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    Marked differences in the thermal characteristics of figure-of ... Marked differences in the thermal characteristics of figure-of ... Document Transcript

    • Clinical Neurophysiology 116 (2005) 1477–1486 www.elsevier.com/locate/clinph Marked differences in the thermal characteristics of figure-of-eight shaped coils used for repetitive transcranial magnetic stimulation Thomas Weyha, Kerstin Wendickea, Claudia Mentschelb, Hannes Zantowa, Hartwig R. Siebnerb,c,d,* a ¨ ¨ ¨ Heinz Nixdorf-Lehrstuhl fur Medizinische Elektronik, Technische Universitat Munchen, Arcisstrasse 21, 80333 Munich, Germany b ¨ ¨ Department of Neurology, Technische Universitat Munchen, Moehlstrasse 28, 81675 Munich, Germany c Department of Neurology, Christian-Albrechts-University, Niemannsweg 147, 24105 Kiel, Germany d ¨ NeuroImageNord Hamburg-Kiel-Lubeck, Martinistrasse 52, 20246 Hamburg, Germany Accepted 9 February 2005 Available online 26 March 2005 Abstract Objective: To compare the heating behaviour of three figure-of-eight shaped coils during repetitive transcranial magnetic stimulation (rTMS). Methods: A custom-made coil (referred to as test coil) with a resistance-optimized conductor geometry was compared with two commercially available eight-shaped coils. Each coil was attached to the same energy source, which generated trains of 50 biphasic magnetic pulses every 20 s. Coil temperature was continuously measured during nine rTMS protocols using various combinations of stimulus frequencies (5, 10 or 20 Hz) and intensities (40, 50 or 60% of maximum stimulator output). A heating curve relating coil temperature and the number of applied stimuli was generated for each coil and rTMS condition. In eleven healthy volunteers, we evaluated the effectiveness of motor cortex stimulation. For each coil, we determined the motor threshold (MT) in the right first dorsal interosseus muscle. Results: The slope of the heating curves of the test coil was markedly flattened relative to the heating curves of the two standard coils. This allowed the application of at least twice as many stimuli until the temperature of the coil reached 40 8C. Based on these data, we showed that a one-mass model could be used to accurately describe the heating behaviour of each coil. MTs determined with the test coil were comparable to or lower than the MTs that were determined with the standard coils. Conclusions: The efficacy of the test coil to stimulate the M1 was comparable to the efficacy of the two standard coils, yet thermal characteristics were markedly improved. Significance: Overheating of figure-of-eight shaped coils can be markedly delayed without reducing the efficacy of rTMS. q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Coil temperature; Efficacy; Figure-of-eight coil; Motor threshold; Overheating; Repetitive transcranial magnetic stimulation 1. Introduction connected to a high-voltage, high-current discharge system which produces a strong magnetic field around the Since its introduction in 1985 (Barker et al., 1985), transducing coil for up to a few 100 ms (Barker, 1999). transcranial magnetic stimulation (TMS) has emerged as a When the coil is placed on the scalp, the induced magnetic safe and painless method for stimulating the human cortex field passes without attenuation through the skull and through the intact scalp (Maccabee et al., 1991; Rothwell induces an electrical current in the brain (Barker et al., et al., 1999). A device for TMS consists of a transducing coil 1985). The induced electrical current can excite cortical neurons depending on the intensity of stimulation. The introduction of stimulating devices that can * Corresponding author. Address: Department of Neurology, Christian- Albrechts-University, Niemannsweg 147, 24105 Kiel, Germany. Tel.: C49 produce trains of magnetic stimuli at rates up to 50 Hz 431 597 2703; fax: C49 431 597 2712. has considerably expanded the applications of TMS, E-mail address: h.siebner@neurologie.uni-kiel.de (H.R. Siebner). since repetitive transcranial magnetic stimulation 1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2005.02.002
