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Letters to the Editor / Clinical Neurophysiology 126 (2015) 1453–1457
Fig. 1. Performance metrics of the Magstim figure-8 coil (red diamonds), the Magstim double cone coil (green triangles), the Magstim 90 mm circular coil (orange squares) and the Brainsway H1 coil (blue circles) for stimulation target depths of 2–6 cm: (a) ratio between maximum electric field at the surface and the deeper region field at threshold for neural activation, E2cm/Eth; (b) directly activated brain volume, VA, as % of total brain volume. Filled symbols represent results of spherical head model simulations (Deng et al., 2014) and open symbols represent results of phantom brain field measurements. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
treatment. It should be noted that additional factors apart from field intensity may affect the neuronal response, such as neural structures orientation relative to the field direction. Regarding the relative importance of different factors with respect to safety issues, it should be noted that over the more than 5000 subjects who have undergone deep TMS sessions with H-coils (including clinical studies and commercial treatments), the total number of reported seizures is 6. In all of these 6 cases, additional risk factors were present (such as history of epileptic seizures, high doses of medications that lower the seizure threshold or alcohol consumption). Therefore, overall rate of seizures in deep TMS sessions seems to be low. As noted by the authors (Deng et al., 2014), the maximal induced field in the brain is similar between H-coils and standard TMS coils. The depth and volume of stimulation is different indeed, but the maximal intensity is similar. Hence the bulk of clinical data seems to indicate that it is the maximal field induced in the brain, rather than the overall stimulated volume, which is the crucial factor that contributes to the risk of seizure.
Disclosure Dr. Roth and Prof. Zangen are inventors of deep TMS coils and have financial interests in Brainsway Inc. Dr. Pell is an employee of Brainsway Inc.
References Dalla Libera D, Colombo B, Coppi E, Straffi L, Chieffo R, Spagnolo F, et al. Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied with H-coil for chronic migraine prophylaxis. Clin Neurophysiol 2011;122:S145–6. Deng Z-D, Lisanby SH, Peterchev AV. Coil design considerations for deep transcranial magnetic stimulation. Clin Neurophysiol 2014;125:1202–12. Kranz G, Shamim EA, Lin PT, Kranz GS, Hallett M. Transcranial magnetic brain stimulation modulates blepharospasm: a randomized controlled study. Neurology 2010;75:1465–71. Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol 2007;24:31–8. Roth Y, Pell GS, Zangen A. Commentary on: Deng et al., Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul 2013;6:14–5. Roth Y, Pell GS, Chistyakov AV, Sinai A, Zangen A, Zaaroor M. Motor cortex activation by H-coil and figure-8 coil at different depths. Combined motor threshold and electric field distribution study. Clin Neurophysiol 2014;125:336–43. Zangen A, Roth Y, Hallett M. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol 2005;116:775–9.
Yiftach Roth Gaby S. Pell ⇑ Abraham Zangen Department of Life Sciences, Ben-Gurion University, Be’er Sheva, Israel ⇑ Corresponding author at: Department of Life Sciences, Ben-Gurion University of the Negev, POB 653, Be’er Sheva 84105, Israel. Tel.: +972 8 647 2646; fax: +972 8 646 1713. E-mail address: [email protected] (A. Zangen) Available online 28 October 2014 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2014.10.144
On the characterization of coils for deep transcranial magnetic stimulation
We welcome the opportunity to reply to Roth and colleagues’ comments on our article (Deng et al., 2014), which explore the fundamental limits of performing transcranial magnetic stimulation of deep brain structures. We agree with Roth et al. (2015) that the spherical model used in our work has limitations, which we have acknowledged both in this paper and in previous work, e.g. (Deng et al., 2011). Nevertheless, our computational spherical model is useful in delineating general trends and principles, and has advantages compared to the phantom measurement approach of Roth et al., including more than 10 times higher spatial resolution, as discussed below. In comparing the electric field simulation results from our spherical model with measurements in the homogenous, realistically shaped