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TMS-related potentials and artifacts in combined TMS-EEG measurements: Comparison of three different TMS devices Gestion des artefacts lors de la mesure des potentiels liés à la stimulation magnétique transcrânienne (SMT) lors des enregistrements combinés EEG-SMT : comparaison de trois systèmes J. Van Doren , B. Langguth , M. Schecklmann ∗ University of Regensburg, Department of Psychiatry and Psychotherapy, Universitaetsstrasse 84, 93053 Regensburg, Germany Received 11 September 2014; accepted 15 February 2015
KEYWORDS Transcranial magnetic stimulation; Electroencephalography; Artifact; Evoked potential; Magnetic field
∗
Summary Objectives. — Simultaneous use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows the measurement of TMS-induced cortical activity. A challenge in the interpretation of the cortical responses to TMS pulses is the differentiation between stimulation artifacts and cortical signals. Thus, we investigated TMS-evoked potentials and artifacts with respect to different TMS devices. Methods. — Physical properties of the magnetic field produced by a MagStim® , Magventure® and Deymed® stimulator were determined. Six subjects were stimulated over the left motor cortex hot spot of the right index finger 42 times with 120% motor threshold, while wearing a 60-electrode EEG cap. Results. — For each device we found a linear increase of field strength with a linear increase of machine output. The Magventure® system differed from the MagStim® and the Deymed® system with respect to field strength (higher), magnetic flux duration (shorter), motor threshold (lower), recovery time from the TMS artifact (shorter), motor evoked potentials (MEPs) latency (shorter), and had a reversed first artifact trajectory. There were no differences with respect to validity of the MEPs (number of valid epochs), MEP amplitudes, latency or amplitude of the second TMS artifact, or latency or amplitude of TMS-evoked potentials (TEPs).
Corresponding author. Tel.: +49 941 941 2054; fax: +49 941 941 2065. E-mail address: [email protected] (M. Schecklmann).
http://dx.doi.org/10.1016/j.neucli.2015.02.002 0987-7053/© 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Van Doren J, et al. TMS-related potentials and artifacts in combined TMS-EEG measurements: Comparison of three different TMS devices. Neurophysiologie Clinique/Clinical Neurophysiology (2015), http://dx.doi.org/10.1016/j.neucli.2015.02.002
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J. Van Doren et al. Conclusions. — All of the used devices are well suited for TMS-EEG measurements, but the technical differences (e.g., pulse length) should be taken into account for the interpretation of the results of these experiments. Our results further confirm that adjustment of the stimulation intensity according to individual motor threshold seems to be an effective method to obtain comparable MEP and TEP amplitudes with different stimulation devices. © 2015 Elsevier Masson SAS. All rights reserved.
MOTS CLÉS Stimulation magnétique transcrânienne ; Électroencéphalographie ; Artefact ; Potentiels évoqués ; Champ magnétique
Résumé But de l’étude. — L’enregistrement de l’EEG au cours de la stimulation magnétique transcrânienne (SMT) permet la mesure de potentiels liés à la SMT. L’interprétation de ceux-ci se heurte à la difficulté de différencier les artefacts de stimulation et les réponses d’origine cérébrale. Trois systèmes d’enregistrement ont été comparés par rapport à ce problème. Méthodes. — Nous avons déterminé les propriétés physiques des champs magnétiques produits par les stimulateurs MagStim® , Magventure® et Deymed® . Six sujets porteurs d’un casque EEG à 60 électrodes ont été stimulés à 42 reprises en regard de l’aire de représentation de l’index droit, à 120 % du seuil moteur. Résultats. — Pour chaque système, l’intensité du champ a augmenté linéairement en fonction de la sortie annoncée du stimulateur. Le système Magventure® se différenciait des deux autres sur base de l’intensité du champ (plus élevée), de la durée du flux magnétique (plus courte), du seuil moteur (plus faible), du temps de récupération de l’artefact (plus court), du temps de latence du potentiel moteur (plus court) ; il montrait de surcroît une inversion de la première partie de l’artefact. Par contre, aucune différence ne fut constatée au niveau du nombre d’époques acceptables, des amplitudes des potentiels moteurs, du temps de latence ou de l’amplitude du second artefact ou du temps de latence ou de l’amplitude des potentiels liés à la SMT. Conclusions. — Alors que tous les systèmes étudiés sont bien adaptés aux enregistrements simultanés EEG-SMT, des différences techniques doivent être prises en compte en vue de l’interprétation des résultats. Nos résultats confirment que l’ajustement de la puissance de stimulation sur base des seuils moteurs individuels constitue la meilleure garantie d’obtention de potentiels moteurs ou liés à la SMT comparables lorsqu’ils ont été obtenus au moyen de systèmes de stimulation différents. © 2015 Elsevier Masson SAS. Tous droits réservés.
Introduction Transcranial magnetic stimulation (TMS) is a tool for noninvasive stimulation of the brain that is widely being used to study healthy and diseased cortical function [22]. It is additionally being developed as a therapeutic intervention in neuro-psychiatric disorders such as schizophrenia [1], depression [8], and tinnitus [13] and is being explored as possible technique for the enhancement of cognitive functions [15]. In summary, effect sizes for these approaches are small to moderate. To enhance the efficacy of TMS, it is necessary to increase the knowledge about the exact neurophysiological mechanism of TMS over the various brain regions. For this, combined measurements of TMS and electroencephalography (EEG) are highly recommended since EEG can measure fast TMS-induced neural activity with high temporal resolution. The challenge is to differentiate the neural response to TMS from the relatively large artifacts created by the TMS pulse. Many techniques have been suggested for the minimization of this artifact, such as good electrode impedance (< 5k), not stimulating over highly muscular areas (stick to the midline), avoiding auditory and startle reflex artifacts by using earplugs and/or masking, and avoiding somatosensory artifacts by dampening the coil vibration on the head by using foam [9,16,23,28]. In addition, hardware modification
and a variety of offline data analyses have been suggested to improve the quality of data [7,26,29,10]. The TMS artifact is characterized as a sharp first peak starting at the time of stimulation and lasting 5 ms [28] followed by a second artifact occurring around 5—10 ms post-stimulation [19]. The first artifact is attributable to the electrical charge generated by the TMS pulse, while the second is thought to be of muscular origin [19]. This first artifact is to distinguish from a later artifact in some types of machines generated by the recharging of the TMS device. The signals of interest for stimulation of the motor cortex are motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs). Both are well characterized and are considered valid measurements of the effect of the TMS pulse on the brain. The MEP is a biphasic, evoked activity with a specific latency that is detected by electromyography in the corresponding muscle of the stimulated homunculus area. It is the result of the net activation of the motor cortex, propagated via activation of pyramidal cells and the cortico-spinal tract, with a specific conductance time to the muscle in the periphery. The TEPs are EEG-evoked potentials with various peaks including the P60 and the N100 [19,2,14]. The P60 is thought to be a signal that is evoked from the sulci of the primary motor cortex and reflective of inhibition [12], whereas the N100 has been described as a neural correlate of inhibition and associated to attention [3,17]. Both peaks additionally
Please cite this article in press as: Van Doren J, et al. TMS-related potentials and artifacts in combined TMS-EEG measurements: Comparison of three different TMS devices. Neurophysiologie Clinique/Clinical Neurophysiology (2015), http://dx.doi.org/10.1016/j.neucli.2015.02.002
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TMS-EEG artifacts have been suggested to reflect a resetting effect of the TMS pulse on the oscillatory activity of the brain [18]. Only recently TMS-induced artifacts and -evoked potentials produced by different TMS machines have been compared and have been found to be highly reproducible [19]. However, it is known that differences in technical parameters (e.g., pulse duration and form) can influence the induced activity in the brain [21,24] and TMS machines from different manufacturers may vary in the time course, the spatial distribution and the maximum strength of the induced magnetic field. Thus, the purpose of this study is to compare and characterize the signal (MEPs and TEPs) and artifacts (first and second artifacts) in combined TMS-EEG measurements using two common (Magventure® Magpro, Magventure® , Denmark; MagStim® Rapid, MagStim® Co. LTD, United Kingdom) and one novel TMS machine (Deymed® DuoMag XT-100, Deymed® Diagnostic, Czech Republic). First, we characterized maximal strength and duration of the induced magnetic field at different stimulation intensities. Second, we measured the TMS associated first and second artifacts, motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) in six healthy subjects.
