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However, its clinical efficacy is fundamentally limited due to the current shunting effect of the scalp and safety issues. A newer electrical stimulation technique called subcutaneous electrical stimulation (SES) promises to overcome the limitations of TES by applying currents directly at the site of the disorder through the skull. While SES seems promising, the electrophysiological effect of SES compared to TES is still unknown, thus limiting its broader application. Here we comprehensively analyze the SES and TES to demonstrate the effectiveness and advantages of SES. Beagles were bilaterally implanted with subdural strips for intracranial electroencephalography and electric field recording. For the intracerebral electric field prediction, we designed a 3D electromagnetic simulation framework and simulated TES and SES. In the beagle model, SES induces three to four-fold larger cerebral electric fields compared to TES, and significant changes in power ratio of brainwaves were observed only in SES. Our prediction framework suggests that the field penetration of SES would be several-fold larger than TES in human brains. These results demonstrate that the SES would significantly enhance the neuromodulatory effects compared to conventional TES and overcome the TES limitations.<\/jats:p>","DOI":"10.1038\/s41598-020-64378-6","type":"journal-article","created":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T10:03:55Z","timestamp":1588241035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Analyzing the advantages of subcutaneous over transcutaneous electrical stimulation for activating brainwaves"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8372-4140","authenticated-orcid":false,"given":"Wonok","family":"Kang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8092-3208","authenticated-orcid":false,"given":"Jiho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu Ri","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo Ram","family":"Chung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duk L.","family":"Na","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Min","family":"Shon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung-Min","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,4,30]]},"reference":[{"key":"64378_CR1","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1161\/STROKEAHA.109.576785","volume":"41","author":"JM Baker","year":"2010","unstructured":"Baker, J. M., Rorden, C. & Fridriksson, J. Using transcranial direct-current stimulation to treat stroke patients with aphasia. Stroke 41, 1229\u20131236, https:\/\/doi.org\/10.1161\/STROKEAHA.109.576785 (2010).","journal-title":"Stroke"},{"key":"64378_CR2","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1111\/j.1460-9568.2012.08035.x","volume":"35","author":"MM Shafi","year":"2012","unstructured":"Shafi, M. M., Westover, M. B., Fox, M. D. & Pascual-Leone, A. Exploration and modulation of brain network interactions with noninvasive brain stimulation in combination with neuroimaging. European Journal of Neuroscience 35, 805\u2013825, https:\/\/doi.org\/10.1111\/j.1460-9568.2012.08035.x (2012).","journal-title":"European Journal of Neuroscience"},{"key":"64378_CR3","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.brs.2013.01.009","volume":"6","author":"N Auvichayapat","year":"2013","unstructured":"Auvichayapat, N. et al. Transcranial direct current stimulation for treatment of refractory childhood focal epilepsy. Brain stimulation 6, 696\u2013700, https:\/\/doi.org\/10.1016\/j.brs.2013.01.009 (2013).","journal-title":"Brain stimulation"},{"key":"64378_CR4","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1109\/TNSRE.2012.2200046","volume":"21","author":"G Ruffini","year":"2013","unstructured":"Ruffini, G. et al. Transcranial current brain stimulation (tCS): models and technologies. IEEE Transactions on Neural Systems and Rehabilitation Engineering 21, 333\u2013345, https:\/\/doi.org\/10.1109\/TNSRE.2012.2200046 (2013).","journal-title":"IEEE Transactions on Neural Systems and Rehabilitation Engineering"},{"key":"64378_CR5","doi-asserted-by":"publisher","first-page":"159","DOI":"10.3389\/fnhum.2017.00159","volume":"11","author":"F Yavari","year":"2017","unstructured":"Yavari, F., Nitsche, M. A. & Ekhtiari, H. Transcranial electric stimulation for precision medicine: a spatiomechanistic framework. Frontiers in human neuroscience 11, 159, https:\/\/doi.org\/10.3389\/fnhum.2017.00159 (2017).","journal-title":"Frontiers in human neuroscience"},{"key":"64378_CR6","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1111\/j.1469-7793.2000.t01-1-00633.x","volume":"527","author":"MA Nitsche","year":"2000","unstructured":"Nitsche, M. A. & Paulus, W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of physiology 527, 633\u2013639, https:\/\/doi.org\/10.1111\/j.1469-7793.2000.t01-1-00633.x (2000).","journal-title":"The Journal of physiology"},{"key":"64378_CR7","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1212\/WNL.57.10.1899","volume":"57","author":"MA Nitsche","year":"2001","unstructured":"Nitsche, M. A. & Paulus, W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. 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