{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:20:03Z","timestamp":1789957203210,"version":"4.0.1"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019550","name":"Laureate Institute for Brain Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019550","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mal de Debarquement Balance Disorders Foundation"},{"DOI":"10.13039\/100001380","name":"William K Warren Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001380","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM121312"],"award-info":[{"award-number":["P20 GM121312"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Springbank Foundation"},{"DOI":"10.13039\/501100008982","name":"National Science Foundation","doi-asserted-by":"publisher","award":["RII Track-2 #1539068"],"award-info":[{"award-number":["RII Track-2 #1539068"]}],"id":[{"id":"10.13039\/501100008982","id-type":"DOI","asserted-by":"publisher"}]}],"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>Mal de D\u00e9barquement Syndrome (MdDS) is a medically refractory neurotological disorder characterized by persistent oscillating vertigo that follows a period of entrainment to oscillating motion such as experienced during sea or air travel. Fronto-occipital hypersynchrony may correlate with MdDS symptom severity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>Individuals with treatment refractory MdDS lasting at least 6 months received single administrations of three fronto-occipital transcranial alternating current stimulation (tACS) protocols in an \u201cn-of-1\u201d double-blind randomized design: alpha frequency anti-phase, alpha-frequency in-phase, and gamma frequency control. Baseline assessments were made on Day 1. The treatment protocol that led to the most acute reduction in symptoms during a test session on Day 2 was administered for 10\u201312 stacked sessions given on Days 3 through 5 (20-minutes at 2-4mA). Pre to post symptom changes were assessed on Day 1 and Day 5. Participants who could clearly choose a preferred protocol on Day 2 did better on Day 5 than those who could not make a short-term determination on Day 2 and either chose a protocol based on minimized side effects or were randomized to one of the three protocols. In addition, weekly symptom assessments were made for four baseline and seven post stimulation points for the Dizziness Handicap Inventory (DHI), MdDS Balance Rating Scale (MBRS), and Hospital Anxiety and Depression Scale (HADS).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Of 24 participants, 13 chose anti-phase, 7 chose in-phase, and 4 chose control stimulation. Compared to baseline, 10\/24 completers noted \u2265 25% reduction, 5\/24 \u226550% reduction, and 2\/24 \u226575% reduction in oscillating vertigo intensity from Day 1 to Day 5. Stimulating at a frequency slightly higher than the individual alpha frequency (IAF) was better than stimulating at exactly the IAF, and slightly better than stimulating with a strategy of standardized stimulation at 10Hz. A one-way repeated measures ANOVA of weekly DHI, MBRS, and HADS measurements showed significant reductions immediately after treatment with improvement increasing through post-treatment week 6.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Fronto-occipital tACS may be effective in reducing the oscillating vertigo of MdDS and serve as a portable neuromodulation alternative for longer-term treatment. Stimulation frequency relative to the IAF may be important in determining the optimum treatment protocol [ClinicalTrials.gov study NCT02540616. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02540616\" xlink:type=\"simple\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02540616<\/jats:ext-link>].<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0263558","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T18:32:22Z","timestamp":1643999542000},"page":"e0263558","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Double-blind randomized N-of-1 trial of transcranial alternating current stimulation for mal de d\u00e9barquement syndrome"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3804-0879","authenticated-orcid":true,"given":"Yoon-Hee","family":"Cha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diamond","family":"Gleghorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Chipper","family":"Doudican","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"issue":"5","key":"pone.0263558.ref001","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1055\/s-0029-1241038","article-title":"Mal de debarquement.","volume":"29","author":"YH Cha","year":"2009","journal-title":"Semin Neurol"},{"issue":"4","key":"pone.0263558.ref002","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0196-0709(87)80007-8","article-title":"Persistent mal de debarquement syndrome: a motion-induced subjective disorder of balance.","volume":"8","author":"JJ Brown","year":"1987","journal-title":"Am