Methods Sample and procedures Six healthy students (4 female; 24.6 ± 2.3 years) from the University of Regensburg participated in this study after providing written informed consent. The study was approved by the local ethics committee of the University of Regensburg. All participants had no previous or present severe somatic, neurological, or psychiatric problems. Participants were comfortably seated in a clinical armchair for the duration of the experiment. First, the resting motor threshold was obtained for each machine with the electrode cap on the head. Second, the impedances were lowered to below 5 k. Third, the stimulation took place with a balanced order of the machines, which was randomized to the single participants. For the TMS-EEG measurement, subjects were instructed to sit as still as possible with eyes closed and TMS clicks were masked with white noise applied via insert earplugs. Field strength and duration measurements of the TMS pulses were performed in separate sessions.
Magnetic field To determine if there were possible differences between machine outputs, we tested the magnetic field strength of each machine using a 475 DSP Gaussmeter with a HMMT6J18-VR probe (Lakeshore Inc., USA). The probe was taped to and aligned with the center of the coil. Measurements were made in triplicate for each machine at 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, and 100% of the machine intensity. Additionally, the duration of the magnetic field was measured by the voltage change induced in a wire loop with a diameter of 2 cm placed in the center of the coil. All stimulation devices produced biphasic stimuli. The biphasic magnetic field has the form of a sine wave and the voltage change is calculated by the temporal derivation of
3 the magnetic field (U = −˚/t; U = voltage; ˚ = magnetic flux; t = time; = difference). The voltage change is indicated by a cosine wave, which was present for all three stimulators. Duration of the magnetic field was indicated by return of the voltage change to baseline. For measurement of the voltage change we used a Tektronix TDS 1002 oscilloscope (Tektronix Inc., USA).
Transcranial magnetic stimulation TMS was applied with three different TMS machines and figure of eight coils (see Table 1). The coil was held at a 45-degree angle to the mid-sagittal line with the handle pointing backwards. The motor hotspot was determined by placing the center of the coil over C3 as the starting point and adjusting the coil until the highest motor-evoked potential was reliably obtained from the right first dorsal interosseous muscle. For five subjects the hotspot was in close proximity to C3; for one participant it was localized near C1. Hotspot and orientation of the coils were comparable over the three devices. The resting motor threshold defined as the lowest threshold at which a motor potential was obtained with an amplitude of at least 50 V in four out of eight stimulations [20] was determined for each machine individually and the stimulation intensity was 120% of each individual threshold. For each machine, 42 pulses spaced about 5 seconds apart were triggered manually.
Electrophysiological measurements For EEG and EMG, we used a BrainAmp amplifier (Brain Products GmbH, Germany) with TMS compatible Ag/AgCl sintered pin electrodes (EASYCAP GmbH, Germany). For the EEG measurement, 60 head electrodes with the reference over FCz and the ground over AFz were used according to the international 10-10 EEG system. For determination of the motor-evoked potentials two Ag/AgCl sintered ring electrodes were placed on the right first dorsal interosseous muscle in a tendon belly montage. Signals were recorded with BrainVision Recorder 1.2 with a sampling rate of 5000 Hz using a DC low cut-off and a high cut-off filter of 1000 Hz.
Data and statistical analysis EEG analysis was performed using Brain Vision Analyzer 1.0 (Brain Products, Germany) and the EEGLAB toolbox [4] made for Matlab 2012 (MathWorks Inc., USA). Triggers were placed manually using Brain Vision Analyzer at the first point of deviation from baseline activity near the TMS-induced artifact. These markers were used for further analysis as artifact onset. The EMG data was analyzed using a bipolar montage. The EEG data was first re-referenced to an average reference and then segmented from one second before to one second after the trigger point. Baseline correction was applied from —500 ms to —110 ms according to Rogasch et al. [19]. No filtering of the signal was used. Trials that did not produce a clear MEP (biphasic trajectory) were excluded from further analysis. Analysis was performed using the motor hotspot electrode for each participant (C3 for 5 participants and C1 for one participant). The second artifact, TEPs and MEPs were analyzed both for minimum and maximum peaks as elicited by peak detection algorithms in Vision
Please cite this article in press as: Van Doren J, et al. TMS-related potentials and artifacts in combined TMS-EEG measurements: Comparison of three different TMS devices. Neurophysiologie Clinique/Clinical Neurophysiology (2015), http://dx.doi.org/10.1016/j.neucli.2015.02.002
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J. Van Doren et al. Table 1
Technical information regarding the used TMS systems.
TMS machine
Company, location
Pulse length (s)a
Diameter of coil (mm)
Coil name
Pulse typea
Magventure® Magpro MagStim® Rapid Deymed® DuoMag XT-100
Magventure® , Denmark MagStim® Co. LTD, United Kingdom Deymed® Diagnostic, Czech Republic
320
65
MCF-B65
Biphasic
380
70
D70-alpha
Biphasic
380
70
70-BF
Biphasic
a
As elicited by own measurements.