head phantom of Roth et al., the order of performance of coils ranked according to superficial cortex stimulation strength (E2cm/Eth) and activated brain volume (VA) versus depth is mostly preserved with some exceptions. Some of the discrepancies in coil performance could arise from differences in the size and/or shape of the spherical model and the phantom, as well as the limited resolution of the phantom measurements. The resolution of the field measurements in the phantom is limited to the size of the dipole probe (Tofts and Branston, 1991), which was reported to be 17 mm (Roth et al., 2007). In contrast, our computational model has a spatial resolution of approximately 1 mm (Deng et al., 2011). Differences in the definition and evaluation of coil performance metrics may also contribute. For instance, in
Letters to the Editor / Clinical Neurophysiology 126 (2015) 1453–1457
Fig. 1b of Roth et al. (2015), it appears that all coils have VA = 0 at depth of 2 cm, whereas in our calculation (Fig. 6 in Deng et al. (2014)) VA is non-zero and varies across the different coils at 2 cm depth. This implies that Roth et al. assumed that the cortical surface is at a depth of 2 cm, whereas in our model it is at 1.5 cm depth. A particularly unexpected result of the phantom measurements is that the H1 coil appears to be the most focal coil for stimulation depths up to 3 cm, while simultaneously retaining the lowest superficial electric field strength. This result is surprising since it is counterintuitive that the H1 coil—a relatively large coil without a well-defined focal point—would be more focal than the standard figure-8 coil that is established as a configuration with focality near the highest achievable (Deng et al., 2013; Koponen et al., 2014). Indeed, if replicable, this result would force a re-evaluation of the coil configurations used for focal superficial TMS. We suspect, however, that this result may be confounded by the limited measurement resolution. We agree with Roth et al. that TMS coils targeting specific deep brain regions must be designed considering the head anatomy. It should be noted, though, that their head phantom is a homogeneous tank of saline, and therefore it cannot accurately assess the electric field strength in specific brain structures, which depends on the heterogeneous and anisotropic conductivity of the brain tissues (Opitz et al., 2011; Thielscher et al., 2011). Therefore characterization of specific targets could be more accurate with a high resolution, anatomically realistic head model that properly accounts for the electrical properties of the various tissues, as recently done by Guadagnin et al. (2014). Notably, they reported that in their realistic head model, the H coils had smaller stimulation depth compared to large circular coils and double cone type coils (Guadagnin et al., 2014). Finally, based on the similar maximal electric field in the brain in clinical use of H coils and the more focal conventional figure-8 coils, and the relatively low incidence of seizures with H coils (6 seizures in about 5000 subjects, reported in their letter), Roth et al. concluded that the most important factor that contributes to the risk of seizure is the maximal field strength, and not the stimulated brain volume. This argument assumes equivalent seizure risk between H coils and standard figure-8 coils, which to our knowledge has not been assessed for matched stimulus train parameters. Indeed, the question of the relative contributions of the TMS electric field strength and focality to seizure induction remains largely unexplored with properly controlled studies. Acknowledgments This work was supported in part by NIH grants KL2 TR00111502, R01MH60884, R01MH091083, and R01NS088674. Conflict of interest: Dr. Deng is inventor on a patent and patent applications on TMS/MST technology assigned to Columbia and Duke. In the past 2 years Dr. Lisanby has served as Principal Investigator on industry-sponsored research grants to Duke (ANS/St. Jude Medical, NeoSync, Brainsway); equipment loans to Duke (Magstim, MagVenture); is co-inventor on a patent and patent applications on TMS technology; is supported by grants from NIH (R01MH091083-01, 5U01MH084241-02, 5R01MH06088409), Stanley Medical Research Institute, Brain and Behavior Research Foundation, and the Wallace H. Coulter Foundation; and has no consultancies, speakers bureau memberships, board affiliations, or equity holdings in related device industries.