J Otolaryngol"},{"issue":"7","key":"pone.0263558.ref003","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1007\/s00415-008-0837-3","article-title":"Clinical features and associated syndromes of mal de debarquement","volume":"255","author":"YH Cha","year":"2008","journal-title":"J Neurol"},{"issue":"6","key":"pone.0263558.ref004","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1001\/archotol.125.6.615","article-title":"Mal de debarquement","volume":"125","author":"TC Hain","year":"1999","journal-title":"Arch Otolaryngol Head Neck Surg"},{"issue":"14","key":"pone.0263558.ref005","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1177\/0333102413487999","article-title":"Rocking dizziness and headache: a two-way street.","volume":"33","author":"YH Cha","year":"2013","journal-title":"Cephalalgia"},{"key":"pone.0263558.ref006","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3389\/fneur.2018.00261","article-title":"Comprehensive Clinical Profile of Mal De Debarquement Syndrome.","volume":"9","author":"YH Cha","year":"2018","journal-title":"Front Neurol."},{"issue":"7","key":"pone.0263558.ref007","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1007\/s00415-011-6349-6","article-title":"Social, societal, and economic burden of mal de debarquement syndrome","volume":"259","author":"A Macke","year":"2012","journal-title":"J Neurol"},{"issue":"7","key":"pone.0263558.ref008","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1177\/1359105314553046","article-title":"The relationship between symptom severity, stigma, illness intrusiveness and depression in Mal de Debarquement Syndrome.","volume":"21","author":"MA Arroll","year":"2016","journal-title":"J Health Psychol"},{"issue":"6","key":"pone.0263558.ref009","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1007\/s10548-018-0671-6","article-title":"Electrophysiological Signatures of Intrinsic Functional Connectivity Related to rTMS Treatment for Mal de Debarquement Syndrome","volume":"31","author":"YH Cha","year":"2018","journal-title":"Brain Topogr"},{"issue":"4","key":"pone.0263558.ref010","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/brain.2018.0647","article-title":"Multimodal Imaging of Repetitive Transcranial Magnetic Stimulation Effect on Brain Network: A Combined Electroencephalogram and Functional Magnetic Resonance Imaging Study.","volume":"9","author":"Y Chen","year":"2019","journal-title":"Brain Connect"},{"issue":"11","key":"pone.0263558.ref011","doi-asserted-by":"crossref","first-page":"e49560","DOI":"10.1371\/journal.pone.0049560","article-title":"Metabolic and functional connectivity changes in mal de debarquement syndrome.","volume":"7","author":"YH Cha","year":"2012","journal-title":"PLoS One"},{"issue":"7","key":"pone.0263558.ref012","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1109\/TBME.2014.2313575","article-title":"Lasting modulation effects of rTMS on neural activity and connectivity as revealed by resting-state EEG","volume":"61","author":"L Ding","year":"2014","journal-title":"IEEE Trans Biomed Eng"},{"issue":"9","key":"pone.0263558.ref013","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1089\/brain.2017.0514","article-title":"Resting State Functional Connectivity Signature of Treatment Effects of Repetitive Transcranial Magnetic Stimulation in Mal de Debarquement Syndrome","volume":"7","author":"H Yuan","year":"2017","journal-title":"Brain Connect"},{"issue":"2","key":"pone.0263558.ref014","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ijpsycho.2005.10.004","article-title":"Genetic variation of individual alpha frequency (IAF) and alpha power in a large adolescent twin sample.","volume":"61","author":"CM Smit","year":"2006","journal-title":"Int J Psychophysiol"},{"issue":"6","key":"pone.0263558.ref015","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1111\/psyp.12043","article-title":"Peak individual alpha frequency qualifies as a stable neurophysiological trait marker in healthy younger and older adults.","volume":"50","author":"TH Grandy","year":"2013","journal-title":"Psychophysiology"},{"key":"pone.0263558.ref016","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.neuroimage.2014.01.049","article-title":"Inter- and intra-individual variability in alpha peak frequency.","volume":"92","author":"S Haegens","year":"2014","journal-title":"Neuroimage"},{"key":"pone.0263558.ref017","first-page":"10","article-title":"Individual alpha peak frequency is related to latent factors of general cognitive abilities.","volume":"79","author":"TH Grandy","year":"2013","journal-title":"NeuroimageEpub 2013"},{"issue":"12","key":"pone.0263558.ref018","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1007\/s00221-019-05666-0","article-title":"Current challenges: the ups and downs of tACS","volume":"237","author":"NS Bland","year":"2019","journal-title":"Exp Brain