Analyzer. All segments were visually inspected for the accuracy of the peak detection and adjusted accordingly. In the EEG, one positive and one negative peak were found from 4—12 ms for the second artifact and from 30 to 160 ms for the TEPs (P60 and N100). In the electromyogram the period from 20 to 50 ms was inspected for the MEPs. Latency was defined as the latency of the first maximum/minimum. This method was chosen in analogy to the peak detection of the TEPs. Amplitude was analyzed with respect to the peak-to-peak amplitude difference between the positive and negative peak. Dependent variables (TMS artifacts, TEPs, MEPs) were evaluated for both individual participant trials and averaged for individual participants. The individual averages were then used for statistical analysis. Recovery time from the TMS pulse was assessed according to Rogasch et al. [19]. First, we calculated the standard deviation of the baseline multiplied by three, which is considered to be representative of common resting state EEG activity. Second, data bins were categorized to fall outside or inside of this value starting at the trigger. The time in which the data moved from outside to inside of this common resting state activity is defined as the recovery time from the TMS artifact. In addition to the mean values, we calculated the coefficient of variation (CV) as an indicator for variability. CV is defined by the standardization of the standard deviation (SD) to the individual mean value ((SD/mean) × 100). CV was calculated for amplitude measures of the MEPs, the second TMS artifacts, and the TEPs. The first artifact was not statistically assessed due to saturation effects in the majority of segments. Statistical analysis was performed using SPSS 21.0 (IBM, Armonk, New York, USA). Due to small sample size, we used non-parametric statistics such as the Friedman test (comparison of all machines) and the Wilcoxon signed-rank test (post-hoc test in the case of a significant Friedman test) to compare differences between the machines. Significance threshold was set to 5%. Raw data are depicted as mean ± standard deviation if not otherwise stated.
Results Side effects The only reported side effect for all machines was sensation on the scalp and muscle below the coils. During stimulation
Figure 1 Magnetic field strength values (max: maximum positive value; min: minimum negative value; please note that the pulse is biphasic, producing positive and negative values).
with the Deymed® system, five out of six subjects reported tingling in the nose. For the other devices no such sensation was reported.
Magnetic field strength Magnetic field strength was found to increase linearly for all three machines with differences in the strength of the magnetic field (see Fig. 1). The Magventure® device induced the strongest field with small differences in the positive values between the MagStim® and the Deymed® system. Duration of the magnetic field as elicited by voltage changes was about 320 s for Magventure® and 380 s for the MagStim® and Deymed® machines.
Motor threshold (MT) The motor threshold (Deymed® : 55.7% ± 6.1 (2.7 T); MagStim® : 55.3% ± 6.1 (2.8 T); Magventure® : 48.0% ± 5.6 (2.78 T)) was significantly different between the machines (P = 0.006). The Magventure® differed from the MagStim® (P = 0.027) and the Deymed® system (P = 0.027); the
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TMS-EEG artifacts
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MagStim® and the Deymed® system (P = 0.577) did not differ. We derived the magnetic field strength values corresponding to the mean motor threshold for each machine from Fig. 1 (values in brackets above) indicating that the magnetic field strength is comparable over the machines despite differences in MT.
Motor-evoked potentials (MEP) Before analysis, segments were visually inspected for valid MEP trajectories. The number of kept segments (Deymed® = 82.3%; MagStim® = 81.7%; Magventure® : 75.0%) was not statistically different between the machines (P = 0.846). MEPs did vary in latency, as indicated by the first peak of the MEP, between Magventure® and the other machines (P = 0.011; Deymed® = 27.7 ± 2.5 ms; MagStim® = 27.6 ± 2.7 ms; Magventure® = 26.8 ± 2.3 ms) in which the Magventure® machine elicited MEPs slightly faster than the Deymed® (P = .028) and MagStim® (P = .028) machines, while Deymed® and MagStim® did not differ from each other (P = 0.600). However there was no difference in amplitude on average (P = 0.607) or variability level of the peak-to-peak amplitude (P = 0.607; CV: Deymed® : 56.2% ± 23.1; MagStim® : 61.6% ± 14.4; Magventure® : 54.8% ± 13.7).
Figure 2 Second artifact grand average values (max: maximum positive value; min: minimum negative value).
TMS artifacts The first artifact for the MagStim® and the Deymed® system was characterized in the grand averaged data by a sharp negative peak after TMS stimulation followed by a large positive peak within 2 ms after the TMS pulse onset. The peaks created by the Magventure® system were similar in latency, but began instead with a sharp positive peak followed by a negative peak. The second artifact for all three machines was characterized by a positive peak around 5 ms after TMS stimulation and a negative peak around 8 ms. There was no difference between machines in relation to latency (P = 0.350) or peak-to-peak amplitude difference score (P = 0.513). CV for the amplitude difference was not significant between the machines (P = 0.607; Deymed® : 16.4% ± 7.1; MagStim® : 22.4% ± 9.3; Magventure® : 27.7% ± 15.3). For details see Table 2 and Fig. 2. Recovery time varied significantly between the machines (P = 0.009; Deymed® : 6.9 ms ± 1.1; MagStim® : 7.0 ms ± 1.0; Magventure® : 6.0 ms ± 0.9). The recovery time of the Magventure® device was significantly shorter than for the Deymed® (P = 0.028) and the MagStim® (P = 0.028) systems. CV of recovery time was not significantly different (P > 0.999; Deymed® : 3.07% ± 1.7; MagStim® : 4.02% ± 3.2; Magventure® : 8.02% ± 7.0). Baseline activity was additionally significantly different for the Magventure® system (P = 0.011; Deymed® : 4.35 V ± 1.6; MagStim® : 4.2 V ± 1.6; Magventure® : 9.1 V ± 1.7) compared to the Deymed® (P = 0.028) and MagStim® (P = 0.028) systems, while Deymed® and MagStim® did not differ from one another (P = 0.753).
Figure 3 TEP grand average (P60 and N100 indicated TMSevoked potentials).
TMS-evoked potentials All machines elicited a similar pattern of peaks; a P60 and N100 were apparent (see Fig. 3). The latency (P = 0.223) and amplitude difference score (P = 0.223) did not differ between machines. However, the CV of the amplitude difference score differed between the machines (P = 0.042). The Magventure® CV was significantly different than that of the MagStim® machine (P = 0.028), but not the Deymed® (P = 0.345). The Deymed® and MagStim® machines did not differ (P = 0.463). The CV values for each machine: Deymed® = 17.0% ± 4.4, MagStim® = 22.2% ± 7.9, Magventure® = 15.4% ± 7.4. The Magventure® system was noisier than the other two, as seen by line noise. This artifact was seen in all channels, not only those under the coil.
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J. Van Doren et al. Table 2 Mean latency of the first peak, amplitude difference of the first and second peak and coefficient of variation (CV) of the amplitude difference for motor-evoked potentials (MEP), second artifact, and TMS-evoked potentials (TEP).