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Dr. Peterchev is inventor on patents and patent applications on TMS/MST technology assigned to Columbia and Duke, including technology licensed to Rogue Research; was Principal Investigator on a research grant to Duke from Rogue Research and equipment loans to Columbia and Duke by Magstim and MagVenture; and has received patent royalties and travel support from Rogue Research through Columbia and Duke for TMS technology. References Deng Z-D, Lisanby SH, Peterchev AV. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study. J Neural Eng 2011;8:016007. Deng Z-D, Lisanby SH, Peterchev AV. Electric field depth–focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul 2013;6:1–13. Deng Z-D, Lisanby SH, Peterchev AV. Coil design considerations for deep transcranial magnetic stimulation. Clin Neurophysiol 2014;125:1202–12. Guadagnin V, Parazzini M, Liorni I, Fiocchi S, Ravazzani P. Modelling of deep transcranial magnetic stimulation: different coil configurations. Conf Proc IEEE Eng Med Biol Soc 2014:4306–9. Koponen LM, Nieminen JO, Ilmoniemi RJ. Minimum-energy coils for transcranial magnetic stimulation: application to focal stimulation. Brain Stimul 2014. http://dx.doi.org/10.1016/j.brs.2014.10.002 [E-Pub: Oct. 9, 2014]. Opitz A, Windhoff M, Heidemann RM, Turner R, Thielscher A. How the brain tissue shapes the electric field induced by transcranial magnetic stimulation. Neuroimage 2011;58:849–59. Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol 2007;24:31–8. Roth Y, Pell GS, Zangen A. Realistic shape head model and spherical model as methods for TMS coil characterization. Clin Neurophysiol 2015;126:1455–6. Thielscher A, Opitz A, Windhoff M. Impact of the gyral geometry on the electric field induced by transcranial magnetic stimulation. Neuroimage 2011;54: 234–43. Tofts PS, Branston NM. The measurement of electric field, and the influence of surface charge, in magnetic stimulation. Electroencephalogr Clin Neurophysiol 1991;81:238–9.
Zhi-De Deng Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA E-mail address: [email protected] Sarah H. Lisanby Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Department of Psychology and Neuroscience, Duke University, Durham, NC, USA E-mail address: [email protected]
⇑
Angel V. Peterchev Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Department of Biomedical Engineering, Duke University, Durham, NC, USA Department of Electrical and Computer Engineering, Duke University, Durham, NC, USA ⇑ Address: Department of Psychiatry and Behavioral Sciences, Duke University, Box 3620 DUMC, Durham, NC 27710, USA. Tel.: +1 919 684 0383; fax: +1 919 681 9962. E-mail address: [email protected] Available online 28 October 2014 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2014.10.144
Letters to the Editor / Clinical Neurophysiology 126 (2015) 1453–1457
Fig. 1. Performance metrics of the Magstim figure-8 coil (red diamonds), the Magstim double cone coil (green triangles), the Magstim 90 mm circular coil (orange squares) and the Brainsway H1 coil (blue circles) for stimulation target depths of 2–6 cm: (a) ratio between maximum electric field at the surface and the deeper region field at threshold for neural activation, E2cm/Eth; (b) directly activated brain volume, VA, as % of total brain volume. Filled symbols represent results of spherical head model simulations (Deng et al., 2014) and open symbols represent results of phantom brain field measurements. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
treatment. It should be noted that additional factors apart from field intensity may affect the neuronal response, such as neural structures orientation relative to the field direction. Regarding the relative importance of different factors with respect to safety issues, it should be noted that over the more than 5000 subjects who have undergone deep TMS sessions with H-coils (including clinical studies and commercial treatments), the total number of reported seizures is 6. In all of these 6 cases, additional risk factors were present (such as history of epileptic seizures, high doses of medications that lower the seizure threshold or alcohol consumption). Therefore, overall rate of seizures in deep TMS sessions seems to be low. As noted by the authors (Deng et al., 2014), the maximal induced field in the brain is similar between H-coils and standard TMS coils. The depth and volume of stimulation is different indeed, but the maximal intensity is similar. Hence the bulk of clinical data seems to indicate that it is the maximal field induced in the brain, rather than the overall stimulated volume, which is the crucial factor that contributes to the risk of seizure.
Disclosure Dr. Roth and Prof. Zangen are inventors of deep TMS coils and have financial interests in Brainsway Inc. Dr. Pell is an employee of Brainsway Inc.
