Biology subjects

Ilmoniemi, R. J.

Publications and source records attributed to Ilmoniemi, R. J..

At least 19 recordsLinked to original sources

bioRxiv2026

Matching Corticospinal and Cortical Excitability along the motor cortex: TMS-EMG-EEG study

There is still no consensus on how to choose intensities for transcranial magnetic stimulation (TMS). The resting motor threshold (RMT), the intensity needed to evoke muscle contractions in the contralateral limb muscles, is a robust muscle-specific index of corticospinal excitability. RMT from one of the hand muscles is commonly used as a reference for TMS neuromodulation interventions and TMS-electroencephalography (EEG) studies. However, it only provides an indirect measure of cortical excitability, and even for the primary motor cortex (M1), we do not understand how cortical and corticospinal excitability correspond to each other. Indeed, it remains unclear whether cortical responses to TMS follow similar location-dependent patterns along the M1, and whether subthreshold stimulation can reliably engage cortical circuits relevant to motor output. Combining TMS with electromyography (EMG) and EEG, TMS-EMG-EEG, enables simultaneous assessment of corticospinal and cortical excitability to answer these questions. We investigated how cortical excitability thresholds (CETs, measured with EEG), relate to corticospinal excitability thresholds (RMTs, measured with EMG) at the hand, arm, and leg hotspots along the M1 in 24 subjects. RMTs and CETs were strongly correlated, and both increased from hand to arm to leg. CETs were generally lower than RMTs, indicating that subthreshold stimulation was enough to evoke robust early TMS evoked potentials (TEPs). Within subjects, CETs differed from the corresponding RMTs at all three M1 hotspots, and this difference increased from hand to leg representations. The findings of the present study argue against using a default hand-muscle RMT to set cortical excitability dosage along the M1 and beyond. Online TMS-EEG can enable real-time dosing and could improve stimulation precision, efficiency, and generalizability, but the site-specific variability calls for adaptive control.

neuroscience↗

bioRxiv2026

Real-time noise cancellation for EEG monitoring and brain-computer interfaces

Raw electroencephalography (EEG) data suffer from a low signal-to-noise ratio (SNR). Effective real-time cleaning of EEG would improve the robustness of EEG monitoring, brain-computer interfaces, and brain-state-dependent stimulation applications in both laboratory and real-life environments. Here, we present a real-time source-estimate-utilizing noise-discarding algorithm (rtSOUND) for EEG noise suppression. We adapted the established offline SOUND algorithm for real-time use and implemented it into an open-source EEG-processing software. Instead of using conventional temporal filtering, SOUND operates the data with a spatial filter. This makes it particularly suitable for real-time applications, since each streamed data sample can be cleaned separately in near real-time. Unlike temporal filtering methods, SOUND does not make assumptions about the frequency content of noise and brain signals but assumes that the noise topographies differ from those generated by brain activity. With an EEG forward model, rtSOUND cross-validates the EEG time series and estimates the spatial distribution of noise, resulting in a data-cleaning linear spatial filter. Each streamed EEG sample is processed synchronously, and the filter is periodically updated in an asynchronous parallel process. The algorithm rapidly updates the spatial filter in response to changes in the data, ensuring that noise reduction is both immediate and accurately adapted to the current EEG state. rtSOUND was validated with transcranial magnetic stimulation (TMS)-EEG and resting-state EEG datasets measured from 25 healthy subjects. SNR of both TMS-evoked potentials and resting-state data consistently improved across various metrics. rtSOUND particularly benefitted channels with poor SNR, while retaining the waveforms in high-quality channels. The algorithm was fast enough to process data streamed at 5 kHz. rtSOUND improves the SNR of EEG in real time, providing a robust method to improve signal quality for brain-state-monitoring applications.