MEP Deymed® MagStim® Magventure® Second artifact Deymed® MagStim® Magventure® TEP Deymed® MagStim® Magventure® * **
Latency first peak (ms)
Amplitude difference (V)
CV of amplitude difference (%)
27.7 ± 2.5 27.6 ± 2.7 26.8 ± 2.3*
1346.5 ± 1377.8 1190.0 ± 1247.4 1228.9 ± 945.7
56.2 ± 23.1 61.6 ± 14.4 54.8 ± 13.7
5.3 ± 0.7 5.3 ± 0.3 5.1 ± .2
333.8 ± 248.0 234.12 ± 188.2 396.0 ± 237.00
16.4 ± 7.1 22.4 ± 9.3 27.7 ± 15.3
40.1 ± 11.8 41.0 ± 12.9 43.0 ± 12.6
29.3 ± 10.0 26.1 ± 14.8 30.9 ± 17.1
17.0 ± 4.4 22.2 ± 7.9 15.4 ± 7.4**
P < 0.05 for Magventure® vs Deymed® /MagStim® . P < 0.05 for Magventure® vs MagStim® .
Discussion In this paper we compared three different machines with respect to TMS-induced potentials and artifacts in EEG/EMG. We found that stimulation with the Magventure® device resulted in higher magnetic field strength, lower resting motor threshold, shorter duration of the magnetic field, shorter recovery time from the TMS-induced artifact, shorter latency of the MEPs, and reversed first artifact trajectory in contrast to the MagStim® and the Deymed® systems. At the same time, baseline activity was noisier with the Magventure® system as compared to the other two. There were no differences with respect to validity of the MEPs (number of kept values), MEP amplitudes (mean, CV), latency or amplitude of the second TMS artifact, or latency or amplitude of the TEPs. Five out of six subjects reported spontaneous tingling in their nose for the Deymed® system, but no one reported this for the other machines. The tingling sensation attributed to only the Deymed® system is unexpected since the physical and neurophysiological parameters are not different from the MagStim® system (coil size, pulse length, etc.). In our experience with TMS, over the last 10 years, tingling in the nose does also occur with the Magventure® and MagStim® system, but only in very rare cases. It is normal to have a sensory response to TMS under the coil or a muscle twitch in the muscle partly covered by the coil. The tingling specifically could potentially be due to cranial nerve stimulation, muscle stimulation of the frontalis muscle, or alternatively to the stimulation of the nose area of the sensory homunculus, which is considered to be not far from the index finger [30]. However at the current stage we have no explanation why this tingling sensation occurred much more frequently with the Deymed® system as compared to the other devices. The Magventure® system differed from the other machines with respect to higher field strength and lower motor threshold. We cannot exclude that this difference is related to the use of a smaller coil diameter for the Magventure® system (65 vs 70 mm), but we consider this
highly unlikely. First, earlier studies which compared motor and phosphene thresholds also found higher efficacy of the Magventure® system in contrast to the MagStim® system for coils with the same diameter [27]. Second a study comparing motor threshold between coil diameter of 50 and 70 mm in a MagStim® system could not find differences between the two coils [25]. The lower motor threshold, obtained with the Magventure® system, was a direct consequence of the higher field strength, since we could demonstrate that the magnetic field strength at motor cortex was similar for all three devices (see Fig. 1). It also seems unlikely that differences in the coil size led to the observed differences in the strength of the magnetic field, the TMS artifact latency (recovery time), or the MEP latency. There are studies showing that there is no difference in motor response between mono- and biphasic stimulators [20], between a butterfly and H-coil [6], or between a round and butterfly coil [5]. One possibility is that the shorter MEP latency might be related to our finding of a shortened duration of the magnetic field. The open question is how the shorter magnetic field duration of 60 s results in a shortening of the MEP latency of 1 ms. One would have to assume that small differences in the pulse length are accumulated in the motor system with a 10-fold factor measurable by an elongation on a peripheral physiological level. Another potential explanation could be that the observed differences in the pulse configuration (upstroke followed by a downstroke or vice versa) could interfere with the MEP latency. A reversed pulse configuration might explain the difference in the trajectory of the first TMS artifact for the Magventure® in contrast to the MagStim® and the Deymed® systems. Coil orientation is important to direct current flow; inverse current flow is comparable to a coil rotation by 180◦ . Changes in both current flow and orientation have been found to influence MEP amplitudes [11]. We were not able to measure the pulse configuration with our equipment but the inversed first artifact trajectory indirectly affirms this consideration. The elongation of the recovery time might also be related to a longer magnetic field or alternatively could be an
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TMS-EEG artifacts artifact resulting from the used definition of recovery time (3 × SD of baseline). A noisy baseline greatly influences this calculation and may have confounded our finding of the shorter recovery time of the Magventure® system. The amplitudes of the baseline were statistically different for the Magventure® system. This is potentially due to the increased line noise found for this amplifier. When looking at the first TMS-induced artifacts, the difference in the trajectory between the Magventure® and the other two systems is not evident in the trajectory of the secondary artifact or the TEP and as such should have little effect on the signals of interest after the recovery period, which we found to be less than 8 ms for all machines. Rogasch et al. [19] and Mutanen et al. [16] suggested that the secondary artifact is most likely a result of muscular stimulation and the TEPs of neural origin. This explanation would fit with our finding that the second artifact and the TEPs do not have reversed polarity between the machines in contrast to the technically-induced first artifact. The reproducibility of two well-recognized peaks, the P60 and the N100, following TMS stimulation suggests that neural stimulation was successful. TEPs were comparable between machines with respect to latency and amplitude. However, the CV of the amplitude was different (Magventure® vs MagStim® /Deymed® ) which might be related to the line noise only visible for the Magventure® system. We assume that line noise should be cancelled out by the manual triggering which means that the TMS pulses were not given with a fixed but with a variable inter-pulse interval. The line noise might be related to the positioning of the TMS machine in relation to the EEG system as the Magventure® system was located more proximal to the EEG amplifier. In conclusion, our comparison of TMS machines found that the Magventure® device differs from the Deymed® and MagStim® devices in strength and duration of the magnetic pulse, and also in MEP latency and CV of the TEPs amplitude. In addition, the combination of the Magventure® and Brain Products system was accompanied with line noise resulting in lower data quality and putatively an influence on recovery time. However, MEPs and TEPs were detectable for all machines and amplitudes were comparable for all three machines by using stimulation intensity adjusted to the individual motor threshold. This finding confirms that adjustment of the stimulation intensity according to individual motor threshold seems to be an effective method to obtain comparable MEP and TEP amplitudes with different stimulation devices. Unexpectedly the Deymed® system elicited additional side effects (tingling in the nose), which may be indicative of further technical differences between the devices. Based on this evidence, we suggest that all of these devices are well suited for TMS-EEG measurements, but the technical differences should be taken into account for the interpretation of the results of these experiments.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
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Acknowledgements The authors would like to thank Magventure® A/S and Dr. Langer Medical for the TMS equipment and the skilled technical and methodical support.