References Dalla Libera D, Colombo B, Coppi E, Straffi L, Chieffo R, Spagnolo F, et al. Effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) applied with H-coil for chronic migraine prophylaxis. Clin Neurophysiol 2011;122:S145–6. Deng Z-D, Lisanby SH, Peterchev AV. Coil design considerations for deep transcranial magnetic stimulation. Clin Neurophysiol 2014;125:1202–12. Kranz G, Shamim EA, Lin PT, Kranz GS, Hallett M. Transcranial magnetic brain stimulation modulates blepharospasm: a randomized controlled study. Neurology 2010;75:1465–71. Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol 2007;24:31–8. Roth Y, Pell GS, Zangen A. Commentary on: Deng et al., Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul 2013;6:14–5. Roth Y, Pell GS, Chistyakov AV, Sinai A, Zangen A, Zaaroor M. Motor cortex activation by H-coil and figure-8 coil at different depths. Combined motor threshold and electric field distribution study. Clin Neurophysiol 2014;125:336–43. Zangen A, Roth Y, Hallett M. Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil. Clin Neurophysiol 2005;116:775–9.
Yiftach Roth Gaby S. Pell ⇑ Abraham Zangen Department of Life Sciences, Ben-Gurion University, Be’er Sheva, Israel ⇑ Corresponding author at: Department of Life Sciences, Ben-Gurion University of the Negev, POB 653, Be’er Sheva 84105, Israel. Tel.: +972 8 647 2646; fax: +972 8 646 1713. E-mail address: [email protected] (A. Zangen) Available online 28 October 2014 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2014.10.144
On the characterization of coils for deep transcranial magnetic stimulation
We welcome the opportunity to reply to Roth and colleagues’ comments on our article (Deng et al., 2014), which explore the fundamental limits of performing transcranial magnetic stimulation of deep brain structures. We agree with Roth et al. (2015) that the spherical model used in our work has limitations, which we have acknowledged both in this paper and in previous work, e.g. (Deng et al., 2011). Nevertheless, our computational spherical model is useful in delineating general trends and principles, and has advantages compared to the phantom measurement approach of Roth et al., including more than 10 times higher spatial resolution, as discussed below. In comparing the electric field simulation results from our spherical model with measurements in the homogenous, realistically shaped head phantom of Roth et al., the order of performance of coils ranked according to superficial cortex stimulation strength (E2cm/Eth) and activated brain volume (VA) versus depth is mostly preserved with some exceptions. Some of the discrepancies in coil performance could arise from differences in the size and/or shape of the spherical model and the phantom, as well as the limited resolution of the phantom measurements. The resolution of the field measurements in the phantom is limited to the size of the dipole probe (Tofts and Branston, 1991), which was reported to be 17 mm (Roth et al., 2007). In contrast, our computational model has a spatial resolution of approximately 1 mm (Deng et al., 2011). Differences in the definition and evaluation of coil performance metrics may also contribute. For instance, in
Letters to the Editor / Clinical Neurophysiology 126 (2015) 1453–1457
Fig. 1b of Roth et al. (2015), it appears that all coils have VA = 0 at depth of 2 cm, whereas in our calculation (Fig. 6 in Deng et al. (2014)) VA is non-zero and varies across the different coils at 2 cm depth. This implies that Roth et al. assumed that the cortical surface is at a depth of 2 cm, whereas in our model it is at 1.5 cm depth. A particularly unexpected result of the phantom measurements is that the H1 coil appears to be the most focal coil for stimulation depths up to 3 cm, while simultaneously retaining the lowest superficial electric field strength. This result is surprising since it is counterintuitive that the H1 coil—a relatively large coil without a well-defined focal point—would be more focal than the standard figure-8 coil that is established as a configuration with focality near the highest achievable (Deng et al., 2013; Koponen et al., 2014). Indeed, if replicable, this result would force a re-evaluation of the coil configurations used for focal superficial TMS. We suspect, however, that this result may be confounded by the limited measurement resolution. We agree with Roth et al. that TMS coils targeting specific deep brain regions must be designed considering the head anatomy. It should be noted, though, that their head phantom is a homogeneous tank of saline, and therefore it cannot accurately assess the electric field strength in specific brain structures, which depends on the heterogeneous and anisotropic conductivity of the brain tissues (Opitz et al., 2011; Thielscher et al., 2011). Therefore characterization of specific targets could be more accurate with a high resolution, anatomically