Clinical Neurophysiology 125 (2014) 1077–1078
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
Promise and perspective in transcranial magnetic stimulation See Article, pages 1202–1212
Since the introduction of transcranial magnetic stimulation (TMS), repeated efforts have been directed towards improving its focality and especially its penetration to deep brain regions. What a wonderful scope of applications deep focal TMS would open up! Ideas for achieving it have ranged from folding the ubiquitous figure-8 coil to form a double cone (Lontis et al., 2006), to triggering multiple adjacent coils synchronously or asynchronously (Ruohonen and Ilmoniemi, 1998; Huang et al., 2009), to creative variations on coil shape (Kraus et al., 1993; Ren et al., 1995; Hsu and Durand, 2001) and even to using MRI coils (Rohan et al., 2004). Most of the results have been disappointing. The modestly improved focusing obtainable with multiple adjacent coils comes at the cost of greatly diminished efficiency, while firing them at different times is defeated by leaky neuronal membranes (Deng et al., 2008). Indeed, theoretical analysis suggests that it is impossible by any means to produce a stronger field at depth than at the brain surface (Heller and van Hulsteyn, 1992). Perhaps the most promising innovation in recent years has been the h-coil, which cleverly directs coil return currents away from the scalp surface, so that the fields induced by the coil turns on the scalp are reinforced rather than nullified (Roth et al., 2002). However, a series of publications from Deng and colleagues has progressively narrowed the possibilities for TMS at depth. In a recent theoretical analysis of all 50 single-coil designs that had been published to that point, they described an inexorable tradeoff between stimulus focality and penetration depth (Deng et al., 2013). Now, in this issue of Clinical Neurophysiology, they extend that analysis using more a limited set of coils, including two additional designs that had been proposed but not widely implemented (Deng et al., 2014). With increasing penetration, the depth–focality–safety tradeoffs of different configurations begin to converge ominously. Effective TMS of targets at depths of 4 cm or more results in much stronger and more widespread superficial stimulation, which exceeds the limits of present rTMS safety guidelines over broad areas of cortex. In aiming deeper than 4 cm, the volume of stimulation becomes a substantial fraction of the entire brain. These conclusions represent a refinement of principles already understood by many experienced TMS researchers. Often the literature on ‘‘deep TMS’’ has depicted its spatial distribution accurately (Levkovitz et al., 2011). Occasionally, however, overenthusiasm has produced potentially misleading descriptions, such as ‘‘each generated field radially converges into a common point inside the brain’’ (Bersani et al., 2013) ‘‘the H1-coil enables
effective activation... up to depth of 7–8 cm’’ (Roth et al., 2007), ‘‘rTMS was delivered to the anterior cingulate cortex’’ (Kranz et al., 2010), and ‘‘medial prefrontal cortex deep transcranial magnetic stimulation’’ (Isserles et al., 2013). TMS will be most credible, safe, and successful when its users understand both the capabilities and limitations of the technologies they apply. Disclosure Dr. Epstein is the principal investigator for a recent TMS study sponsored by GlaxoSmithKline, investigator on three recent or current TMS studies sponsored by the National Institutes of Health, and investigator on one TMS study sponsored by the US Veterans Administration. He receives royalties from Neuronetics, Incorporated, which manufactures transcranial magnetic stimulators. One of the NIH studies noted above used Neuronetics equipment by permission of the Conflict of Interest Committee of Emory University. References Bersani FS, Minichino A, Enticott PG, Mazzarini L, Khan N, Antonacci G, et al. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry 2013;28:30–9. 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, Peterchev AV, Lisanby SH. Coil design considerations for deep-brain transcranial magnetic stimulation (dTMS). Conf Proc IEEE Eng Med Biol Soc 2008:5675–9. Deng Z-D, Lisanby SH, Peterchev AV. Coil design considerations for deep transcranial magnetic stimulation. Clin Neurophysiol 2014; 125:1202–12. Heller L, van Hulsteyn DB. Brain stimulation using electromagnetic sources: theoretical aspects. Biophys J 1992;63:129–38. Hsu KH, Durand DM. A 3-D differential coil design for localized magnetic stimulation. IEEE Trans Biomed Eng 2001;48:1162–8. Huang YZ, Sommer M, Thickbroom G, Hamada M, Pascual-Leonne A, Paulus W, et al. Consensus: new methodologies for brain stimulation. Brain stimul 2009;2:2–13. Isserles M, Shalev AY, Roth Y, Peri T, Kutz I, Zlotnick E, et al. Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder. A pilot study.. Brain Stimul 2013;6:377–83. Kranz G, Shamim EA, Lin PT, Kranz GS, Hallett M. Transcranial magnetic brain stimulation modulates blepharospasm: a randomized controlled study. Neurol 2010;75:1465–71. Kraus KH, Gugino LD, Levy WJ, Cadwell J, Roth BJ. The use of a cap-shaped coil for transcranial magnetic stimulation of the motor cortex. J Clin Neurophysiol 1993;10:353–62. Levkovitz Y, Rabany L, Harel EV, Zangen A. Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. Int J Neuropsychopharmacol 2011;12:991–6.