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TMS-related potentials and artifacts in combined TMS-EEG measurements: Comparison of three different TMS devices Gestion des artefacts lors de la mesure des potentiels liés à la stimulation magnétique transcrânienne (SMT) lors des enregistrements combinés EEG-SMT : comparaison de trois systèmes J. Van Doren , B. Langguth , M. Schecklmann ∗ University of Regensburg, Department of Psychiatry and Psychotherapy, Universitaetsstrasse 84, 93053 Regensburg, Germany Received 11 September 2014; accepted 15 February 2015
KEYWORDS Transcranial magnetic stimulation; Electroencephalography; Artifact; Evoked potential; Magnetic field
∗
Summary Objectives. — Simultaneous use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) allows the measurement of TMS-induced cortical activity. A challenge in the interpretation of the cortical responses to TMS pulses is the differentiation between stimulation artifacts and cortical signals. Thus, we investigated TMS-evoked potentials and artifacts with respect to different TMS devices. Methods. — Physical properties of the magnetic field produced by a MagStim® , Magventure® and Deymed® stimulator were determined. Six subjects were stimulated over the left motor cortex hot spot of the right index finger 42 times with 120% motor threshold, while wearing a 60-electrode EEG cap. Results. — For each device we found a linear increase of field strength with a linear increase of machine output. The Magventure® system differed from the MagStim® and the Deymed® system with respect to field strength (higher), magnetic flux duration (shorter), motor threshold (lower), recovery time from the TMS artifact (shorter), motor evoked potentials (MEPs) latency (shorter), and had a reversed first artifact trajectory. There were no differences with respect to validity of the MEPs (number of valid epochs), MEP amplitudes, latency or amplitude of the second TMS artifact, or latency or amplitude of TMS-evoked potentials (TEPs).
Corresponding author. Tel.: +49 941 941 2054; fax: +49 941 941 2065. E-mail address: [email protected] (M. Schecklmann).
http://dx.doi.org/10.1016/j.neucli.2015.02.002 0987-7053/© 2015 Elsevier Masson SAS. All rights reserved.
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J. Van Doren et al. Conclusions. — All of the used devices are well suited for TMS-EEG measurements, but the technical differences (e.g., pulse length) should be taken into account for the interpretation of the results of these experiments. Our results further confirm that adjustment of the stimulation intensity according to individual motor threshold seems to be an effective method to obtain comparable MEP and TEP amplitudes with different stimulation devices. © 2015 Elsevier Masson SAS. All rights reserved.
MOTS CLÉS Stimulation magnétique transcrânienne ; Électroencéphalographie ; Artefact ; Potentiels évoqués ; Champ magnétique
Résumé But de l’étude. — L’enregistrement de l’EEG au cours de la stimulation magnétique transcrânienne (SMT) permet la mesure de potentiels liés à la SMT. L’interprétation de ceux-ci se heurte à la difficulté de différencier les artefacts de stimulation et les réponses d’origine cérébrale. Trois systèmes d’enregistrement ont été comparés par rapport à ce problème. Méthodes. — Nous avons déterminé les propriétés physiques des champs magnétiques produits par les stimulateurs MagStim® , Magventure® et Deymed® . Six sujets porteurs d’un casque EEG à 60 électrodes ont été stimulés à 42 reprises en regard de l’aire de représentation de l’index droit, à 120 % du seuil moteur. Résultats. — Pour chaque système, l’intensité du champ a augmenté linéairement en fonction de la sortie annoncée du stimulateur. Le système Magventure® se différenciait des deux autres sur base de l’intensité du champ (plus élevée), de la durée du flux magnétique (plus courte), du seuil moteur (plus faible), du temps de récupération de l’artefact (plus court), du temps de latence du potentiel moteur (plus court) ; il montrait de surcroît une inversion de la première partie de l’artefact. Par contre, aucune différence ne fut constatée au niveau du nombre d’époques acceptables, des amplitudes des potentiels moteurs, du temps de latence ou de l’amplitude du second artefact ou du temps de latence ou de l’amplitude des potentiels liés à la SMT. Conclusions. — Alors que tous les systèmes étudiés sont bien adaptés aux enregistrements simultanés EEG-SMT, des différences techniques doivent être prises en compte en vue de l’interprétation des résultats. Nos résultats confirment que l’ajustement de la puissance de stimulation sur base des seuils moteurs individuels constitue la meilleure garantie d’obtention de potentiels moteurs ou liés à la SMT comparables lorsqu’ils ont été obtenus au moyen de systèmes de stimulation différents. © 2015 Elsevier Masson SAS. Tous droits réservés.
Introduction Transcranial magnetic stimulation (TMS) is a tool for noninvasive stimulation of the brain that is widely being used to study healthy and diseased cortical function [22]. It is additionally being developed as a therapeutic intervention in neuro-psychiatric disorders such as schizophrenia [1], depression [8], and tinnitus [13] and is being explored as possible technique for the enhancement of cognitive functions [15]. In summary, effect sizes for these approaches are small to moderate. To enhance the efficacy of TMS, it is necessary to increase the knowledge about the exact neurophysiological mechanism of TMS over the various brain regions. For this, combined measurements of TMS and electroencephalography (EEG) are highly recommended since EEG can measure fast TMS-induced neural activity with high temporal resolution. The challenge is to differentiate the neural response to TMS from the relatively large artifacts created by the TMS pulse. Many techniques have been suggested for the minimization of this artifact, such as good electrode impedance (< 5k), not stimulating over highly muscular areas (stick to the midline), avoiding auditory and startle reflex artifacts by using earplugs and/or masking, and avoiding somatosensory artifacts by dampening the coil vibration on the head by using foam [9,16,23,28]. In addition, hardware modification
and a variety of offline data analyses have been suggested to improve the quality of data [7,26,29,10]. The TMS artifact is characterized as a sharp first peak starting at the time of stimulation and lasting 5 ms [28] followed by a second artifact occurring around 5—10 ms post-stimulation [19]. The first artifact is attributable to the electrical charge generated by the TMS pulse, while the second is thought to be of muscular origin [19]. This first artifact is to distinguish from a later artifact in some types of machines generated by the recharging of the TMS device. The signals of interest for stimulation of the motor cortex are motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs). Both are well characterized and are considered valid measurements of the effect of the TMS pulse on the brain. The MEP is a biphasic, evoked activity with a specific latency that is detected by electromyography in the corresponding muscle of the stimulated homunculus area. It is the result of the net activation of the motor cortex, propagated via activation of pyramidal cells and the cortico-spinal tract, with a specific conductance time to the muscle in the periphery. The TEPs are EEG-evoked potentials with various peaks including the P60 and the N100 [19,2,14]. The P60 is thought to be a signal that is evoked from the sulci of the primary motor cortex and reflective of inhibition [12], whereas the N100 has been described as a neural correlate of inhibition and associated to attention [3,17]. Both peaks additionally
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TMS-EEG artifacts have been suggested to reflect a resetting effect of the TMS pulse on the oscillatory activity of the brain [18]. Only recently TMS-induced artifacts and -evoked potentials produced by different TMS machines have been compared and have been found to be highly reproducible [19]. However, it is known that differences in technical parameters (e.g., pulse duration and form) can influence the induced activity in the brain [21,24] and TMS machines from different manufacturers may vary in the time course, the spatial distribution and the maximum strength of the induced magnetic field. Thus, the purpose of this study is to compare and characterize the signal (MEPs and TEPs) and artifacts (first and second artifacts) in combined TMS-EEG measurements using two common (Magventure® Magpro, Magventure® , Denmark; MagStim® Rapid, MagStim® Co. LTD, United Kingdom) and one novel TMS machine (Deymed® DuoMag XT-100, Deymed® Diagnostic, Czech Republic). First, we characterized maximal strength and duration of the induced magnetic field at different stimulation intensities. Second, we measured the TMS associated first and second artifacts, motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) in six healthy subjects.