neuroscience↗

bioRxiv2026

Adaptive Bayesian localization of motor representation areas

Transcranial magnetic stimulation (TMS) enables non-invasive localization of cortical motor representations, with important clinical applications in presurgical planning. Existing methods either disregard spatial information about the TMS-induced electric field (E-field) or use acquisition schemes that do not leverage previously elicited motor responses to guide subsequent stimulation. We present an adaptive Bayesian localization method that combines real-time E-field optimization with per-trial probabilistic inference. The cortical origin of the motor responses is represented as a spatial probability distribution that is updated after each stimulus. Subsequent stimuli are then optimized to maximize the expected localization improvement given previous responses. We validated the method experimentally, using multi-locus TMS for adaptive localization and single-coil TMS as a non-adaptive reference with randomized coil placements. Across eight subjects, the adaptive protocol at least halved the number of stimuli required for stable localization compared to the randomized protocol, converging in 60 stimuli on average, with 95% highest-density regions often below 10 mm2 by 150 stimuli.

neuroscience↗

bioRxiv2026

Automated robotic control system for EEG-BCI-guided closed-loop TMS

Brain-state-guided and closed-loop transcranial magnetic stimulation (TMS) protocols have emerged as methods for decreasing the variability and increasing the therapeutic effectiveness of stimulation protocols. However, most existing brain-state-dependent TMS systems only control the timing of stimulation, while the location is fixed and manually adjusted between blocks or sessions. This limits flexible targeting of distributed networks. We developed a system that jointly manages TMS pulse timing and location automatically controlled by an electroencephalography (EEG)-based brain- computer interface (BCI). A machine-learning algorithm infers the brain state in real time to guide the robotic coil placement and target. We present a proof-of-concept study in which a BCI controlled both the target site and the timing of TMS. A pre-trained convolutional neural network discriminated between resting state and movements performed with the right or left hand; the classifier output determined the hemisphere in which primary-motor-cortex hand area was stimulated and when. Preprocessing and decoding of 2-s EEG segments required 150 ms, and the robot took 7.5 s to move from the vertex home position to the predefined motor targets. The EEG-BCI-guided robotic TMS system expands the toolkit for brain-state-dependent and closed-loop neurostimulation by enabling control of stimulus location based on volitional brain activity. Thus, the system can benefit both neuroscience research and clinical neuromodulation applications. A prominent application of the system is automatically controlling spinal cord injury or motor disorder TMS rehabilitation with motor imagery, optimizing stimulation timing to the brain state producing optimal rehabilitation results.

neuroscience↗

bioRxiv2026

TMS timed to interictal epileptiform discharges

Interictal epileptiform discharges (IEDs) are pathological hypersynchronous bursts of electrical brain activity that occur between seizures in patients with epilepsy. IEDs are caused by transient brain states that are difficult to predict, making them a challenging neurophysiological and technological case for brain-state-dependent stimulation. Administering stimulation at IED onset may provide insight into the epileptic network and optimize neurostimulation therapies. Here, we assessed the feasibility of IED-triggered transcranial magnetic stimulation (TMS) in two children with self-limited epilepsy with centrotemporal spikes (SeLECTS), a common pediatric epilepsy in which IEDs emerge from the motor cortex. A convolutional neural network (CNN) was trained on the participants pre-recorded electroencephalography (EEG) data with IEDs annotated by an epileptologist. The CNN was integrated into an EEG-processing pipeline that classified EEG segments as "IED" or "non-IED" in real time. With this pipeline, TMS pulses were administered during IED or non-IED periods in an interleaved, randomized design. We stimulated both the motor cortex generating the IEDs and the contralateral motor cortex and tested the impact of IEDs on TMS-evoked potentials (TEPs). Our study demonstrated that TMS can be timed to IEDs and that there is a site-specific increase in TEP amplitude when stimulating during IEDs. Out of the TMS pulses aimed at an IED, 39% and 19% were successfully delivered during an IED for the two participants, respectively. For future research, we propose ways to address the methodological challenges of IED-timed TMS, enabling brain-state-dependent TMS for epilepsy research and treatment.

neuroscience↗

bioRxiv2026

Distinct cortical excitability and connectivity profiles within the human SMA complex