Res"},{"key":"pone.0263558.ref019","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fncel.2017.00214","article-title":"Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols.","volume":"11","author":"AV Tavakoli","year":"2017","journal-title":"Front Cell Neurosci"},{"key":"pone.0263558.ref020","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"},{"key":"pone.0263558.ref021","article-title":"Transcranial Alternating Current Stimulation Reduces Network Hypersynchrony and Persistent Vertigo.","author":"S Ahn","year":"2021","journal-title":"Neuromodulation"},{"issue":"9","key":"pone.0263558.ref022","doi-asserted-by":"crossref","first-page":"e928","DOI":"10.1097\/MAO.0000000000002341","article-title":"Occipital and Cerebellar Theta Burst Stimulation for Mal De Debarquement Syndrome","volume":"40","author":"YH Cha","year":"2019","journal-title":"Otol Neurotol"},{"issue":"6","key":"pone.0263558.ref023","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1097\/MAO.0000000000001045","article-title":"Double-Blind Sham-Controlled Crossover Trial of Repetitive Transcranial Magnetic Stimulation for Mal de Debarquement Syndrome","volume":"37","author":"YH Cha","year":"2016","journal-title":"Otol Neurotol"},{"issue":"2","key":"pone.0263558.ref024","first-page":"135","article-title":"Validation of measures from the smartphone sway balance application: a pilot study","volume":"9","author":"JA Patterson","year":"2014","journal-title":"Int J Sports Phys Ther"},{"issue":"4","key":"pone.0263558.ref025","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.brs.2016.03.016","article-title":"Randomized Single Blind Sham Controlled Trial of Adjunctive Home-Based tDCS after rTMS for Mal De Debarquement Syndrome: Safety, Efficacy, and Participant Satisfaction Assessment","volume":"9","author":"YH Cha","year":"2016","journal-title":"Brain Stimul"},{"issue":"4","key":"pone.0263558.ref026","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1001\/archotol.1990.01870040046011","article-title":"The development of the Dizziness Handicap Inventory","volume":"116","author":"GP Jacobson","year":"1990","journal-title":"Arch Otolaryngol Head Neck Surg"},{"issue":"6","key":"pone.0263558.ref027","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1600-0447.1983.tb09716.x","article-title":"The hospital anxiety and depression scale.","volume":"67","author":"AS Zigmond","year":"1983","journal-title":"Acta Psychiatr Scand"},{"issue":"4","key":"pone.0263558.ref028","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3233\/VES-170622","article-title":"Diagnostic criteria for persistent postural-perceptual dizziness (PPPD): Consensus document of the committee for the Classification of Vestibular Disorders of the Barany Society.","volume":"27","author":"JP Staab","year":"2017","journal-title":"J Vestib Res"},{"issue":"4","key":"pone.0263558.ref029","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3233\/VES-2012-0453","article-title":"Vestibular migraine: diagnostic criteria.","volume":"22","author":"T Lempert","year":"2012","journal-title":"J Vestib Res"},{"key":"pone.0263558.ref030","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/B978-0-444-63437-5.00027-3","article-title":"Motion sickness.","volume":"137","author":"JF Golding","year":"2016","journal-title":"Handb Clin Neurol"},{"issue":"5","key":"pone.0263558.ref031","first-page":"1142","article-title":"Less common neuro-otologic disorders.","volume":"18","author":"YH Cha","year":"2012","journal-title":"Continuum (Minneap Minn)"},{"issue":"6","key":"pone.0263558.ref032","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1212\/01.wnl.0000175987.59991.3d","article-title":"al. e. Epidemiology of vestibular vertigo: a neurotologic survey of the general population","volume":"65","author":"HK Neuhauser","year":"2005","journal-title":"Neurology"},{"issue":"6","key":"pone.0263558.ref033","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1212\/01.wnl.0000237539.09942.06","article-title":"Migrainous vertigo: prevalence and impact on quality of life","volume":"67","author":"HK Neuhauser","year":"2006","journal-title":"Neurology"},{"issue":"3","key":"pone.0263558.ref034","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1080\/17437199.2017.1343680","article-title":"Dynamic modelling of n-of-1 data: powerful and flexible data analytics applied to individualised studies.","volume":"11","author":"R Vieira","year":"2017","journal-title":"Health Psychol Rev"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0315783","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000}}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0263558","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T20:05:20Z","timestamp":1672776320000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0263558"}},"subtitle":[],"editor":[{"given":"Sandra","family":"Carvalho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0263558","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pone.0315783","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,4]]}}}