{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:49:28Z","timestamp":1791139768017,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AscenZion Neuromodulation Co. Pte. Ltd, Singapore"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Various brain stimulation devices capable of generating high-frequency currents are readily available. However, our comprehension of the potential side or therapeutic effects associated with high-frequency transcranial pulsed current stimulation (tPCS), particularly concerning the new 400 Hz tPCS device, AscenZ-IV Stimulator, developed by AscenZion Neuromodulation Co. Pte. Ltd. in Singapore, remains incomplete.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>This study examines preliminary parameters for the safe and comfortable application of 400 Hz tPCS at intensities below 2 mA.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In a cross-sectional study, 45 healthy participants underwent sub-2 mA 400 Hz tPCS to assess sensory, motor, and pain thresholds on the dominant side. Study 1 (N = 15) targeted the primary motor cortex of the right-hand area, while study 2 (N = 30) focused on the back of the right forearm.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Study one showed that increasing the current intensity gradually resulted in no responses at sub-0.3 mA levels, but higher intensities (p &lt; 0.001) induced sensory perception and pain responses. Study two replicated these findings and additionally induced motor responses along with the sensory and pain responses.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Despite the theoretical classification of tPCS as a subsensory level of stimulation, and the expectation that individuals receiving this type of current should not typically feel its application on the body, this high-frequency tPCS device generates different levels of stimulation due to the physiological phenomenon known as temporal summation. These novel levels of stimulation could be viewed as either potential \u201cside-effects\u201d of high frequency tPCS or as additional \u201ctherapeutic benefits\u201d. This dual capacity may position the device as one that generates both neuromodulatory and neurostimulatory currents. Comprehensive comprehension of this is vital for the development of therapeutic protocols that incorporate high-frequency tPCS.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0290137","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T18:27:27Z","timestamp":1702492047000},"page":"e0290137","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploring sensory, motor, and pain responses as potential side or therapeutic effects of sub-2 mA, 400 Hz transcranial pulsed current stimulation"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-4510","authenticated-orcid":true,"given":"Shapour","family":"Jaberzadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Zoghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"issue":"6","key":"pone.0290137.ref001","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1007\/s10545-018-0181-4","article-title":"Transcranial electrical stimulation (tES) mechanisms and its effects on cortical excitability and connectivity.","volume":"41","author":"T Reed","year":"2018","journal-title":"J Inherit Metab Dis"},{"issue":"3","key":"pone.0290137.ref002","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0003-9993(98)90006-5","article-title":"Sensory, motor, and pain thresholds for stimulation with medium frequency alternating current","volume":"79","author":"AR Ward","year":"1998","journal-title":"Arch Phys Med Rehabil"},{"issue":"3","key":"pone.0290137.ref003","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/BF00376776","article-title":"Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system","volume":"68","author":"L Arendt-Nielsen","year":"1994","journal-title":"Eur J Appl Physiol Occup Physiol"},{"issue":"2","key":"pone.0290137.ref004","first-page":"201","article-title":"Neuromuscular electrical stimulation for skeletal muscle function.","volume":"85","author":"BM Doucet","year":"2012","journal-title":"Yale J Biol Med"},{"issue":"1","key":"pone.0290137.ref005","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s12887-021-02615-1","article-title":"The effect of combined transcranial pulsed current stimulation and transcutaneous electrical nerve stimulation on lower limb spasticity in children with spastic cerebral palsy: a randomized and controlled clinical study","volume":"21","author":"Z Liu","year":"2021","journal-title":"BMC Pediatr"},{"issue":"1","key":"pone.0290137.ref006","doi-asserted-by":"crossref","first-page":"15758","DOI":"10.1038\/s41598-017-15966-6","article-title":"Dynamics of high frequency brain activity","volume":"7","author":"SX Moffett","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0290137.ref007","article-title":"Ultrafast (400 Hz) network oscillations induced in mouse barrel cortex by optogenetic activation of thalamocortical axons.","volume":"12","author":"H Hu","year":"2023","journal-title":"Elife"},{"issue":"1","key":"pone.0290137.ref008","doi-asserted-by":"crossref","first-page":"7695","DOI":"10.1038\/s41598-020-64717-7","article-title":"Detecting cortical circuits resonant to high-frequency oscillations in the human primary motor cortex: a TMS-tACS study.","volume":"10","author":"A Guerra","year":"2020","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0290137.ref009","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1113\/jphysiol.1926.sp002281","article-title":"The