Introduction and aimUnderstanding brain functions increasingly relies on a network-based perspective, emphasizing interactions across distributed regions. High-order cognitive functions, like language and executive processes, engage such networks rather than isolated cortical areas, yet mapping their dynamics in humans remains challenging. The supplementary motor area (SMA) complex serves as a crucial hub, functioning as an interface between cognitive and sensorimotor processing. Navigated transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) enables causal, time-resolved assessment of cortical excitability and connectivity with high temporal and spatial precision. Extending prior proof-of-concept work, this study aims to provide normative neurophysiological signatures of the SMA complex (pre-SMA and SMA). MethodsTwenty-one healthy subjects underwent a TMS-EEG session where six stimulation targets over the SMA complex (three in pre-SMA, one in the border between pre-SMA and SMA, two in SMA) were recorded. Global cortical excitability via global mean field power (GMFP) was computed over three time-windows (10-50, 50-100, and 100-200 ms) and compared across targets. Normalized power in different frequency bands (, {beta}1, {beta}2, {gamma}) and natural frequency (NF) were also computed and compared across stimulation sites. Then, we calculated tractography-derived connectivity metrics to examine corticothalamic projections from each stimulation site. Apparent fiber density (AFD)-derived connection strength quantified intra-axonal fibre volume along pathways to the whole thalamus, whereas fibre bundle capacity (FBC) assessed the aggregate intra-axonal cross-sectional area at pathway endpoints, providing an estimate of information transmission capacity to each of the 23 thalamic nuclei. ResultsCortical excitability and oscillatory properties varied significantly across TMS targets. A gradient in cortical excitability was observed, where anterior and middle portions of pre-SMA exhibited significantly lower GMFP in the early post-stimulus phase (i.e., 10-50 ms) than SMA portions; interestingly, these differences were clearly dampened in a later time-window (50-100 ms) and disappeared after this period. Furthermore, higher and lower {beta}2 power were observed in anterior pre-SMA than posterior pre-SMA portions. No differences were observed in NF. Crucially, we also observed significant differences in whole- and single-nuclei thalamic structural connectivity. DiscussionThese findings provide direct human in vivo evidence for distinct neurophysiological and structural connectivity profiles of the pre-SMA and SMA, possibly reflecting their different cytoarchitectonic, myeloarchitectonic and connectivity properties. Variations in cortical excitability, oscillatory dynamics, and FBC along the rostro-caudal axis may mirror functional specialization, with pre-SMA supporting cognitive control processes and SMA engaging motor-related thalamocortical networks. Together, the results demonstrate the sensitivity of TMS-EEG and diffusion-weighted connectomics to measure fine-grained neurophysiological differences of corticothalamic projections, which can lead to individualized neuromodulation targeting.

neuroscience↗

bioRxiv2026

TMS-EEG Indices to Define Local Cortical Excitability Thresholds

IntroductionTranscranial magnetic stimulation (TMS) is widely employed to treat various psychiatric and neurological disorders. However, TMS protocols typically rely on generalizations, particularly in selecting stimulation intensities, leading to suboptimal and variable outcomes. Combining TMS with electroencephalography (EEG) offers a potential solution by allowing direct monitoring of stimulation effects. In this study, we investigate how features of the TMS-EEG signal change with intensity to identify thresholds implying qualitative shifts in the brain response. MethodsWe stimulated eight subjects at both the primary motor cortex (M1) and the pre-supplementary motor area (pre-SMA) with navigated TMS at 15 closely spaced intensities and measured TMS-evoked EEG responses (TMS-evoked potential, TEP) with 60 trials per intensity. TEP thresholds were identified with three methods: by selecting the intensity where the TEP peak-to-peak exceeds 6 V, or by fitting either piecewise-linear or sigmoid curves into the power spectral density (PSD) frequency components to identify nonlinear intensity behavior. ResultsThe identified TEP thresholds varied depending on subject, target, and identification method. In M1, the thresholds attained with the fixed-amplitude and piecewise PSD fit methods averaged around the motor threshold, and in pre-SMA around 120% of the motor threshold. The TEP thresholds yielded by the sigmoid fit method were higher in intensity, and least consistent between subjects. ConclusionsOur findings support the hypothesis that detectable changes in EEG patterns occur at specific TMS intensities. These results provide a basis for individualized stimulation dosing, potentially enhancing therapeutic efficacy and reliability. Future research should focus on refining these methods and validating their clinical applicability across diverse conditions and patient populations.