    • 1478 T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 (rTMS) can induce lasting changes in cortical excit- The first standard coil used for comparison was the ability and function (Hallett et al., 1999). This has ‘Double 70 mm—Coil, Type P/N 9925’ which is provided opened up unprecedented possibilities to investigate by Magstim Company (Whitland, Dyfed, UK; www. regional cortical plasticity in health and disease (Siebner magstim.com). The surface of this figure-of-eight shaped and Rothwell, 2003). Preliminary evidence also suggests coil (referred to as ‘Magstim coil’) was flat and the two that rTMS may be used to temporarily improve brain windings had a diameter of 56–91 mm (mean diameter: function in neuropsychiatric disorders (George et al., 74 mm). The second standard coil included in the 1999; Siebner et al., 1999a,b; Wassermann and Lisanby, comparison was the ‘MC-B70 Butterfly Coil, Type 2001). MC-B70’ provided by Medtronic-NeuroMuscular For TMS, the stimulating coil should be highly (Skovlunde, Denmark, www.medtronic.com). This figure- efficient in order to produce maximal neuronal response of-eight shaped coil (referred to as ‘Medtronic coil’) had a at a given pulse energy. The stimulating coil should also slight bend and the turns in the centre of the coil were be highly focal, to minimize spread of excitation to other superimposed. The two windings had a diameter of cortical areas. Moreover, the discharge should produce 24–96 mm (mean diameter: 60 mm). minimal heat loss to avoid overheating during longer periods of TMS. So far, a figure-of-eight shaped coil 2.2. Experimental setup design (also referred to as butterfly coil) has mainly been used for rTMS. This coil produces the largest current To ensure comparability among measurements, all coils density in the tissue under its center with the largest were connected to the same energy source (MagPro component of the electric field being oriented in parallel Stimulator, Medtronic-neuromuscular, Skovlunde, to the wires in the center of the coil (Cohen et al., 1990; Denmark). This was possible because the magnetic Roth et al., 1991). This coil design results in a more stimulators constructed by Magstim Company and Med- focal stimulation of the underlying cortex than circular tronic-neuromuscular use capacitors of similar capaci- coils (Cohen and Cuffin, 1991; Yunokuchi and Cohen, tances. Therefore, both coils could be operated producing 1991). However, standard figure-of-eight shaped coils are the same pulse duration and configuration as designed by far from being optimal for rTMS. In particular, the the manufacturer. We designed and constructed an adapter temperature rise caused by resistive heating poses a which enabled us to attach the test and the Magstim coil to problem when longer periods of high-frequency rTMS the MagPro stimulator. This adapter also contained the are given. Here we compared the thermal characteristics electronics which evaluated the signals produced by the of two standard figure-of-eight coils and a newly temperature sensors in the test and Magstim coil. designed figure-of-eight coil with reduced internal Prior to the main experiment, we discharged the resistance. Our measurements revealed that coil heating capacitor of the MagPro stimulator through each coil. can be markedly reduced without affecting the effective- The intensity of stimulation was adjusted to 50% of ness of stimulation. maximum stimulator output. We measured the current direction and pulse duration induced in each coil with an arrangement of 3 orthogonal induction loops. The 2. Method pulse durations are given in Table 1. The inductance of the Medtronic coil was significantly smaller (Table 1). Because the pulse length is proportional to the square 2.1. Technical description of the figure-of-eight shaped coils root of the coil inductance, this results in a 10% decrease in pulse length relative to the other coils Table 1 summarizes the technical details of the three (Vachenauer, 1998). figure-of-eight coils tested in this study. The design of In an LCR circuit the potential differences across each the newly developed coil (referred to as ‘test coil’) is component are given by illustrated in Fig. 1. The test coil consisted of 4 planar coils on top of each other. The coils in layers 1 and 4 had 15 turns and the coils in layer 2 and 3 had 12 turns, 1 dU ðtÞ d2 UC ðtÞ UC ðtÞ C Ri C C L Z0 (1) respectively. The mean winding diameter of each coil C dt dt2 wing was 65 mm, ranging from 15 to 97 (layers 1 and 4) and 21 to 97 mm (layers 2 and 3). Accordingly, the where C is the stimulator’s capacitance, UC is the capacitors dimensions of the test coil was 190!97 mm. The voltage, L is the coil’s inductance and Ri is the sum of all conductors were made of high-frequency Litz wire. internal resistances. Each filament was isolated with lacquer. The Litz wires Assuming a small coil resistance Ri, the circuit is were isolated using Capton. The 4 coil layers were essentially an LC oscillator whose period (T) is given by: connected in parallel and thus were interspersed by the pffiffiffiffiffiffiffiffiffi same flux resulting in 4 equal inductances. T Z 2p L$C (2)