1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.12.097
1078
Editorial / Clinical Neurophysiology 125 (2014) 1077–1078
Lontis ER, Voigt M, Struijk JJ. Focality assessment in transcranial magnetic stimulation with double and cone coils. J Clin Neurophysiol 2006;23:463–72. Ren C, Tarjan PP, Popovic DB. A novel electric design for electromagnetic stimulation—the slinky coil. IEEE Trans Biomed Eng 1995;42:918–25. Rohan M, Parow A, Stoll AL, Demopulos C, Friedman S, Dager S, et al. Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator. Am J Psychiatry 2004;161:93–8. 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, Zangen A, Hallett M. A coil design for transcranial magnetic stimulation of deep brain regions. J Clin Neurophysiol 2002;19:361–70. Ruohonen J, Ilmoniemi RJ. Focusing and targeting of magnetic brain stimulation using multiple coils. Med Biol Eng Comput 1998;36:297–301.
⇑
Charles M. Epstein Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, United States ⇑ Tel.: +1 404 778 3633; fax: +1 404 778 4216. E-mail address: [email protected] Available online 21 December 2013
Contents lists available at ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
Editorial
Promise and perspective in transcranial magnetic stimulation See Article, pages 1202–1212
Since the introduction of transcranial magnetic stimulation (TMS), repeated efforts have been directed towards improving its focality and especially its penetration to deep brain regions. What a wonderful scope of applications deep focal TMS would open up! Ideas for achieving it have ranged from folding the ubiquitous figure-8 coil to form a double cone (Lontis et al., 2006), to triggering multiple adjacent coils synchronously or asynchronously (Ruohonen and Ilmoniemi, 1998; Huang et al., 2009), to creative variations on coil shape (Kraus et al., 1993; Ren et al., 1995; Hsu and Durand, 2001) and even to using MRI coils (Rohan et al., 2004). Most of the results have been disappointing. The modestly improved focusing obtainable with multiple adjacent coils comes at the cost of greatly diminished efficiency, while firing them at different times is defeated by leaky neuronal membranes (Deng et al., 2008). Indeed, theoretical analysis suggests that it is impossible by any means to produce a stronger field at depth than at the brain surface (Heller and van Hulsteyn, 1992). Perhaps the most promising innovation in recent years has been the h-coil, which cleverly directs coil return currents away from the scalp surface, so that the fields induced by the coil turns on the scalp are reinforced rather than nullified (Roth et al., 2002). However, a series of publications from Deng and colleagues has progressively narrowed the possibilities for TMS at depth. In a recent theoretical analysis of all 50 single-coil designs that had been published to that point, they described an inexorable tradeoff between stimulus focality and penetration depth (Deng et al., 2013). Now, in this issue of Clinical Neurophysiology, they extend that analysis using more a limited set of coils, including two additional designs that had been proposed but not widely implemented (Deng et al., 2014). With increasing penetration, the depth–focality–safety tradeoffs of different configurations begin to converge ominously. Effective TMS of targets at depths of 4 cm or more results in much stronger and more widespread superficial stimulation, which exceeds the limits of present rTMS safety guidelines over broad areas of cortex. In aiming deeper than 4 cm, the volume of stimulation becomes a substantial fraction of the entire brain. These conclusions represent a refinement of principles already understood by many experienced TMS researchers. Often the literature on ‘‘deep TMS’’ has depicted its spatial distribution accurately (Levkovitz et al., 2011). Occasionally, however, overenthusiasm has produced potentially misleading descriptions, such as ‘‘each generated field radially converges into a common point inside the brain’’ (Bersani et al., 2013) ‘‘the H1-coil enables