neuroscience↗

bioRxiv2025

Fast and standardized motor-hotspot determination with automated TMS mapping

Determining the optimal stimulation target for motor responses (motor hotspot) and the required intensity for reliably eliciting said responses (motor threshold) are common procedures in transcranial magnetic stimulation (TMS) research and treatments. However, the procedures for determining them are user-dependent, slow, and lack standardization, leading to long stimulation sessions with potentially inadequate outcomes. Partially automated algorithms for determining the motor threshold have been developed, but the motor hotspot is still largely mapped by hand. Automating the hotspot mapping will accelerate the process and improve standardization and accuracy. We developed a fully automated algorithm for finding the motor hotspot with multi-locus TMS and Bayesian optimization. Tested online in five healthy participants, the algorithm located motor hotspots with (mean {+/-} 95% CI) 2.1 {+/-} 0.7 mm and 6 {+/-} 2{degrees} difference from the global best target with only (mean) 47 stimuli. This is a significant improvement from previous motor-mapping algorithms, which do not optimize for stimulation location and orientation simultaneously. This accurate, fast, and user-independent procedure paves the way for faster experimental processes and more streamlined clinical applications.

neuroscience↗

bioRxiv2025

A High-Precision Timing Method and Digital Interface for Closed-Loop TMS

ObjectiveCurrent transcranial magnetic stimulation (TMS) protocols exhibit high inter-subject variability in treatment outcomes, highlighting the need for personalized, brain-state-dependent closed-loop stimulation protocols. To enable such protocols, we aim to provide robust, precisely timed external control of TMS, with stimulation timed relative to feedback signals such as the electroencephalogram (EEG). ApproachCommercial TMS devices typically rely on trigger signals for precise external pulse timing, while adjusting stimulation parameters, such as intensity, is better handled via serial digital communication, which supports robust error detection and feedback. However, combining these communication methods is inherently complex and prone to timing issues, such as race conditions. Furthermore, trigger signals lack capabilities essential for real-time systems, such as preventing late pulse delivery. We present a method for precise and accurate pulse timing, implemented through a digital interface that uses exclusively serial digital messaging, eliminating the need for trigger signals. This interface enables external control of pulse timing, intensity, and other parameters. The TMS device maintains its own internal clock and delivers pulses at pre-scheduled times, decoupling timing precision from the control device. Additionally, we propose a method for synchronizing such time-tracking TMS devices with commercial EEG systems, enabling precisely timed EEG-TMS. Main resultsUsing these methods, our custom TMS device delivered pulses precisely aligned to the EEG signal, with timing errors consistently below 0.3 ms. These errors were constrained by the experimental setup, including the sampling rate of our EEG device and the signal-to-noise ratio affecting pulse detection. SignificanceOur timing method achieves sub-millisecond precision in brain-state-dependent closed-loop EEG-TMS, providing a foundation for robust TMS timing that supports adaptive, personalized stimulation protocols. The digital control interface, co-designed with our TMS device, integrates pulse timing and parameters, setting a precedent for future advancements in computer-controlled TMS.