    • T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 1479 Table 1 Characteristics of the three figure-of-eight shaped coils which were compared in this study Name of coil (manufacturer) P/N 9925 coil (Magstim Company) MC-B70 coil (Medtronic) Custom-made coil No. of windings per half wing 9 turns 13 turns 12 turns (layers 2 and 3); 15 turns (layers 1 and 4) Mean winding diameter and range (mm) 60 (24–96) 74 (56–91) 65 (15/21–97) Inductance (mH) 15.51 12.17 14.98 Pulse duration (ms) 349 309 343 DC-resistance (mU) 8.00 8.20 6.30 AC-resistance (mU) 17.55 11.33 7.35 Thermal time constant (s) 2740 2892 3190 Thermal conductance (W/K) 0.390 0.390 0.384 The resistance values were measured at direct current (DC) and calculated for alternating current (AC) at the frequency of the sine wave produced by the stimulator. The capacitance of the stimulator was determined using of the current pulse with respect to the handle of the coil. the formula: Accordingly, a stimulus with the initial rising phase running  2 from the front towards the handle of the coil has a anterior- T 1 to-posterior (a-p) orientation, whereas a posterior-to- CZ (3) 2p L anterior (p-a) current orientation refers to a stimulus with the initial rising phase running from the handle towards the The inductance of the LC-oscillator (e.g. test coil front of the coil. LZ15.1 mH) resulted from the sum of the coil inductance (LCoilZ15.0 mH) and cable inductance (LCableZ0.1 mH). The period of a full wave (e.g. test coil TFull Wave- 2.3. Experiment 1: thermal measurements Z342.93 ms) was averaged over 14 individual measure- ments with a frequency-compensated voltage divider. Nine different combinations of stimulus frequencies According to the formula given above, the resulting (5, 10, or 20 Hz) and intensities (40, 50, or 60% of capacity of C was 197.3 mF. With the calculated capacitance maximum stimulator output) were chosen to test the thermal the inductances L of the two other coils (Magstim and characteristics of each coil (Table 2). In clinical studies, Medtronic) could be calculated. high-frequency rTMS is usually divided into trains of The apparatus used for measurements of inductance and stimuli separated by an inter-train interval of seconds or capacitance was a Precision Digital LCR Meter HP4274A minutes to ensure the safety of rTMS (Chen et al., 1997; (Hewlett-Packard, Palo Alto, USA) which has been George et al., 1999). In order to match our rTMS protocols specifically designed to measure capacities, inductivities to those applied in patients, we separated each rTMS train and internal resistances of the magnitude as generated in the by an inter-train interval of 20 s. A single train consisted of stimulating coil during TMS. 50 biphasic pulses. The coil was supported by a mechanical The current driven through the Magstim coil and the test coil holder and discharged in air. coil has an opposite direction compared with the Medtronic coil. When the Medtronic coil was discharged by the MagPro stimulator and current direction was set to ‘normal’, the first rising phase of the current pulse was directed from the handle towards the front end of the coil. By contrast, when the Magstim coil and the test coil were discharged by the MagPro stimulator via the custom-made adapter, the first rising phase of the current pulse was directed from the handle towards the front end of the coil Fig. 1. Geometric configuration of the newly designed ‘test’ coil. The coil when the ‘reversed’ current direction was selected. This consisted of 4 planar coils on top of each other (layer 1–4). The coils were connected in parallel. The coils in layers 1 and 4 had 15 turns and the coils reversal of current direction introduced by the adapter was in layer 2 and 3 had 12 turns, respectively. Each square corresponds to a taken into account in the main experiments. In the single turn. The mean winding diameter of each coil wing was 65 mm, remainder of the manuscript, specifications regarding the ranging from 15 to 97 (layers 1 and 4) and 21 to 97 mm (layers 2 and 3). current directions in the coil always refer to the initial phase Each halfwing had a diameter of 97 mm.
