Reduced Auditory Perception and Brain Response with Quiet TMS Coil.

BACKGROUND: Electromagnetic forces in transcranial magnetic stimulation (TMS) coils generate a loud clicking sound that produces confounding auditory activation and is potentially hazardous to hearing. To reduce this noise while maintaining stimulation efficiency similar to conventional TMS coils, we previously developed a quiet TMS double containment coil (qTMS-DCC). OBJECTIVE: To compare the stimulation strength, perceived loudness, and EEG response between qTMS-DCC and a commercial TMS coil. METHODS: Nine healthy volunteers participated in a within-subject study design. The resting motor thresholds (RMTs) for qTMS-DCC and MagVenture Cool-B65 were measured. Psychoacoustic titration matched the Cool-B65 loudness to qTMS-DCC pulsed at 80, 100, and 120% RMT. Event-related potentials (ERPs) were recorded for both coils. The psychoacoustic titration and ERPs were acquired with the coils both on and 6 cm off the scalp, the latter isolating the effects of airborne auditory stimulation from body sound and electromagnetic stimulation. The ERP comparisons focused on a centro-frontal region that encompassed peak responses in the global signal. RESULTS: RMT did not differ significantly between the coils, with or without the EEG cap on the head. qTMS-DCC was perceived to be substantially quieter than Cool-B65. For example, qTMS-DCC at 100% coil-specific RMT sounded like Cool-B65 at 34% RMT. The general ERP waveform and topography were similar between the two coils, as were early-latency components, indicating comparable electromagnetic brain stimulation in the on-scalp condition. qTMS-DCC had a significantly smaller P180 component in both on-scalp and off-scalp conditions, supporting reduced auditory activation. CONCLUSIONS: The stimulation efficiency of qTMS-DCC matched Cool-B65, while having substantially lower perceived loudness and auditory-evoked potentials. Highlights: qTMS coil is subjectively and objectively quieter than conventional Cool-B65 coilqTMS coil at 100% motor threshold was as loud as Cool-B65 at 34% motor thresholdAttenuated coil noise reduced auditory N100 and P180 evoked response componentsqTMS coil enables reduction of auditory activation without masking.

An optically pumped magnetic gradiometer for the detection of human biomagnetism.

We realise an intrinsic optically pumped magnetic gradiometer based on non-linear magneto-optical rotation. We show that our sensor can reach a gradiometric sensitivity of 18 fT cm-1Hz-1 and can reject common mode homogeneous magnetic field noise with up to 30 dB attenuation. We demonstrate that our magnetic field gradiometer is sufficiently sensitive and resilient to be employed in biomagnetic applications. In particular, we are able to record the auditory evoked response of the human brain, and to perform real-time magnetocardiography in the presence of external magnetic field disturbances. Our gradiometer provides complementary capabilities in human biomagnetic sensing to optically pumped magnetometers, and opens new avenues in the detection of human biomagnetism.

Transcranial magnetic stimulation input-output curve slope differences suggest variation in recruitment across muscle representations in primary motor cortex.

Measurement of the input-output (IO) curves of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) can be used to assess corticospinal excitability and motor recruitment. While IO curves have been used to study disease and pharmacology, few studies have compared the IO curves across the body. This study sought to characterize IO curve parameters across the dominant and non-dominant sides of upper and lower limbs in healthy participants. Laterality preferences were assessed in eight healthy participants and IO curves were measured bilaterally for the first dorsal interosseous (FDI), biceps brachii (BB), and tibialis anterior (TA) muscles. Results show that FDI has lower motor threshold than BB which is, in turn, lower than TA. In addition, both BB and TA have markedly shallower logarithmic IO curve slopes from small to large MEP responses than FDI. After normalizing these slopes by their midpoints to account for differences in motor thresholds, which could result from geometric factors such as the target depth, large differences in logarithmic slopes remain present between all three muscles. The differences in slopes between the muscles could not be explained by differences in normalized IO curve spreads, which relate to the extent of the cortical representation and were comparable across the muscles. The IO curve differences therefore suggest muscle-dependent variations in TMS-evoked recruitment across the primary motor cortex, which should be considered when utilizing TMS-evoked MEPs to study disease states and treatment effects.