Methods Sample and procedures Six healthy students (4 female; 24.6 ± 2.3 years) from the University of Regensburg participated in this study after providing written informed consent. The study was approved by the local ethics committee of the University of Regensburg. All participants had no previous or present severe somatic, neurological, or psychiatric problems. Participants were comfortably seated in a clinical armchair for the duration of the experiment. First, the resting motor threshold was obtained for each machine with the electrode cap on the head. Second, the impedances were lowered to below 5 k. Third, the stimulation took place with a balanced order of the machines, which was randomized to the single participants. For the TMS-EEG measurement, subjects were instructed to sit as still as possible with eyes closed and TMS clicks were masked with white noise applied via insert earplugs. Field strength and duration measurements of the TMS pulses were performed in separate sessions.
Magnetic field To determine if there were possible differences between machine outputs, we tested the magnetic field strength of each machine using a 475 DSP Gaussmeter with a HMMT6J18-VR probe (Lakeshore Inc., USA). The probe was taped to and aligned with the center of the coil. Measurements were made in triplicate for each machine at 30, 35, 40, 45, 50, 55, 60, 70, 80, 90, and 100% of the machine intensity. Additionally, the duration of the magnetic field was measured by the voltage change induced in a wire loop with a diameter of 2 cm placed in the center of the coil. All stimulation devices produced biphasic stimuli. The biphasic magnetic field has the form of a sine wave and the voltage change is calculated by the temporal derivation of
3 the magnetic field (U = −˚/t; U = voltage; ˚ = magnetic flux; t = time; = difference). The voltage change is indicated by a cosine wave, which was present for all three stimulators. Duration of the magnetic field was indicated by return of the voltage change to baseline. For measurement of the voltage change we used a Tektronix TDS 1002 oscilloscope (Tektronix Inc., USA).
Transcranial magnetic stimulation TMS was applied with three different TMS machines and figure of eight coils (see Table 1). The coil was held at a 45-degree angle to the mid-sagittal line with the handle pointing backwards. The motor hotspot was determined by placing the center of the coil over C3 as the starting point and adjusting the coil until the highest motor-evoked potential was reliably obtained from the right first dorsal interosseous muscle. For five subjects the hotspot was in close proximity to C3; for one participant it was localized near C1. Hotspot and orientation of the coils were comparable over the three devices. The resting motor threshold defined as the lowest threshold at which a motor potential was obtained with an amplitude of at least 50 V in four out of eight stimulations [20] was determined for each machine individually and the stimulation intensity was 120% of each individual threshold. For each machine, 42 pulses spaced about 5 seconds apart were triggered manually.
Electrophysiological measurements For EEG and EMG, we used a BrainAmp amplifier (Brain Products GmbH, Germany) with TMS compatible Ag/AgCl sintered pin electrodes (EASYCAP GmbH, Germany). For the EEG measurement, 60 head electrodes with the reference over FCz and the ground over AFz were used according to the international 10-10 EEG system. For determination of the motor-evoked potentials two Ag/AgCl sintered ring electrodes were placed on the right first dorsal interosseous muscle in a tendon belly montage. Signals were recorded with BrainVision Recorder 1.2 with a sampling rate of 5000 Hz using a DC low cut-off and a high cut-off filter of 1000 Hz.
Data and statistical analysis EEG analysis was performed using Brain Vision Analyzer 1.0 (Brain Products, Germany) and the EEGLAB toolbox [4] made for Matlab 2012 (MathWorks Inc., USA). Triggers were placed manually using Brain Vision Analyzer at the first point of deviation from baseline activity near the TMS-induced artifact. These markers were used for further analysis as artifact onset. The EMG data was analyzed using a bipolar montage. The EEG data was first re-referenced to an average reference and then segmented from one second before to one second after the trigger point. Baseline correction was applied from —500 ms to —110 ms according to Rogasch et al. [19]. No filtering of the signal was used. Trials that did not produce a clear MEP (biphasic trajectory) were excluded from further analysis. Analysis was performed using the motor hotspot electrode for each participant (C3 for 5 participants and C1 for one participant). The second artifact, TEPs and MEPs were analyzed both for minimum and maximum peaks as elicited by peak detection algorithms in Vision
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J. Van Doren et al. Table 1
Technical information regarding the used TMS systems.
TMS machine
Company, location
Pulse length (s)a
Diameter of coil (mm)
Coil name
Pulse typea
Magventure® Magpro MagStim® Rapid Deymed® DuoMag XT-100
Magventure® , Denmark MagStim® Co. LTD, United Kingdom Deymed® Diagnostic, Czech Republic
320
65
MCF-B65
Biphasic
380
70
D70-alpha
Biphasic
380
70
70-BF
Biphasic
a
As elicited by own measurements.