    • 1480 T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 Table 2 Settings of the nine rTMS protocols used to measure the heating of the figure-of-eight shaped coils TMS protocol (No.) 1 2 3 4 5 6 7 8 9 Intensity (maximum output in %) 40 40 40 50 50 50 60 60 60 Frequency (Hz) 5 10 20 5 10 20 5 10 20 Train duration (s) 10 5 2.5 10 5 2.5 10 5 2.5 Inter-train interval (s) 20 20 20 20 20 20 20 20 20 Pulse duration was measured using a MagPro stimulator and a full sine wave current. In the present study, magnetic stimuli had a biphasic 2.4. Experiment 2: threshold measurements pulse configuration because most rTMS protocols use biphasic stimuli. The term ‘biphasic stimulation’ is used We applied single-pulse TMS over the left primary by neurophysiologists when the stimulating coil is driven by motor hand area (M1) to compare the effectiveness of a full-wave sinus current, resulting in a reversal of current transcranial magnetic stimulation for the three figure-of- direction during the pulse. The reason behind the prefer- eight shaped coils. The effectiveness of stimulation was ential use of biphasic pulses for rTMS is that this pulse evaluated by measuring the threshold for evoking a motor configuration makes it possible to recover a substantial response in the right first dorsal interosseus (FDI) muscle. amount of the original energy for the next discharge The motor threshold (MT) was determined using biphasic (Barker, 1999). In addition, biphasic stimuli result in a magnetic stimuli at rest or during isometric contraction and more efficient stimulation of cortical neurones requiring less expressed as a percentage of maximum stimulator output. energy for effective stimulation (Barker, 1999). The orientation of the first phase was either anterior-to- Room temperature ranged between 20 and 25 8C. At the posterior (a-p) or posterior-to-anterior (p-a). beginning of each measurement, we made sure that the coil Eleven healthy volunteers (age 24–44 years, 2 females, 9 temperature matched the room temperature for at least males) participated in the experiment. All individuals gave 10 min. The threshold for overheating was set at a coil their written informed consent prior to the study. The temperature (as measured by the sensors) of 40 8C. experimental procedures were approved by the local Immediately after each rTMS train, temperature was Institutional Review Board. The technical safety of the measured using the temperature sensor integrated in test coil was approved according to the Medical Device the coil. rTMS was stopped when coil temperature had ¨ Regulation by the TUV Product Service Ltd (Munich, reached 40 8C. Temperature measurements were continued Germany). for 5–10 min after the end of rTMS. The experiment had a 3-factorial design with the factors Each coil has a build-in thermal sensor located near the ‘coil’ (3 levels: test coil, Magstim coil and Medtronic coil), conductors in the coils center. Medtronic-neuromuscular ‘motor state’ (two levels: rest versus contraction), and two uses an integrated circuit giving a proportional current of stimulus orientations (two levels: a-p orientation versus p-a 1 mA per centigrade. The Magstim coil and the test coil have orientation). Each participant underwent twelve measure- an integrated circuit (LM 35 DZ) which gives a proportional ments (4 measurements with the same coil). Within each voltage of 10 mV/8C. The position of each sensor was block, measurements at rest always preceded measurements identified by radiography. Radiograms revealed that the during contraction. The experiment lasted for approxi- locations of the thermal sensors were comparable among mately 1 h. coils. All sensors were located below the intersection of the At the beginning of each block, we determined the two wings. optimum position for activation of the right FDI muscle for For each measurement, we plotted the rise in each coil by moving the coil in 0.5 cm steps around the temperature against the number of magnetic stimuli, presumed M1. The site at which stimuli of slightly and created a heating curve for each coil at a given suprathreshold intensity consistently produced the largest intensity and frequency of rTMS. The maximum number motor response was marked with a pen as the ‘motor hot of trains that could be completed until the coil spot’. For threshold measurements, the coil was tangentially temperature reached 40 8C (i.e. before overheating of placed over the motor hot spot with the handle of the coil the coil occurred) was taken as a measure to characterize pointing backwards. the heating behaviour of each coil. Using the maximum Threshold intensities, expressed as a percentage of number of trains as dependent variable, we computed a maximum stimulator output, were approached from slightly two-factorial analysis of variance (ANOVA) with the suprathreshold intensities by reducing the stimulus intensity factors ‘coil’ (3 levels: test coil, Magstim coil and in 1% steps. Resting MT was defined as the minimum output Medtronic coil) and ‘intensity of stimulator output’ of the stimulator that induced a reliable MEP (about 50 mV in (3 levels: 40, 50, and 60% of maximum stimulator amplitude) in at least 5 of 10 consecutive trials when the FDI output) to assess differences in the heating of the coils. A muscle was completely relaxed. Complete relaxation was P value of !0.05 was considered significant. monitored using the audio feedback of EMG activity