Advanced Pipeline for Designing Multi-Locus TMS Coils With Current Density Constraints.

OBJECTIVE: This work aims for a method to design manufacturable windings for transcranial magnetic stimulation (TMS) coils with fine control over the induced electric field (E-field) distributions. Such TMS coils are required for multi-locus TMS (mTMS). METHODS: We introduce a new mTMS coil design workflow with increased flexibility in target E-field definition and faster computations compared to our previous method. We also incorporate custom current density and E-field fidelity constraints to ensure that the target E-fields are accurately reproduced with feasible winding densities in the resulting coil designs. We validated the method by designing, manufacturing, and characterizing a 2-coil mTMS transducer for focal rat brain stimulation. RESULTS: Applying the constraints reduced the computed maximum surface current densities from 15.4 and 6.6 kA/mm to the target value 4.7 kA/mm, yielding winding paths suitable for a 1.5-mm-diameter wire with 7-kA maximum currents while still replicating the target E-fields with the predefined 2.8% maximum error in the FOV. The optimization time was reduced by two thirds compared to our previous method. CONCLUSION: The developed method allowed us to design a manufacturable, focal 2-coil mTMS transducer for rat TMS impossible to attain with our previous design workflow. SIGNIFICANCE: The presented workflow enables considerably faster design and manufacturing of previously unattainable mTMS transducers with increased control over the induced E-field distribution and winding density, opening new possibilities for brain research and clinical TMS.

Optimising the sensing volume of OPM sensors for MEG source reconstruction.

Magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) has been hailed as the future of electrophysiological recordings from the human brain. In this work, we investigate how the dimensions of the sensing volume (the vapour cell) affect the performance of both a single OPM-MEG sensor and a multi-sensor OPM-MEG system. We consider a realistic noise model that accounts for background brain activity and residual noise. By using source reconstruction metrics such as localization accuracy and time-course reconstruction accuracy, we demonstrate that the best overall sensitivity and reconstruction accuracy are achieved with cells that are significantly longer and wider that those of the majority of current commercial OPM sensors. Our work provides useful tools to optimise the cell dimensions of OPM sensors in a wide range of environments.

Transcranial magnetic stimulation set-up for small animals.

Transcranial magnetic stimulation (TMS) is widely applied on humans for research and clinical purposes. TMS studies on small animals, e.g., rodents, can provide valuable knowledge of the underlying neurophysiological mechanisms. Administering TMS on small animals is, however, prone to technical difficulties, mainly due to their small head size. In this study, we aimed to develop an energy-efficient coil and a compatible experimental set-up for administering TMS on rodents. We applied a convex optimization process to develop a minimum-energy coil for TMS on rats. As the coil windings of the optimized coil extend to a wide region, we designed and manufactured a holder on which the rat lies upside down, with its head supported by the coil. We used the set-up to record TMS-electromyography, with electromyography recorded from limb muscles with intramuscular electrodes. The upside-down placement of the rat allowed the operator to easily navigate the TMS without the coil blocking their field of view. With this paradigm, we obtained consistent motor evoked potentials from all tested animals.

Modular multilevel TMS device with wide output range and ultrabrief pulse capability for sound reduction.

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 (>8.25µs 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.

TMS with fast and accurate electronic control: Measuring the orientation sensitivity of corticomotor pathways.

BACKGROUND: Transcranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing. OBJECTIVE: We aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability. METHODS: We designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custom-made electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3° steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude. RESULTS: The two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity. CONCLUSION: The developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols.

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation.

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.

Double-Containment Coil With Enhanced Winding Mounting for Transcranial Magnetic Stimulation With Reduced Acoustic Noise.