bioengineering↗

bioRxiv2025

NeuroSimo: an open-source software for closed-loop EEG- or EMG-guided TMS

ObjectiveOur goal was to create open-source software for closed-loop EEG-TMS that allows researchers to rapidly prototype and develop novel stimulation paradigms in a high-level programming language. This addresses the limitations of current solutions, which often rely on proprietary hardware and software, limiting their accessibility and customizability, or comprise ad-hoc pipelines tailored to specific use cases. ApproachWe developed NeuroSimo, a software platform that enables arbitrary EEG-TMS stimulation protocols written in Python, leveraging Pythons ecosystem of scientific, neuroimaging, and machine learning libraries. The core software is written in C++ with an embedded Python interpreter and employs the Robot Operating System (ROS 2) for inter-process communication. NeuroSimo runs on real-time-enabled Linux Ubuntu, using LabJack T4 for pulse triggering, and supports two EEG device models (Bittium NeurOne, BrainProducts actiCHamp) and TMS devices that deliver pulses via trigger signals. The software includes a graphical user interface for configuration and performance monitoring, and supports GPU processing for neural network computations. Main resultsIn brain-state-dependent stimulation using the Phastimate algorithm, which targets TMS pulses to the trough of sensorimotor -rhythm, NeuroSimo achieved a median timing error of 0.2 ms (95% CI: 0.2-0.2 ms), a 99th-percentile of 0.6 ms (0.6-0.6 ms), and a maximum of 1.4 ms. SignificanceAs an open-source platform combining Pythons flexibility with real-time closed-loop EEG-TMS, NeuroSimo enables researchers to develop and implement novel therapeutic approaches, marking a significant advance in personalized brain stimulation.

bioengineering↗

bioRxiv2025

The dependency of TMS-evoked potentials on electric-field orientation in the cortex

Transcranial magnetic stimulation (TMS) stimulates the brain by electromagnetic induction. The outcome depends on multiple stimulation parameters such as the induced electric-field pattern (in particular, the location of the peak field and its orientation), intensity and timing. However, it is not clear how the TMS-evoked responses are affected by all the stimulation parameters. This study elucidates the dependency of the TMS-evoked electroencephalography (EEG) responses on the orientation of the stimulating electric field. To achieve this, we analysed a dataset from six subjects who were given pulses with 36 stimulus orientations to the pre-supplementary motor area (pre-SMA). The TMS-evoked potentials (TEPs) and induced oscillations were analysed with cluster-based statistics. Source estimation was performed to assess the effects of stimulus orientation on the TMS-evoked signal propagation. The amplitudes of the early peaks (20 and 40 ms after the TMS pulse) strongly depended on the electric field orientation. Our analysis suggested orientation dependency up to 100 ms post-stimulus in most subjects, indicating changes in stimulation efficacy and potential changes in signal propagation from the stimulated site. These results suggest that different orientations may perturb different networks. Thus, the orientation is a crucial parameter for the stimulation outcome and should be adjusted according to the cortical network under investigation.

neuroscience↗

bioRxiv2023

A multi-channel TMS system enabling accurate stimulus orientation control during concurrent ultra-high-field MRI for preclinical applications

Monitoring cortical responses to neuromodulation protocols on preclinical models can elucidate fundamental mechanisms of brain function. Concurrent brain stimulation and imaging is challenging, usually compromising spatiotemporal resolution, accuracy, and versatility. Here we report a non-invasive brain stimulation system with electronic control of neuromodulation parameters in a 9.4-T magnetic resonance imaging (MRI) environment. In the imaging scanner, transcranial magnetic stimulation is delivered with a set of two coils and the MRI signals are recorded with a radiofrequency coil. The coil set provides millisecond-scale electronic control of the stimulus orientation with 1{degrees} resolution. Without physically rotating the coils, we evoked orientation-specific muscle responses after cortical stimulation on an anesthetized rat. We show that the stimulation pulses do not affect the anatomical imaging quality, and imaging signals are disrupted only if recorded before 10 ms after pulse delivery. Concurrent electronically targeted brain stimulation and neuroimaging sets the stage for the causal investigation of whole-brain network functions, endorsing more efficient treatment protocols.