    • T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 1481 (loudspeakers). Active MT was defined as the lowest intensity) multiplied by the repetition rate frep: stimulus intensity which induced a MEP of about 200 mV in amplitude in the tonically contracting FDI muscle in 5 of Pv Z Ev frep (4) 10 trials. Participants performed a tonic abduction of the right The heat dissipation PDiss could, therefore, be expressed index finger at 10% maximum force level. Continuous as the difference of the pulse power losses (Pv) and the heat auditory feedback of EMG activity in the FDI muscle was absorbed by the coil: provided to ensure a constant level of tonic contraction.   MEP’s were recorded using pairs of 5 mm Ag–AgCl dTCoil PDiss Z Pv K CCoil (5) surface electrodes taped to the belly and tendon of the right dt FDI muscle. EMG signal was amplified (50 mV/V, Toennies CCoil denotes the thermal capacitance. PDiss could also be ¨ Myograph II, Jaeger-Toennies, Wurzburg, Germany) and described by the temperature difference and the thermal bandpass filtered (20 Hz–10 kHz), digitized (sampling rate conductance of the coil (WCoil): 5 kHz, 400 ms sweeps, CED 1401 Laboratory Interface, Cambridge Electronic Design, Cambridge, UK), and stored PDiss Z ðTCoil K TE ÞWCoil (6) on a personal computer. TCoil, TE and PDiss are the coil temperature, the environ- Using the MT as dependent variable, a 3-factorial mental temperature and the energy dissipation, respectively. repeated-measures ANOVA was performed with within- The solution of the differential equation for the coil’s subject factors ‘coil’, ‘motor state’ and ‘stimulus orien- heating behaviour resulted in the time response of the tation’. The Greenhouse–Geisser method was used to temperature T(t): correct for non-sphericity. Conditional on a significant F   value, post-hoc paired-samples t tests were performed to dT describe the strength of main effects and the patterns of Pv K CCoil Coil Z PDiss Z ðTCoil K TE ÞWCoil dt interaction. A P value of !0.05 was considered significant. All data are given as meanGSD. P  t$W K Coil  0 TCoil ðtÞ Z v 1 K e CCoil C TE (7) WCoil 2.5. Computational simulations of the heating behaviour At baseline (time tZ0) the core of the coil should have the same temperature as the environment. This function is A thermal one-mass model was used to provide a valid based on the one-mass model and, therefore, is only reliable analytic framework of the relationship between the operat- when disregarding the after-heating of the Magstim coil ing conditions (i.e. the stimulation frequency and intensity) (two-mass model). The parameters WCoil, CCoil, PDiss can be and the heating-up behaviour of the coils. The one-mass extracted by comparing the measured time response of the model took into account the thermal conductivity and the temperature (Section 2.3) with the simulated function by heat emission to the environment, which is determined by means of curve-fitting. the thermal capacity. Thermal measurements (see Section Because of the small damping of the power circuit, a full 2.3) showed that a one-mass model was sufficient to oscillation of a sine function provided a good approximation describe the heating curves of all 3 coils during the of the current pulse configuration of a single biphasic administration of rTMS. In contrast to the test coil and the stimulus. Thus, the heat deposited in the coil per current Medtronic coil, the Magstim coil showed a delayed rise in pulse (Ev) could be described as a function of the occurring temperature after the cessation of rTMS. Therefore, a two- ^ peak current I, the pulse duration T and internal resistance mass model would be required to appropriately simulate the Ricoil of the coil: heating characteristics of the Magstim coil after the end of ðT ðT ^2 1 ^2 rTMS. Since the focus of the present study was on the Ev Z Ricoil I 2 ðtÞdt Z Ricoil I sinðutÞdt Z I Ricoil T heating of the coils during rTMS (and not after the end of 0 0 2 rTMS), we used the one-mass model which was appropriate rffiffiffiffi 1 ^2 1 ^ 2 ^ C^ to describe the heating behaviour of all investigated coils and LI Z CU 0 I Z U 2 2 L during a stimulation session. pffiffiffiffiffiffiffiffiffi The one-mass model was based on the simplification that and T Z 2p L$C the thermal conductance WCoil is not temperature-depen- (8) dent. This assumption represents a good approximation for the relatively small range of changes in temperature (from where L refers to the inductance of the coil, C to the 20 to 40 8C). A constant thermal conductance implies that ˆ capacitance and U to the discharge voltage of the stimulator. the heat emission is proportional to the temperature The heat deposited in the coil was thus directly difference. proportional to its internal resistance and increased squarely The applied pulse power losses Pv could be defined by with the peak current or the discharge voltage (always the pulse energy loss Ev (which depends on the stimulation expressed as percentage of the maximum value on