Analyzer. All segments were visually inspected for the accuracy of the peak detection and adjusted accordingly. In the EEG, one positive and one negative peak were found from 4—12 ms for the second artifact and from 30 to 160 ms for the TEPs (P60 and N100). In the electromyogram the period from 20 to 50 ms was inspected for the MEPs. Latency was defined as the latency of the first maximum/minimum. This method was chosen in analogy to the peak detection of the TEPs. Amplitude was analyzed with respect to the peak-to-peak amplitude difference between the positive and negative peak. Dependent variables (TMS artifacts, TEPs, MEPs) were evaluated for both individual participant trials and averaged for individual participants. The individual averages were then used for statistical analysis. Recovery time from the TMS pulse was assessed according to Rogasch et al. [19]. First, we calculated the standard deviation of the baseline multiplied by three, which is considered to be representative of common resting state EEG activity. Second, data bins were categorized to fall outside or inside of this value starting at the trigger. The time in which the data moved from outside to inside of this common resting state activity is defined as the recovery time from the TMS artifact. In addition to the mean values, we calculated the coefficient of variation (CV) as an indicator for variability. CV is defined by the standardization of the standard deviation (SD) to the individual mean value ((SD/mean) × 100). CV was calculated for amplitude measures of the MEPs, the second TMS artifacts, and the TEPs. The first artifact was not statistically assessed due to saturation effects in the majority of segments. Statistical analysis was performed using SPSS 21.0 (IBM, Armonk, New York, USA). Due to small sample size, we used non-parametric statistics such as the Friedman test (comparison of all machines) and the Wilcoxon signed-rank test (post-hoc test in the case of a significant Friedman test) to compare differences between the machines. Significance threshold was set to 5%. Raw data are depicted as mean ± standard deviation if not otherwise stated.
Results Side effects The only reported side effect for all machines was sensation on the scalp and muscle below the coils. During stimulation
Figure 1 Magnetic field strength values (max: maximum positive value; min: minimum negative value; please note that the pulse is biphasic, producing positive and negative values).
with the Deymed® system, five out of six subjects reported tingling in the nose. For the other devices no such sensation was reported.
Magnetic field strength Magnetic field strength was found to increase linearly for all three machines with differences in the strength of the magnetic field (see Fig. 1). The Magventure® device induced the strongest field with small differences in the positive values between the MagStim® and the Deymed® system. Duration of the magnetic field as elicited by voltage changes was about 320 s for Magventure® and 380 s for the MagStim® and Deymed® machines.
Motor threshold (MT) The motor threshold (Deymed® : 55.7% ± 6.1 (2.7 T); MagStim® : 55.3% ± 6.1 (2.8 T); Magventure® : 48.0% ± 5.6 (2.78 T)) was significantly different between the machines (P = 0.006). The Magventure® differed from the MagStim® (P = 0.027) and the Deymed® system (P = 0.027); the
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MagStim® and the Deymed® system (P = 0.577) did not differ. We derived the magnetic field strength values corresponding to the mean motor threshold for each machine from Fig. 1 (values in brackets above) indicating that the magnetic field strength is comparable over the machines despite differences in MT.
Motor-evoked potentials (MEP) Before analysis, segments were visually inspected for valid MEP trajectories. The number of kept segments (Deymed® = 82.3%; MagStim® = 81.7%; Magventure® : 75.0%) was not statistically different between the machines (P = 0.846). MEPs did vary in latency, as indicated by the first peak of the MEP, between Magventure® and the other machines (P = 0.011; Deymed® = 27.7 ± 2.5 ms; MagStim® = 27.6 ± 2.7 ms; Magventure® = 26.8 ± 2.3 ms) in which the Magventure® machine elicited MEPs slightly faster than the Deymed® (P = .028) and MagStim® (P = .028) machines, while Deymed® and MagStim® did not differ from each other (P = 0.600). However there was no difference in amplitude on average (P = 0.607) or variability level of the peak-to-peak amplitude (P = 0.607; CV: Deymed® : 56.2% ± 23.1; MagStim® : 61.6% ± 14.4; Magventure® : 54.8% ± 13.7).
Figure 2 Second artifact grand average values (max: maximum positive value; min: minimum negative value).
TMS artifacts The first artifact for the MagStim® and the Deymed® system was characterized in the grand averaged data by a sharp negative peak after TMS stimulation followed by a large positive peak within 2 ms after the TMS pulse onset. The peaks created by the Magventure® system were similar in latency, but began instead with a sharp positive peak followed by a negative peak. The second artifact for all three machines was characterized by a positive peak around 5 ms after TMS stimulation and a negative peak around 8 ms. There was no difference between machines in relation to latency (P = 0.350) or peak-to-peak amplitude difference score (P = 0.513). CV for the amplitude difference was not significant between the machines (P = 0.607; Deymed® : 16.4% ± 7.1; MagStim® : 22.4% ± 9.3; Magventure® : 27.7% ± 15.3). For details see Table 2 and Fig. 2. Recovery time varied significantly between the machines (P = 0.009; Deymed® : 6.9 ms ± 1.1; MagStim® : 7.0 ms ± 1.0; Magventure® : 6.0 ms ± 0.9). The recovery time of the Magventure® device was significantly shorter than for the Deymed® (P = 0.028) and the MagStim® (P = 0.028) systems. CV of recovery time was not significantly different (P > 0.999; Deymed® : 3.07% ± 1.7; MagStim® : 4.02% ± 3.2; Magventure® : 8.02% ± 7.0). Baseline activity was additionally significantly different for the Magventure® system (P = 0.011; Deymed® : 4.35 V ± 1.6; MagStim® : 4.2 V ± 1.6; Magventure® : 9.1 V ± 1.7) compared to the Deymed® (P = 0.028) and MagStim® (P = 0.028) systems, while Deymed® and MagStim® did not differ from one another (P = 0.753).
Figure 3 TEP grand average (P60 and N100 indicated TMSevoked potentials).
TMS-evoked potentials All machines elicited a similar pattern of peaks; a P60 and N100 were apparent (see Fig. 3). The latency (P = 0.223) and amplitude difference score (P = 0.223) did not differ between machines. However, the CV of the amplitude difference score differed between the machines (P = 0.042). The Magventure® CV was significantly different than that of the MagStim® machine (P = 0.028), but not the Deymed® (P = 0.345). The Deymed® and MagStim® machines did not differ (P = 0.463). The CV values for each machine: Deymed® = 17.0% ± 4.4, MagStim® = 22.2% ± 7.9, Magventure® = 15.4% ± 7.4. The Magventure® system was noisier than the other two, as seen by line noise. This artifact was seen in all channels, not only those under the coil.
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J. Van Doren et al. Table 2 Mean latency of the first peak, amplitude difference of the first and second peak and coefficient of variation (CV) of the amplitude difference for motor-evoked potentials (MEP), second artifact, and TMS-evoked potentials (TEP).