OBJECTIVE: This work aims to reduce the acoustic noise level of transcranial magnetic stimulation (TMS) coils. TMS requires high currents (several thousand amperes) to be pulsed through the coil, which generates a loud acoustic impulse whose peak sound pressure level (SPL) can exceed 130 dB(Z). This sound poses a risk to hearing and elicits unwanted neural activation of auditory brain circuits. METHODS: We propose a new double-containment coil with enhanced winding mounting (DCC), which utilizes acoustic impedance mismatch to contain and dissipate the impulsive sound within an air-tight outer casing. The coil winding is potted into a rigid block, which is mounted to the outer casing through the block´s acoustic nodes that are subject to minimum vibration during the pulse. The rest of the winding block is isolated from the casing by an air gap, and the sound is absorbed by polyester fiber panels within the casing. The casing thickness under the winding center is minimized to maximize the electric field output. RESULTS: Compared to commercial figure-of-eight TMS coils, the DCC prototype has 18-41 dB(Z) lower peak SPL at matched stimulation strength, whilst providing 28% higher maximum stimulation strength than equally focal coils. CONCLUSION: The DCC design greatly reduces the acoustic noise of TMS while increasing the achievable stimulation strength. SIGNIFICANCE: The acoustic noise reduction from our coil design is comparable to that provided by typical hearing protection devices. This coil design approach can enhance hearing safety and reduce auditory co-activations in the brain and other detrimental effects of TMS sound.

Individual head models for estimating the TMS-induced electric field in rat brain.

In transcranial magnetic stimulation (TMS), the initial cortical activation due to stimulation is determined by the state of the brain and the magnitude, waveform, and direction of the induced electric field (E-field) in the cortex. The E-field distribution depends on the conductivity geometry of the head. The effects of deviations from a spherically symmetric conductivity profile have been studied in detail in humans. In small mammals, such as rats, these effects are more pronounced due to their less spherical head, proportionally much thicker neck region, and overall much smaller size compared to the TMS coils. In this study, we describe a simple method for building individual realistically shaped head models for rats from high-resolution X-ray tomography images. We computed the TMS-induced E-field with the boundary element method and assessed the effect of head-model simplifications on the estimated E-field. The deviations from spherical symmetry have large, non-trivial effects on the E-field distribution: for some coil orientations, the strongest stimulation is in the brainstem even when the coil is over the motor cortex. With modelling prior to an experiment, such problematic coil orientations can be avoided for more accurate targeting.

Sound comparison of seven TMS coils at matched stimulation strength.

BACKGROUND: Accurate data on the sound emitted by transcranial magnetic stimulation (TMS) coils is lacking. METHODS: We recorded the sound waveforms of seven coils with high bandwidth. We estimated the neural stimulation strength by measuring the induced electric field and applying a strength-duration model to account for different waveforms. RESULTS: Across coils, at maximum stimulator output and 25 cm distance, the sound pressure level (SPL) was 98-125 dB(Z) per pulse and 76-98 dB(A) for a 20 Hz pulse train. At 5 cm distance, these values were estimated to increase to 112-139 dB(Z) and 90-112 dB(A), respectively. CONCLUSIONS: The coils' airborne sound can exceed some exposure limits for TMS subjects and, in some cases, for operators. These findings are consistent with the current TMS safety guidelines that recommend the use of hearing protection.

Conditions for numerically accurate TMS electric field simulation.

BACKGROUND: Computational simulations of the E-field induced by transcranial magnetic stimulation (TMS) are increasingly used to understand its mechanisms and to inform its administration. However, characterization of the accuracy of the simulation methods and the factors that affect it is lacking. OBJECTIVE: To ensure the accuracy of TMS E-field simulations, we systematically quantify their numerical error and provide guidelines for their setup. METHOD: We benchmark the accuracy of computational approaches that are commonly used for TMS E-field simulations, including the finite element method (FEM) with and without superconvergent patch recovery (SPR), boundary element method (BEM), finite difference method (FDM), and coil modeling methods. RESULTS: To achieve cortical E-field error levels below 2%, the commonly used FDM and 1st order FEM require meshes with an average edge length below 0.4 mm, 1st order SPR-FEM requires edge lengths below 0.8 mm, and BEM and 2nd (or higher) order FEM require edge lengths below 2.9 mm. Coil models employing magnetic and current dipoles require at least 200 and 3000 dipoles, respectively. For thick solid-conductor coils and frequencies above 3 kHz, winding eddy currents may have to be modeled. CONCLUSION: BEM, FDM, and FEM all converge to the same solution. Compared to the common FDM and 1st order FEM approaches, BEM and 2nd (or higher) order FEM require significantly lower mesh densities to achieve the same error level. In some cases, coil winding eddy-currents must be modeled. Both electric current dipole and magnetic dipole models of the coil current can be accurate with sufficiently fine discretization.