    • 1482 T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 the stimulators). Therefore, the maximal number of stimuli For the test coil, the slope of the heating curve was is an inverse square function of the stimulus intensity. flattened indicating a marked delay in the heating-up Table 1 lists the most important parameters used for process during the rTMS session (Fig. 2). Using the test thermal simulations. The 3 coils had approximately the coil, it was possible to give more than twice the number same DC resistance (Table 1). The test coil showed only a of stimuli in a single session compared with the two minimal increase in AC resistance at the frequency of the standard coils. This difference was also reflected in current produced by the stimulator (i.e. at 2.5–3 kHz). ANOVA as a main effect of the factor ‘type of coil’ Compared with the test coil, the ratios between the AC and (F (2;18)Z315,0; P!0.001). Post-hoc comparisons DC resistance were greater for the Magstim coil and the ´ (Scheffe test) confirmed that more rTMS trains could Medtronic coil (Table 1). be applied with the test coil than with the Magstim or Medtronic coil (P!0.001). There was also a difference in the maximum number of rTMS trains between both 3. Results standard coils. Overheating occurred earlier when the Magstim coil was used (PZ0.045; Fig. 2). The 3.1. Experiment 1: thermal measurements differences among coils were more pronounced at lower intensities of stimulations. This was reflected by an Fig. 2 plots the coil temperature against the number of interaction between ‘intensity’ and ‘type of coil’ trains (50 stimuli per train). At a given stimulus intensity, (F(4;18)Z22,5; P!0.001). the slopes of the heating curves of the same coil were nearly Measurements of coil temperature after the end of the identical regardless of the frequency of rTMS. In contrast, rTMS sessions revealed no further increase in coil the slopes of the heating curves increased with the intensity temperature for the test coil and Medtronic coil. In of rTMS. Thus, a smaller number of trains could be given contrast, the temperature of the Magstim coil continued to when the stimulus intensity was increased. Accordingly, rise after the end of rTMS; this effect was more ANOVA revealed a highly significant main effect of the pronounced at higher frequencies and intensities of factor ‘intensity’ (F(2;18)Z184,0; P!0.001). stimulation. Fig. 2. Each panel illustrates the heating curves of the three figure-of-eight shaped coils during rTMS using different combinations of intensities (40, 50, or 60% of maximum stimulator output) and frequencies (5, 10, or 20 Hz) of stimulation. The number of rTMS trains (abcissa) is plotted against the coil temperature (ordinate) as measured with the sensors in each coil. Each train consisted of 50 pulses. Stimulation was stopped as soon as coil temperature had reached 40 8C.
    • T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 1483 Fig. 3. Measurements of motor thresholds (MT) at rest (left panel) and during isometric contraction (right panel) in eleven healthy volunteers. MTs were determined with 3 different figure-of-eight shaped coils. Magnetic stimuli had a biphasic configuration and the initial phase in the coil had an anterior-to- posterior (a-p) orientation or a posterior-to-anterior (p-a) current orientation. Data correspond to the MTs of the right first dorsal interosseus muscle expressed as meansGSD. Asterisks denote a significant difference in MT between two conditions. 3.2. Experiment 2: threshold measurements For thermal estimations we used the analytic equation (see Section 2.5): Fig. 3 summarizes the group data for MT measurements. MTs were consistently lower during tonic contraction (main Pv  t$W K Coil  TCoil ðtÞ Z 1 K e CCoil C TE (9) effect of ‘motor state’: F(1;10)Z56,78; P!0.001) or when WCoil a-p orientation was used (main effect of ‘stimulus direction’: F(1;10)Z80,45; P!0.001). ANOVA for repeated measure- where the ratio CCoil/WCoil is the thermal time constant of ments revealed a main effect for the type of coil (F(1,9;18,8)Z the coil. Pv can be determined by Eqs. (4) and (8) and the 37,19; P!0.001). Post-hoc comparisons of corresponding measurement of Ricoil. The only unknowns are the thermal MT measurements disclosed that MTs measured with the capacitance CCoil and the thermal conductance WCoil of the test coil or the Medtronic coil were lower than MTs assessed coils. These coil parameters were determined by fitting the with the Magstim coil (P!0.001). No significant differ- heating curves (Fig. 4) and cooling curves (not displayed). ences were found between MTs measured with the test coil Based on these parameters, the time it takes for the coil and Medtronic coil. temperature to rise from ambient temperature to the cutoff There was also an interaction between the factors ‘state’ temperature of 40 