realistic head model that properly accounts for the electrical properties of the various tissues, as recently done by Guadagnin et al. (2014). Notably, they reported that in their realistic head model, the H coils had smaller stimulation depth compared to large circular coils and double cone type coils (Guadagnin et al., 2014). Finally, based on the similar maximal electric field in the brain in clinical use of H coils and the more focal conventional figure-8 coils, and the relatively low incidence of seizures with H coils (6 seizures in about 5000 subjects, reported in their letter), Roth et al. concluded that the most important factor that contributes to the risk of seizure is the maximal field strength, and not the stimulated brain volume. This argument assumes equivalent seizure risk between H coils and standard figure-8 coils, which to our knowledge has not been assessed for matched stimulus train parameters. Indeed, the question of the relative contributions of the TMS electric field strength and focality to seizure induction remains largely unexplored with properly controlled studies. Acknowledgments This work was supported in part by NIH grants KL2 TR00111502, R01MH60884, R01MH091083, and R01NS088674. Conflict of interest: Dr. Deng is inventor on a patent and patent applications on TMS/MST technology assigned to Columbia and Duke. In the past 2 years Dr. Lisanby has served as Principal Investigator on industry-sponsored research grants to Duke (ANS/St. Jude Medical, NeoSync, Brainsway); equipment loans to Duke (Magstim, MagVenture); is co-inventor on a patent and patent applications on TMS technology; is supported by grants from NIH (R01MH091083-01, 5U01MH084241-02, 5R01MH06088409), Stanley Medical Research Institute, Brain and Behavior Research Foundation, and the Wallace H. Coulter Foundation; and has no consultancies, speakers bureau memberships, board affiliations, or equity holdings in related device industries.
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Dr. Peterchev is inventor on patents and patent applications on TMS/MST technology assigned to Columbia and Duke, including technology licensed to Rogue Research; was Principal Investigator on a research grant to Duke from Rogue Research and equipment loans to Columbia and Duke by Magstim and MagVenture; and has received patent royalties and travel support from Rogue Research through Columbia and Duke for TMS technology. References Deng Z-D, Lisanby SH, Peterchev AV. Electric field strength and focality in electroconvulsive therapy and magnetic seizure therapy: a finite element simulation study. J Neural Eng 2011;8:016007. Deng Z-D, Lisanby SH, Peterchev AV. Electric field depth–focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul 2013;6:1–13. Deng Z-D, Lisanby SH, Peterchev AV. Coil design considerations for deep transcranial magnetic stimulation. Clin Neurophysiol 2014;125:1202–12. Guadagnin V, Parazzini M, Liorni I, Fiocchi S, Ravazzani P. Modelling of deep transcranial magnetic stimulation: different coil configurations. Conf Proc IEEE Eng Med Biol Soc 2014:4306–9. Koponen LM, Nieminen JO, Ilmoniemi RJ. Minimum-energy coils for transcranial magnetic stimulation: application to focal stimulation. Brain Stimul 2014. http://dx.doi.org/10.1016/j.brs.2014.10.002 [E-Pub: Oct. 9, 2014]. Opitz A, Windhoff M, Heidemann RM, Turner R, Thielscher A. How the brain tissue shapes the electric field induced by transcranial magnetic stimulation. Neuroimage 2011;58:849–59. Roth Y, Amir A, Levkovitz Y, Zangen A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J Clin Neurophysiol 2007;24:31–8. Roth Y, Pell GS, Zangen A. Realistic shape head model and spherical model as methods for TMS coil characterization. Clin Neurophysiol 2015;126:1455–6. Thielscher A, Opitz A, Windhoff M. Impact of the gyral geometry on the electric field induced by transcranial magnetic stimulation. Neuroimage 2011;54: 234–43. Tofts PS, Branston NM. The measurement of electric field, and the influence of surface charge, in magnetic stimulation. Electroencephalogr Clin Neurophysiol 1991;81:238–9.
Zhi-De Deng Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA E-mail address: [email protected] Sarah H. Lisanby Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Department of Psychology and Neuroscience, Duke University, Durham, NC, USA E-mail address: [email protected]
⇑
Angel V. Peterchev Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Department of Biomedical Engineering, Duke University, Durham, NC, USA Department of Electrical and Computer Engineering, Duke University, Durham, NC, USA ⇑ Address: Department of Psychiatry and Behavioral Sciences, Duke University, Box 3620 DUMC, Durham, NC 27710, USA. Tel.: +1 919 684 0383; fax: +1 919 681 9962. E-mail address: [email protected] Available online 28 October 2014 1388-2457/Ó 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2014.10.144