Short-interval intracortical inhibition in human primary motor cortex: A multi-locus transcranial magnetic stimulation study.

Short-interval intracortical inhibition (SICI) has been studied with paired-pulse transcranial magnetic stimulation (TMS) by administering two pulses at a millisecond-scale interstimulus interval (ISI) to a single cortical target. It has, however, been difficult to study the interaction of nearby cortical targets with paired-pulse TMS. To overcome this limitation, we have developed a multi-locus TMS (mTMS) device, which allows controlling the stimulus location electronically. Here, we applied mTMS to study SICI in primary motor cortex with paired pulses targeted to adjacent locations, aiming to quantify the extent of the cortical region producing SICI in the location of a test stimulus. We varied the location and timing of the conditioning stimulus with respect to a test stimulus targeted to the cortical hotspot of the abductor pollicis brevis (APB) in order to study their effects on motor evoked potentials. We further applied a two-coil protocol with the conditioning stimulus given by an oval coil only to the surroundings of the APB hotspot, to which a subsequent test stimulus was administered with a figure-of-eight coil. The strongest SICI occurred at ISIs below 1 ms and at ISIs around 2.5 ms. These ISIs increased when the conditioning stimulus receded from the APB hotspot. Our two-coil paired-pulse TMS study suggests that SICI at ISIs of 0.5 and 2.5 ms originate from different mechanisms or neuronal elements.

Real-time computation of the TMS-induced electric field in a realistic head model.

Transcranial magnetic stimulation (TMS) is often targeted using a model of TMS-induced electric field (E). In such navigated TMS, the E-field models have been based on spherical approximation of the head. Such models omit the effects of cerebrospinal fluid (CSF) and gyral folding, leading to potentially large errors in the computed E-field. So far, realistic models have been too slow for interactive TMS navigation. We present computational methods that enable real-time solving of the E-field in a realistic five-compartment (5-C) head model that contains isotropic white matter, gray matter, CSF, skull and scalp. Using reciprocity and Geselowitz integral equation, we separate the computations to coil-dependent and -independent parts. For the Geselowitz integrals, we present a fast numerical quadrature. Further, we present a moment-matching approach for optimizing dipole-based coil models. We verified and benchmarked the new methods using simulations with over 100 coil locations. The new quadrature introduced a relative error (RE) of 0.3-0.6%. For a coil model with 42 dipoles, the total RE of the quadrature and coil model was 0.44-0.72%. Taking also other model errors into account, the contribution of the new approximations to the RE was 0.1%. For comparison, the RE due to omitting the separation of white and gray matter was >11%, and the RE due to omitting also the CSF was >23%. After the coil-independent part of the model has been built, E-fields can be computed very quickly: Using a standard PC and basic GPU, our solver computed the full E-field in a 5-C model in 9000 points on the cortex in 27 coil positions per second (cps). When the separation of white and gray matter was omitted, the speed was 43-65 cps. Solving only one component of the E-field tripled the speed. The presented methods enable real-time solving of the TMS-induced E-field in a realistic head model that contains the CSF and gyral folding. The new methodology allows more accurate targeting and precise adjustment of stimulation intensity during experimental or clinical TMS mapping.

The effect of experimental pain on short-interval intracortical inhibition with multi-locus transcranial magnetic stimulation.