8C (referred to as tmax) could be and ‘type of coil’ (F(2;20)Z3,70; PZ0.043), the factors ‘state’ and ‘stimulus direction’ (F(1;10)Z9,22; PZ0.01), as well as among all 3 factors (F(1,9;18,8)Z11,72; PZ0.001). These interactions demonstrate that the modulatory effect of the motor state (rest versus contraction) on MT depended on the type of coil and stimulus direction selected for rTMS. 3.3. Computational simulations of heating behaviour A thermal one-mass model was created to provide a valid analytic framework of the correlation between the operating conditions (i.e. the stimulation frequency and intensity) and the heating behaviour of the coils. Thermal measurements Fig. 4. Simulation of changes in coil temperature during rTMS. Simulations (see Section 3.2) showed that a one-mass model was were based on an initial coil temperature of 20 8C and a maximum sufficient to describe the test coil and the Medtronic coil temperature of 40 8C. Each curve indicates the maximum number of stimuli accurately. By contrast, the Magstim coil showed a notice- (ordinate) that can be applied with the test, Magstim and Medtronic coil at a able rise in temperature after the cessation of rTMS. In this given stimulus intensity (abcissa). The intensity of rTMS is expressed as % instance, the one-mass model was only appropriate to of the maximum MagPro stimulator output. The simulations were performed for continuous rTMS given at a rate of 5 Hz. The results of characterize the heating behaviour during the administration the simulations are valid for the entire range of frequencies that are of rTMS, but a two-mass model would be necessary to currently used for continuous rTMS (1–50 Hz) if the intensity of describe the heating characteristics after the end of rTMS. stimulation exceeds 20% of the maximal stimulator output.
    • 1484 T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 calculated: rTMS at rates of 5 Hz or more, especially when prolonged ! periods of rTMS are given during a relatively short period. CCoil 1 Previous attempts to delay overheating during rTMS tmax Z ln DT$WCoil ; DT Z ð40 8C K TE Þ WCoil 1 K Pv employed external cooling to increase convection of the (10) coil. However, cooling does not provide a straightforward solution to the problem. The commercially available air Using the function which describes tmax, we were able cooling system (Magstim Company; Whitland, Dyfed, UK) to calculate nmax. nmax refers to the maximal number is noisy and bulky rendering the coil more difficult to handle. of stimuli for each coil that can be applied at a given Water cooling was integrated into the first commercially stimulus intensity. available repetitive magnetic stimulator (Cadwell Labora- ! CCoil 1 tories, Inc., Kennewick, WA), but this approach requires nmax ¼ frep tmax ¼ ln (11) technical precautions to ensure the safety of rTMS. WCoil 1 K DT$WCoil Pv The comparison of heating curves revealed a marked Fig. 4 plots the calculated functions for each coil. reduction in the rise of temperature when the test coil with Compared with the two standard coils, the test coil showed a an optimized conductor geometry was used. When rTMS markedly improved heating behaviour. In addition, the was delivered through the test coil, the maximum number of Medtronic coil performed better that the Magstim coil. stimuli that could be given during a single session increased Though these differences among coils could be demon- at least by the factor of two. For instance, more than 1000 strated across the entire intensity range, absolute differences stimuli per session could be given at an intensity of 60% of in the maximum number of stimuli were most pronounced at maximum stimulator output before overheating occurred. low intensities of stimulation (i.e. below 40% of maximum We also found a consistent difference in the thermal stimulator output). properties between the two standard coils. The Magstim coil showed a faster rise in temperature than the Medtronic coil, especially at lower intensities of stimulation. According to our expectations, the heating up process 4. Discussion depended on the stimulation strength, which is directly proportional to the discharge voltage. The differences in the The main finding of this study is that the heating maximum number of stimuli per session were particularly behaviour of the stimulating coil can be reduced without evident at a relatively low stimulus intensity (40% of affecting the efficacy of rTMS. We also present an analytic maximum stimulator output). This can be attributed to a equation, which enables a reliable prediction of the stronger effect of convection at lower intensities of maximum number of magnetic stimuli that can be applied stimulation. At higher intensities (O50% of maximum with a distinct coil at a given intensity during a rTMS stimulator output) the cooling effect due to convection is no session. We discuss the implications of these results for the longer relevant to the heating of the coil, and the heating is current use of rTMS. now exclusively influenced by power losses and the heat capacitance. 