impulses produced by sensory nerve-endings: Part II. The response of a Single End-Organ","volume":"61","author":"ED Adrian","year":"1926","journal-title":"J Physiol"},{"issue":"4","key":"pone.0290137.ref010","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1080\/03093640601058162","article-title":"Balance control enhancement using sub-sensory stimulation and visual-auditory biofeedback strategies for amputee subjects","volume":"31","author":"MY Lee","year":"2007","journal-title":"Prosthet Orthot Int"},{"issue":"4","key":"pone.0290137.ref011","doi-asserted-by":"crossref","first-page":"208","DOI":"10.2519\/jospt.1996.24.4.208","article-title":"Transcutaneous electrical nerve stimulation for the control of pain in musculoskeletal disorders","volume":"24","author":"AJ Robinson","year":"1996","journal-title":"J Orthop Sports Phys Ther"},{"issue":"9","key":"pone.0290137.ref012","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1016\/j.apmr.2009.02.022","article-title":"Lowering of sensory, motor, and pain-tolerance thresholds with burst duration using kilohertz-frequency alternating current electric stimulation: part II.","volume":"90","author":"AR Ward","year":"2009","journal-title":"Arch Phys Med Rehabil"},{"issue":"8","key":"pone.0290137.ref013","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.apmr.2007.04.009","article-title":"Lowering of sensory, motor, and pain-tolerance thresholds with burst duration using kilohertz-frequency alternating current electric stimulation","volume":"88","author":"AR Ward","year":"2007","journal-title":"Arch Phys Med Rehabil"},{"issue":"3","key":"pone.0290137.ref014","first-page":"397","article-title":"Perception of temporal patterns","volume":"91","author":"R Teghtsoonian","year":"1978","journal-title":"The American Journal of Psychology"},{"issue":"6","key":"pone.0290137.ref015","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1002\/mrm.22505","article-title":"Sensory and motor stimulation thresholds of the ulnar nerve from electric and magnetic field stimuli: implications to gradient coil operation","volume":"64","author":"BJ Recoskie","year":"2010","journal-title":"Magn Reson Med"},{"issue":"3","key":"pone.0290137.ref016","doi-asserted-by":"crossref","first-page":"197","DOI":"10.2217\/pmt.14.13","article-title":"Using TENS for pain control: the state of the evidence","volume":"4","author":"CG Vance","year":"2014","journal-title":"Pain Manag"},{"issue":"10","key":"pone.0290137.ref017","article-title":"Using TENS for Pain Control: Update on the State of the Evidence.","volume":"58","author":"CGT Vance","year":"2022","journal-title":"Medicina (Kaunas)."},{"issue":"5","key":"pone.0290137.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3138\/ptc.2015-88","article-title":"Neuromuscular Electrical Stimulation for Treatment of Muscle Impairment: Critical Review and Recommendations for Clinical Practice.","volume":"69","author":"EL Nussbaum","year":"2017","journal-title":"Physiother Can."},{"issue":"3 Suppl","key":"pone.0290137.ref019","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.pain.2010.09.030","article-title":"Central sensitization: implications for the diagnosis and treatment of pain","volume":"152","author":"CJ Woolf","year":"2011","journal-title":"Pain"},{"issue":"6","key":"pone.0290137.ref020","first-page":"463","article-title":"Transcranial direct current stimulation\u2014update 2011.","volume":"29","author":"MA Nitsche","year":"2011","journal-title":"Restor Neurol Neurosci"},{"key":"pone.0290137.ref021","doi-asserted-by":"crossref","first-page":"317","DOI":"10.3389\/fnhum.2013.00317","article-title":"Transcranial alternating current stimulation (tACS).","volume":"7","author":"A Antal","year":"2013","journal-title":"Front Hum Neurosci"},{"issue":"52","key":"pone.0290137.ref022","doi-asserted-by":"crossref","first-page":"14147","DOI":"10.1523\/JNEUROSCI.4248-08.2008","article-title":"Increasing human brain excitability by transcranial high-frequency random noise stimulation","volume":"28","author":"D Terney","year":"2008","journal-title":"J Neurosci"},{"issue":"6","key":"pone.0290137.ref023","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1111\/j.1526-4637.2007.00282.x","article-title":"Age interacts with stimulus frequency in the temporal summation of pain","volume":"8","author":"M Farrell","year":"2007","journal-title":"Pain Med"},{"issue":"2","key":"pone.0290137.ref024","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1113\/jphysiol.1968.sp008469","article-title":"The role of calcium in neuromuscular facilitation","volume":"195","author":"B Katz","year":"1968","journal-title":"J Physiol"},{"issue":"4","key":"pone.0290137.ref025","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1113\/jphysiol.1952.sp004764","article-title":"A quantitative description of membrane current and its application to conduction and excitation in nerve","volume":"117","author":"AL Hodgkin","year":"1952","journal-title":"J Physiol"},{"issue":"2","key":"pone.0290137.ref026","doi-asserted-by":"crossref","first-page":"e12955","DOI":"10.1111\/obr.12955","article-title":"A systematic review of body mass gain after deep brain stimulation of the subthalamic nucleus in patients with Parkinson\u2019s disease","volume":"21","author":"J Steinhardt","year":"2020","journal-title":"Obes Rev"},{"key":"pone.0290137.ref027","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.neuropsychologia.2014.09.035","article-title":"One hand or the other? Effector selection biases in right and left handers","volume":"64","author":"JC