Chronic neuropathic pain is known to alter the primary motor cortex (M1) function. Less is known about the normal, physiological effects of experimental neurogenic pain on M1. The objective of this study is to determine how short-interval intracortical inhibition (SICI) is altered in the M1 representation area of a muscle exposed to experimental pain compared to SICI of another muscle not exposed to pain. The cortical representation areas of the right abductor pollicis brevis (APB) and biceps brachii (BB) muscles of 11 subjects were stimulated with a multi-locus transcranial magnetic stimulation device while the resulting motor-evoked potentials (MEPs) were recorded with electromyography. Single- and paired-pulse TMS was administered in seven conditions, including one with the right hand placed in cold water. The stimulation intensity for the conditioning pulses in the paired-pulse examination was 80% of the resting motor threshold (RMT) of the stimulated site and 120% of RMT for both the test and single pulses. The paired-pulse MEP amplitudes were normalized with the mean amplitude of the single-pulse MEPs of the same condition and muscle. SICI was compared between conditions. After the cold pain, the normalized paired-pulse MEP amplitudes decreased in APB, but not in BB, indicating that SICI was potentially increased only in the cortical area of the muscle subjected to pain. These data suggest that SICI is increased in the M1 representation area of a hand muscle shortly after exposure to pain has ended, which implies that short-lasting pain can alter the inhibitory balance in M1.

Multi-locus transcranial magnetic stimulation-theory and implementation.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation. OBJECTIVE: To overcome the limitations of physical TMS-coil movement by introducing electronic targeting. METHODS: We propose electronic stimulation targeting using a set of large overlapping coils and introduce a matrix-factorisation-based method to design such sets of coils. We built one such device and demonstrated the electronic stimulation targeting in vivo. RESULTS: The demonstrated two-coil transducer allows translating the stimulated spot along a 30-mm-long line segment in the cortex; with five coils, a target can be selected from within a region of the cortex and stimulated in any direction. Thus, far fewer coils are required by our approach than by previously suggested ones, none of which have resulted in practical devices. CONCLUSION: Already with two coils, we can adjust the location of the induced electric field maximum along one dimension, which is sufficient to study, for example, the primary motor cortex.

Noninvasive extraction of microsecond-scale dynamics from human motor cortex.

State-of-the-art noninvasive electromagnetic recording techniques allow observing neuronal dynamics down to the millisecond scale. Direct measurement of faster events has been limited to in vitro or invasive recordings. To overcome this limitation, we introduce a new paradigm for transcranial magnetic stimulation. We adjusted the stimulation waveform on the microsecond scale, by varying the duration between the positive and negative phase of the induced electric field, and studied corresponding changes in the elicited motor responses. The magnitude of the electric field needed for given motor-evoked potential amplitude decreased exponentially as a function of this duration with a time constant of 17 µs. Our indirect noninvasive measurement paradigm allows studying neuronal kinetics on the microsecond scale in vivo.

Coil optimisation for transcranial magnetic stimulation in realistic head geometry.

BACKGROUND: Transcranial magnetic stimulation (TMS) allows focal, non-invasive stimulation of the cortex. A TMS pulse is inherently weakly coupled to the cortex; thus, magnetic stimulation requires both high current and high voltage to reach sufficient intensity. These requirements limit, for example, the maximum repetition rate and the maximum number of consecutive pulses with the same coil due to the rise of its temperature. OBJECTIVE: To develop methods to optimise, design, and manufacture energy-efficient TMS coils in realistic head geometry with an arbitrary overall coil shape. METHODS: We derive a semi-analytical integration scheme for computing the magnetic field energy of an arbitrary surface current distribution, compute the electric field induced by this distribution with a boundary element method, and optimise a TMS coil for focal stimulation. Additionally, we introduce a method for manufacturing such a coil by using Litz wire and a coil former machined from polyvinyl chloride. RESULTS: We designed, manufactured, and validated an optimised TMS coil and applied it to brain stimulation. Our simulations indicate that this coil requires less than half the power of a commercial figure-of-eight coil, with a 41% reduction due to the optimised winding geometry and a partial contribution due to our thinner coil former and reduced conductor height. With the optimised coil, the resting motor threshold of abductor pollicis brevis was reached with the capacitor voltage below 600 V and peak current below 3000 A. CONCLUSION: The described method allows designing practical TMS coils that have considerably higher efficiency than conventional figure-of-eight coils.