapies. Magnetic control of cell activity, or 'magnetogenetics', using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and freely behaving animal studies. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents precise temporal modulation of neural activity.

Isolating two sources of variability of subcortical stimulation to quantify fluctuations of corticospinal tract excitability.

Objective: Investigate the variability previously found with cortical stimulation and handheld transcranial magnetic stimulation (TMS) coils, criticized for its high potential of coil position fluctuations, bypassing the cortex using deep brain electrical stimulation (DBS) of the corticospinal tract with fixed electrodes where both latent variations of the coil position of TMS are eliminated and cortical excitation fluctuations should be absent.

Methods: Ten input-output curves were recorded from five anesthetized cats with implanted DBS electrodes targeting the corticospinal tract. Goodness of fit of regressions with a conventional single variability source as well as a dual variability source model was quantified using a Schwarz Bayesian Information approach to avoid overfitting.

A wireless millimetric magnetoelectric implant for the endovascular stimulation of peripheral nerves.

Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries.

Multichannel power electronics and magnetic nanoparticles for selective thermal magnetogenetics.

We present a combination of a power electronics system and magnetic nanoparticles that enable frequency-multiplexed magnetothermal-neurostimulation with rapid channel switching between three independent channels spanning a wide frequency range.The electronics system generates alternating magnetic field spanning 50 kHz to 5 MHz in the same coil by combining silicon (Si) and gallium-nitride (GaN) transistors to resolve the high spread of coil impedance and current required throughout the wide bandwidth. The system drives a liquid-cooled field coil via capacitor banks, forming three series resonance channels which are multiplexed using high-voltage contactors.

Simulation of transcranial magnetic stimulation in head model with morphologically-realistic cortical neurons.

Background: Transcranial magnetic stimulation (TMS) enables non-invasive modulation of brain activity with both clinical and research applications, but fundamental questions remain about the neural types and elements TMS activates and how stimulation parameters affect the neural response.

Objective: To develop a multi-scale computational model to quantify the effect of TMS parameters on the direct response of individual neurons.

Methods: We integrated morphologically-realistic neuronal models with TMS-induced electric fields computed in a finite element model of a human head to quantify the cortical response to TMS with several combinations of pulse waveforms and current directions.

Coupling Magnetically Induced Electric Fields to Neurons: Longitudinal and Transverse Activation.

We present a theory and computational models to couple the electric field induced by magnetic stimulation to neuronal membranes. Based on the characteristics of magnetically induced electric fields and the modified cable equation that we developed previously, quasipotentials are derived as a simple and accurate approximation for coupling of the electric fields to neurons. The conventional and modified cable equations are used to simulate magnetic stimulation of long peripheral nerves by circular and figure-8 coils.

Modified cable equation incorporating transverse polarization of neuronal membranes for accurate coupling of electric fields.

Objective: We present a theory and computational methods to incorporate transverse polarization of neuronal membranes into the cable equation to account for the secondary electric field generated by the membrane in response to transverse electric fields. The effect of transverse polarization on nonlinear neuronal activation thresholds is quantified and discussed in the context of previous studies using linear membrane models.

Approach: The response of neuronal membranes to applied electric fields is derived under two time scales and a unified solution of transverse polarization is given for spherical and cylindrical cell geometries.

Redesigning existing transcranial magnetic stimulation coils to reduce energy: application to low field magnetic stimulation.

Objective: To present a systematic framework and exemplar for the development of a compact and energy-efficient coil that replicates the electric field (E-field) distribution induced by an existing transcranial magnetic stimulation coil.

Approach: The E-field generated by a conventional low field magnetic stimulation (LFMS) coil was measured for a spherical head model and simulated in both spherical and realistic head models. Then, using a spherical head model and spatial harmonic decomposition, a spherical-shaped cap coil was synthesized such that its windings conformed to a spherical surface and replicated the E-field on the cortical surface while requiring less energy.