neuroscience↗

bioRxiv2023

Intrinsic motor network connectivity predicts corticospinal excitability

State-dependent non-invasive brain stimulation (NIBS) informed by electroencephalography (EEG) has contributed to the understanding of NIBS inter-subject and inter-session variability. While these approaches focused on local EEG characteristics, it is acknowledged that the brain exhibits an intrinsic long-range dynamic organization in networks. This proof-of-concept study explores whether EEG connectivity of the primary motor cortex (M1) in the pre-stimulation period aligns with the motor network (MN) and how MN state affects responses to transcranial magnetic stimulation (TMS) of M1. One thousand suprathreshold TMS pulses were delivered to left M1 in 8 subjects at rest, with simultaneous EEG. Motor evoked potentials (MEPs) were measured from the right hand. Source-space functional connectivity of left M1 to the whole-brain was assessed using the imaginary part of the Phase Locking Value at the frequency of the sensorimotor {micro}-rhythm in a 1-second window before the pulse. Group-level connectivity revealed functional links between left M1, left supplementary motor area, and right M1. Also, pulses delivered at high MN connectivity states result in a greater MEP amplitude compared to low connectivity states. At single-subject level, this relation is more expressed in subjects that feature an overall high cortico-spinal excitability. In conclusion, this study paves the way for MN connectivity based NIBS. HighlightsO_LIEEG pre-stimulus connectivity of left M1 largely corresponds to the motor network C_LIO_LIStronger motor network (MN) connectivity corresponds to greater MEP amplitudes C_LIO_LILinear regression models based on MN connectivity predicts MEP amplitude C_LI

neuroscience↗

bioRxiv2023

Real-time tractography-assisted neuronavigation for TMS

BackgroundState-of-the-art navigated transcranial magnetic stimulation (nTMS) systems can display the TMS coil position relative to the structural magnetic resonance image (MRI) of the subjects brain and calculate the induced electric field. However, the local effect of TMS propagates via the white-matter network to different areas of the brain, and currently there is no commercial or research neuronavigation system that can highlight in real time the brains structural connections during TMS. ObjectiveTo develop a real-time tractography-assisted TMS neuronavigation system and investigate its feasibility. MethodWe propose a modular framework that seamlessly integrates offline (preparatory) analysis of diffusion MRI data with online (real-time) tractography. For tractography and neuronavigation we combine our custom software Trekker and InVesalius, respectively. We evaluate the feasibility of our system by comparing online and offline tractography results in terms of streamline count and their overlap. ResultsA real-time tractography-assisted TMS neuronavigation system is developed. Key features include the application of state-of-the-art tractography practices, the ability to tune tractography parameters on the fly, and the display of thousands of new streamlines every few seconds using a novel uncertainty visualization technique. We demonstrate in a video the feasibility and quantitatively show the agreement with offline filtered streamlines. ConclusionReal-time tractography-assisted TMS neuronavigation is feasible. With our system, it is possible to target specific brain regions based on their structural connectivity, and to aim for the fiber tracts that make up the brains networks.

neuroscience↗

bioRxiv2021

Local brain-state dependency of effective connectivity: evidence from TMS-EEG

BackgroundSpontaneous cortical oscillations have been shown to modulate cortical responses to transcranial magnetic stimulation (TMS). If not controlled for, they might increase variability in responses and mask meaningful changes in the signals of interest when studying the brain with TMS combined with electroencephalography (TMS-EEG). To address this challenge in future closed-loop stimulation paradigms, we need to understand how spontaneous oscillations affect TMS-evoked responses. ObjectiveTo describe the effect of the pre-stimulus phase of cortical mu (8-13 Hz) and beta (13-30 Hz) oscillations on TMS-induced effective connectivity patterns. MethodsWe applied TMS to the left primary motor cortex and right pre-supplementary motor area of three subjects while recording EEG. We classified trials off-line into positive- and negative-phase classes according to the mu and beta rhythms. We calculated differences in the global mean-field amplitude (GMFA) and compared the cortical spreading of the TMS-evoked activity between the two classes. ResultsPhase had significant effects on the GMFA in 11 out of 12 datasets (3 subjects x 2 stimulation sites x 2 frequency bands). Seven of the datasets showed significant differences in the time range 15-50 ms, nine in 50-150 ms, and eight after 150 ms post-stimulus. Source estimates showed complex spatial differences between the classes in the cortical spreading of the TMS-evoked activity. ConclusionsTMS-evoked effective connectivity appears to depend on the phase of local cortical oscillations at the stimulated site. This may be crucial for efficient design of future brain-state-dependent and closed-loop stimulation paradigms.