MEP Deymed® MagStim® Magventure® Second artifact Deymed® MagStim® Magventure® TEP Deymed® MagStim® Magventure® * **
Latency first peak (ms)
Amplitude difference (V)
CV of amplitude difference (%)
27.7 ± 2.5 27.6 ± 2.7 26.8 ± 2.3*
1346.5 ± 1377.8 1190.0 ± 1247.4 1228.9 ± 945.7
56.2 ± 23.1 61.6 ± 14.4 54.8 ± 13.7
5.3 ± 0.7 5.3 ± 0.3 5.1 ± .2
333.8 ± 248.0 234.12 ± 188.2 396.0 ± 237.00
16.4 ± 7.1 22.4 ± 9.3 27.7 ± 15.3
40.1 ± 11.8 41.0 ± 12.9 43.0 ± 12.6
29.3 ± 10.0 26.1 ± 14.8 30.9 ± 17.1
17.0 ± 4.4 22.2 ± 7.9 15.4 ± 7.4**
P < 0.05 for Magventure® vs Deymed® /MagStim® . P < 0.05 for Magventure® vs MagStim® .
Discussion In this paper we compared three different machines with respect to TMS-induced potentials and artifacts in EEG/EMG. We found that stimulation with the Magventure® device resulted in higher magnetic field strength, lower resting motor threshold, shorter duration of the magnetic field, shorter recovery time from the TMS-induced artifact, shorter latency of the MEPs, and reversed first artifact trajectory in contrast to the MagStim® and the Deymed® systems. At the same time, baseline activity was noisier with the Magventure® system as compared to the other two. There were no differences with respect to validity of the MEPs (number of kept values), MEP amplitudes (mean, CV), latency or amplitude of the second TMS artifact, or latency or amplitude of the TEPs. Five out of six subjects reported spontaneous tingling in their nose for the Deymed® system, but no one reported this for the other machines. The tingling sensation attributed to only the Deymed® system is unexpected since the physical and neurophysiological parameters are not different from the MagStim® system (coil size, pulse length, etc.). In our experience with TMS, over the last 10 years, tingling in the nose does also occur with the Magventure® and MagStim® system, but only in very rare cases. It is normal to have a sensory response to TMS under the coil or a muscle twitch in the muscle partly covered by the coil. The tingling specifically could potentially be due to cranial nerve stimulation, muscle stimulation of the frontalis muscle, or alternatively to the stimulation of the nose area of the sensory homunculus, which is considered to be not far from the index finger [30]. However at the current stage we have no explanation why this tingling sensation occurred much more frequently with the Deymed® system as compared to the other devices. The Magventure® system differed from the other machines with respect to higher field strength and lower motor threshold. We cannot exclude that this difference is related to the use of a smaller coil diameter for the Magventure® system (65 vs 70 mm), but we consider this
highly unlikely. First, earlier studies which compared motor and phosphene thresholds also found higher efficacy of the Magventure® system in contrast to the MagStim® system for coils with the same diameter [27]. Second a study comparing motor threshold between coil diameter of 50 and 70 mm in a MagStim® system could not find differences between the two coils [25]. The lower motor threshold, obtained with the Magventure® system, was a direct consequence of the higher field strength, since we could demonstrate that the magnetic field strength at motor cortex was similar for all three devices (see Fig. 1). It also seems unlikely that differences in the coil size led to the observed differences in the strength of the magnetic field, the TMS artifact latency (recovery time), or the MEP latency. There are studies showing that there is no difference in motor response between mono- and biphasic stimulators [20], between a butterfly and H-coil [6], or between a round and butterfly coil [5]. One possibility is that the shorter MEP latency might be related to our finding of a shortened duration of the magnetic field. The open question is how the shorter magnetic field duration of 60 s results in a shortening of the MEP latency of 1 ms. One would have to assume that small differences in the pulse length are accumulated in the motor system with a 10-fold factor measurable by an elongation on a peripheral physiological level. Another potential explanation could be that the observed differences in the pulse configuration (upstroke followed by a downstroke or vice versa) could interfere with the MEP latency. A reversed pulse configuration might explain the difference in the trajectory of the first TMS artifact for the Magventure® in contrast to the MagStim® and the Deymed® systems. Coil orientation is important to direct current flow; inverse current flow is comparable to a coil rotation by 180◦ . Changes in both current flow and orientation have been found to influence MEP amplitudes [11]. We were not able to measure the pulse configuration with our equipment but the inversed first artifact trajectory indirectly affirms this consideration. The elongation of the recovery time might also be related to a longer magnetic field or alternatively could be an
Please cite this article in press as: Van Doren J, et al. TMS-related potentials and artifacts in combined TMS-EEG measurements: Comparison of three different TMS devices. Neurophysiologie Clinique/Clinical Neurophysiology (2015), http://dx.doi.org/10.1016/j.neucli.2015.02.002
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TMS-EEG artifacts artifact resulting from the used definition of recovery time (3 × SD of baseline). A noisy baseline greatly influences this calculation and may have confounded our finding of the shorter recovery time of the Magventure® system. The amplitudes of the baseline were statistically different for the Magventure® system. This is potentially due to the increased line noise found for this amplifier. When looking at the first TMS-induced artifacts, the difference in the trajectory between the Magventure® and the other two systems is not evident in the trajectory of the secondary artifact or the TEP and as such should have little effect on the signals of interest after the recovery period, which we found to be less than 8 ms for all machines. Rogasch et al. [19] and Mutanen et al. [16] suggested that the secondary artifact is most likely a result of muscular stimulation and the TEPs of neural origin. This explanation would fit with our finding that the second artifact and the TEPs do not have reversed polarity between the machines in contrast to the technically-induced first artifact. The reproducibility of two well-recognized peaks, the P60 and the N100, following TMS stimulation suggests that neural stimulation was successful. TEPs were comparable between machines with respect to latency and amplitude. However, the CV of the amplitude was different (Magventure® vs MagStim® /Deymed® ) which might be related to the line noise only visible for the Magventure® system. We assume that line noise should be cancelled out by the manual triggering which means that the TMS pulses were not given with a fixed but with a variable inter-pulse interval. The line noise might be related to the positioning of the TMS machine in relation to the EEG system as the Magventure® system was located more proximal to the EEG amplifier. In conclusion, our comparison of TMS machines found that the Magventure® device differs from the Deymed® and MagStim® devices in strength and duration of the magnetic pulse, and also in MEP latency and CV of the TEPs amplitude. In addition, the combination of the Magventure® and Brain Products system was accompanied with line noise resulting in lower data quality and putatively an influence on recovery time. However, MEPs and TEPs were detectable for all machines and amplitudes were comparable for all three machines by using stimulation intensity adjusted to the individual motor threshold. This finding confirms that adjustment of the stimulation intensity according to individual motor threshold seems to be an effective method to obtain comparable MEP and TEP amplitudes with different stimulation devices. Unexpectedly the Deymed® system elicited additional side effects (tingling in the nose), which may be indicative of further technical differences between the devices. Based on this evidence, we suggest that all of these devices are well suited for TMS-EEG measurements, but the technical differences should be taken into account for the interpretation of the results of these experiments.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
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Acknowledgements The authors would like to thank Magventure® A/S and Dr. Langer Medical for the TMS equipment and the skilled technical and methodical support.
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