effective activation... up to depth of 7–8 cm’’ (Roth et al., 2007), ‘‘rTMS was delivered to the anterior cingulate cortex’’ (Kranz et al., 2010), and ‘‘medial prefrontal cortex deep transcranial magnetic stimulation’’ (Isserles et al., 2013). TMS will be most credible, safe, and successful when its users understand both the capabilities and limitations of the technologies they apply. Disclosure Dr. Epstein is the principal investigator for a recent TMS study sponsored by GlaxoSmithKline, investigator on three recent or current TMS studies sponsored by the National Institutes of Health, and investigator on one TMS study sponsored by the US Veterans Administration. He receives royalties from Neuronetics, Incorporated, which manufactures transcranial magnetic stimulators. One of the NIH studies noted above used Neuronetics equipment by permission of the Conflict of Interest Committee of Emory University. References Bersani FS, Minichino A, Enticott PG, Mazzarini L, Khan N, Antonacci G, et al. Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review. Eur Psychiatry 2013;28:30–9. 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, Peterchev AV, Lisanby SH. Coil design considerations for deep-brain transcranial magnetic stimulation (dTMS). Conf Proc IEEE Eng Med Biol Soc 2008:5675–9. Deng Z-D, Lisanby SH, Peterchev AV. Coil design considerations for deep transcranial magnetic stimulation. Clin Neurophysiol 2014; 125:1202–12. Heller L, van Hulsteyn DB. Brain stimulation using electromagnetic sources: theoretical aspects. Biophys J 1992;63:129–38. Hsu KH, Durand DM. A 3-D differential coil design for localized magnetic stimulation. IEEE Trans Biomed Eng 2001;48:1162–8. Huang YZ, Sommer M, Thickbroom G, Hamada M, Pascual-Leonne A, Paulus W, et al. Consensus: new methodologies for brain stimulation. Brain stimul 2009;2:2–13. Isserles M, Shalev AY, Roth Y, Peri T, Kutz I, Zlotnick E, et al. Effectiveness of deep transcranial magnetic stimulation combined with a brief exposure procedure in post-traumatic stress disorder. A pilot study.. Brain Stimul 2013;6:377–83. Kranz G, Shamim EA, Lin PT, Kranz GS, Hallett M. Transcranial magnetic brain stimulation modulates blepharospasm: a randomized controlled study. Neurol 2010;75:1465–71. Kraus KH, Gugino LD, Levy WJ, Cadwell J, Roth BJ. The use of a cap-shaped coil for transcranial magnetic stimulation of the motor cortex. J Clin Neurophysiol 1993;10:353–62. Levkovitz Y, Rabany L, Harel EV, Zangen A. Deep transcranial magnetic stimulation add-on for treatment of negative symptoms and cognitive deficits of schizophrenia: a feasibility study. Int J Neuropsychopharmacol 2011;12:991–6.
1388-2457/$36.00 Ó 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2013.12.097
1078
Editorial / Clinical Neurophysiology 125 (2014) 1077–1078
Lontis ER, Voigt M, Struijk JJ. Focality assessment in transcranial magnetic stimulation with double and cone coils. J Clin Neurophysiol 2006;23:463–72. Ren C, Tarjan PP, Popovic DB. A novel electric design for electromagnetic stimulation—the slinky coil. IEEE Trans Biomed Eng 1995;42:918–25. Rohan M, Parow A, Stoll AL, Demopulos C, Friedman S, Dager S, et al. Low-field magnetic stimulation in bipolar depression using an MRI-based stimulator. Am J Psychiatry 2004;161:93–8. 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, Zangen A, Hallett M. A coil design for transcranial magnetic stimulation of deep brain regions. J Clin Neurophysiol 2002;19:361–70. Ruohonen J, Ilmoniemi RJ. Focusing and targeting of magnetic brain stimulation using multiple coils. Med Biol Eng Comput 1998;36:297–301.
⇑
Charles M. Epstein Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, United States ⇑ Tel.: +1 404 778 3633; fax: +1 404 778 4216. E-mail address: [email protected] Available online 21 December 2013