neuroscience↗

bioRxiv2021

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

BackgroundTranscranial 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. ObjectiveTo develop an mTMS system that allows adjusting the location and orientation of the E-field maximum within a cortical region. MethodsWe 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. ResultsThe 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. ConclusionThe developed mTMS system enables electronically targeted brain stimulation within a cortical region.

neuroscience↗

bioRxiv2021

The rt-TEP tool: real-time visualization of TMS-evoked potentials to maximize cortical activation and minimize artifacts

BackgroundThe impact of transcranial magnetic stimulation (TMS) on cortical neurons is currently hard to predict based on a priori biophysical and anatomical knowledge alone. This problem can hamper the reliability and reproducibility of protocols aimed at measuring electroencephalographic (EEG) responses to TMS. New MethodWe introduce and release a novel software tool to facilitate and standardize the acquisition of TMS-evoked potentials (TEPs). The tool, rt-TEP (real-time TEP), interfaces with different EEG amplifiers and offers a series of informative visualization modes to assess in real time the immediate impact of TMS on the underlying neuronal circuits. ResultsWe show that rt-TEP can be used to abolish or minimize magnetic and muscle artifacts contaminating the post-stimulus period thus affording a clear visualization and quantification of the amplitude of the early (<50 ms) EEG response after averaging a limited number of trials. This real-time readout can then be used to adjust TMS parameters (e.g. site, orientation, intensity) and experimental settings (e.g. loudness and/or spectral features of the noise masking) to ultimately maximize direct cortical effects over the undesired sensory effects of the coils discharge. Comparison with Existing MethodsThe ensemble of real-time visualization modes of rt-TEP are not implemented in any current commercial software and provide a key readout to titrate TMS parameters beyond the a priori information provided by anatomical models. ConclusionsReal-time optimization of stimulation parameters with rt-TEP can facilitate the acquisition of reliable TEPs with a high signal-to-noise ratio and improve the standardization and reproducibility of data collection across laboratories. HighlightsO_LIrt-TEP provides an immediate EEG readout to assess the quality of TEPs in real time C_LIO_LIrt-TEP interfaces with most commercial EEG systems C_LIO_LIInformative, real time visualization allows maximising the cortical impact of TMS while minimizing artifacts C_LIO_LIrt-TEP facilitates the acquisition of reliable TEPs with a high signal-to-noise ratio C_LI

neuroscience↗

bioRxiv2021

Closed-loop optimization of transcranial magnetic stimulation with electroencephalography feedback

BackgroundTranscranial magnetic stimulation (TMS) is widely used in brain research and treatment of various brain dysfunctions. However, the optimal way to target stimulation and administer TMS therapies, for example, where and in which electric field direction the stimuli should be given, is yet to be determined. ObjectiveTo develop an automated closed-loop system for adjusting TMS parameters (in this work, the stimulus orientation) online based on TMS-evoked brain activity measured with electroencephalography (EEG). MethodsWe developed an automated closed-loop TMS-EEG set-up. In this set-up, the stimulus parameters are electronically adjusted with multi-locus TMS. As a proof of concept, we developed an algorithm that automatically optimizes the stimulation orientation based on single-trial EEG responses. We applied the algorithm to determine the electric field orientation that maximizes the amplitude of the TMS- EEG responses. The validation of the algorithm was performed with six healthy volunteers, repeating the search twenty times for each subject. ResultsThe validation demonstrated that the closed-loop control worked as desired despite the large variation in the single-trial EEG responses. We were often able to get close to the orientation that maximizes the EEG amplitude with only a few tens of pulses. ConclusionOptimizing stimulation with EEG feedback in a closed-loop manner is feasible and enables effective coupling to brain activity.

bioengineering↗