Main","year":"2014","journal-title":"Neuropsychologia"},{"issue":"3","key":"pone.0290137.ref028","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1089\/brain.2020.0949","article-title":"The Effects of Monophasic Anodal Transcranial Pulsed Current Stimulation on Corticospinal Excitability and Motor Performance in Healthy Young Adults: A Randomized Double-Blinded Sham-Controlled Study","volume":"12","author":"T Dissanayaka","year":"2022","journal-title":"Brain Connect"},{"issue":"12","key":"pone.0290137.ref029","doi-asserted-by":"crossref","first-page":"4908","DOI":"10.1111\/ejn.14916","article-title":"The effects of a single-session cathodal transcranial pulsed current stimulation on corticospinal excitability: A randomized sham-controlled double-blinded study","volume":"52","author":"T Dissanayaka","year":"2020","journal-title":"Eur J Neurosci"},{"issue":"9","key":"pone.0290137.ref030","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1089\/brain.2020.0756","article-title":"The Effect of Transcranial Pulsed Current Stimulation at 4 and 75 Hz on Electroencephalography Theta and High Gamma Band Power: A Pilot Study.","volume":"10","author":"T Dissanayaka","year":"2020","journal-title":"Brain Connect"},{"issue":"7","key":"pone.0290137.ref031","doi-asserted-by":"crossref","first-page":"e0131779","DOI":"10.1371\/journal.pone.0131779","article-title":"Anodal Transcranial Pulsed Current Stimulation: The Effects of Pulse Duration on Corticospinal Excitability.","volume":"10","author":"S Jaberzadeh","year":"2015","journal-title":"PLoS One."},{"issue":"2","key":"pone.0290137.ref032","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.clinph.2013.08.025","article-title":"Anodal transcranial pulsed current stimulation: A novel technique to enhance corticospinal excitability.","volume":"125","author":"S Jaberzadeh","year":"2014","journal-title":"Clin Neurophysiol"},{"issue":"3","key":"pone.0290137.ref033","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/ner.12574","article-title":"Safety Review of Transcranial Direct Current Stimulation in Stroke.","volume":"20","author":"C Russo","year":"2017","journal-title":"Neuromodulation"},{"key":"pone.0290137.ref034","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.concog.2017.10.015","article-title":"The neuropsychophysiology of tingling.","volume":"58","author":"BT Tihanyi","year":"2018","journal-title":"Conscious Cogn"},{"key":"pone.0290137.ref035","first-page":"272","article-title":"Pain perception.","volume":"48","author":"R. Melzack","year":"1970","journal-title":"Res Publ Assoc Res Nerv Ment Dis"},{"key":"pone.0290137.ref036","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/scientificamerican0261-41","article-title":"The perception of pain","volume":"204","author":"R. Melzack","year":"1961","journal-title":"Sci Am"},{"key":"pone.0290137.ref037","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3389\/fnhum.2017.00146","article-title":"Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.","volume":"11","author":"R Sasaki","year":"2017","journal-title":"Front Hum Neurosci."},{"issue":"6","key":"pone.0290137.ref038","doi-asserted-by":"crossref","first-page":"e0129034","DOI":"10.1371\/journal.pone.0129034","article-title":"Evolution of Skin Temperature after the Application of Compressive Forces on Tendon, Muscle and Myofascial Trigger Point.","volume":"10","author":"MF Magalhaes","year":"2015","journal-title":"PLoS One."},{"key":"pone.0290137.ref039","doi-asserted-by":"crossref","first-page":"596159","DOI":"10.3389\/fphys.2020.596159","article-title":"Effect of Different Kinesio Taping Interventions on the Local Thresholds of Current Perception and Pressure Pain in Healthy Adults.","volume":"11","author":"K Liu","year":"2020","journal-title":"Front Physiol"},{"issue":"9","key":"pone.0290137.ref040","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1177\/1545968312448233","article-title":"Safety and immediate effect of noninvasive transcranial pulsed current stimulation on gait and balance in Parkinson disease","volume":"26","author":"G Alon","year":"2012","journal-title":"Neurorehabil Neural Repair"},{"issue":"6","key":"pone.0290137.ref041","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1152\/jn.00456.2022","article-title":"Strength-duration properties and excitability of motor and sensory axons across different target thresholds","volume":"129","author":"Y Shimatani","year":"2023","journal-title":"J Neurophysiol"},{"issue":"5","key":"pone.0290137.ref042","doi-asserted-by":"crossref","first-page":"e0125609","DOI":"10.1371\/journal.pone.0125609","article-title":"Dynamic impedance model of the skin-electrode interface for transcutaneous electrical stimulation.","volume":"10","author":"JL Vargas Luna","year":"2015","journal-title":"PLoS One"},{"issue":"12","key":"pone.0290137.ref043","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1007\/s10409-020-01026-2","article-title":"Effects of electrical stimulation on skin surface.","volume":"37","author":"X Xu","year":"2021","journal-title":"Acta Mech Sin"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0290137","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T18:27:48Z","timestamp":1702492068000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0290137"}},"subtitle":[],"editor":[{"given":"Thiago P.","family":"Fernandes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,12,13]]},"references-count":43,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0290137","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,13]]}}}