4.1. Differences in heating behaviour The frequency of rTMS did not affect the heating of the coil because each rTMS protocol used the same number of We tested the heating behaviour during 9 different stimuli per train and an identical inter-train interval of 20 s. protocols of high-frequency rTMS. Intensities and frequen- Hence, the mean number of stimuli per minute and the cies of rTMS were selected to represent a range of rTMS cooling effect caused by convection were identical for each settings that are commonly used in high-frequency rTMS rTMS protocol. This is different for rTMS protocols using studies. Longer periods of high-frequency rTMS are usually continuous trains of rTMS. In this instance, the maximum applied at stimulus intensities around or below resting MT number of stimuli that can be applied during a single session in order to avoid the induction of seizures (Wassermann, is influenced by the repetition rate. 1998; Wassermann and Lisanby, 2001). In the present study, The temperature in the Magstim coil continued to rise for the stimulus intensities ranged from 40 to 60% of maximum several minutes after the end of rTMS. This can be stimulator output. These intensities covered the normal attributed to the housing material, which shows poor heat range of resting MTs in healthy subjects. Hence, it can be dissipation from the heated conductors to the environment concluded that intermediate intensities of 40–60% of and a high thermal capacitance. This resulted in a delayed maximum stimulator output matched the range of intensities increase in coil temperature as measured by the temperature that are usually chosen for high-frequency rTMS in clinical sensor which was located close to the surface of the coil. trials and research studies. We performed computational simulations to estimate the As outlined in the introduction, overheating of the coil still heating behaviour of each coil at a given stimulus intensity. constitutes a problem during the administration of rTMS. Since these estimations can be applied to every stimulating This problem is of great significance for high-frequency coil, this analytic correlation can be used for future thermal
    • T. Weyh et al. / Clinical Neurophysiology 116 (2005) 1477–1486 1485 estimations. A practical application of such thermal the Magstim rapid applied rTMS at a higher intensity estimations is to provide operational parameters for a relative to rTMS studies using a Medtronic stimulator. The given stimulating coil. The estimations extended our orientation of the stimulus also determines the biological thermal measurements which only covered intermediate effects of rTMS in the M1. Epidural recordings demon- intensities of stimulations (40–60% of maximum stimulator strated that, for monophasic TMS of the M1, a reversal of output). Simulations revealed that the use of the test coil the current direction from p-a direction to a-p direction allows a marked increase in the maximum number of stimuli caused a preferential activation of different sets of cortical per rTMS session across the entire intensity range. In neurons (Di Lazzaro et al., 2001). These differences need to concordance with our measurements, the absolute increase be born in mind when comparing rTMS studies of the M1 in the number of stimuli per session was most pronounced at that used different current directions. low intensities of stimulation (!40% of maximum In conclusion, the problem of overheating can be stimulator output). effectively tackled by improving the thermal properties of the coil used for rTMS. A marked delay in overheating can 4.2. Differences in motor threshold be achieved by optimizing the coil design without affecting the efficacy of stimulation. This allows the implementation MT at rest and during tonic contraction was determined of standard protocols of high-frequency rTMS without the to assess the effectiveness of transcranial cortex stimulation necessity to exchange the coil during the rTMS session or in healthy volunteers. We found significant differences in apply external cooling. MTs depending on the type of coil used for TMS. These differences in efficacy among coils were not caused by different properties of the magnetic stimulator because each coil was connected to the same energy source. MT Acknowledgements measurements revealed that MTs were highest when the Magstim coil was used for TMS. MTs were comparable H.R. Siebner and T.H. Weyh were supported by the when TMS was given through the Medtronic coil and test Volkswagen foundation (grant I/79 932). coil. These results demonstrate that the improved heating behaviour of the test coil did not reduce the efficacy of cortex stimulation. References Additionally, measurements of MT revealed that the orientation of the biphasic stimulus had a strong effect on Barker AT. The history and basic principles of magnetic nerve stimulation. the efficacy of rTMS both at rest and during tonic Electroencephalogr Clin Neurophysiol Suppl 1999;51:3–21. contraction. When the initial rising phase had an a-p Barker AT, Jalinous R, Freeston IL. 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