{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T12:26:57Z","timestamp":1742387217462,"version":"3.37.3"},"reference-count":51,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T00:00:00Z","timestamp":1687651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conseller\u00eda de Innovaci\u00f3n, Universidades, Ciencia y Sociedad Digital (Generalitat Valenciana, Spain)","award":["GVA-COVID19\/2021\/062"]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sensors"],"abstract":"A new pandemic was declared at the end of 2019 because of coronavirus disease 2019 (COVID-19). One of the effects of COVID-19 infection is anosmia (i.e., a loss of smell). Unfortunately, this olfactory dysfunction is persistent in around 5% of the world\u2019s population, and there is not an effective treatment for it yet. The aim of this paper is to describe a potential non-invasive neurostimulation strategy for treating persistent anosmia in post-COVID-19 patients. In order to design the neurostimulation strategy, 25 subjects who experienced anosmia due to COVID-19 infection underwent an olfactory assessment while their electroencephalographic (EEG) signals were recorded. These signals were used to investigate the activation of brain regions during the olfactory process and identify which regions would be suitable for neurostimulation. Afterwards, 15 subjects participated in the evaluation of the neurostimulation strategy, which was based on applying transcranial direct current stimulation (tDCS) in selected brain regions related to olfactory function. The results showed that subjects with lower scores in the olfactory assessment obtained greater improvement than the other subjects. Thus, tDCS could be a promising option for people who have not fully regained their sense of smell following COVID-19 infection.<\/jats:p>","DOI":"10.3390\/s23135880","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T09:28:02Z","timestamp":1687771682000},"page":"5880","source":"Crossref","is-referenced-by-count":4,"title":["Design and Evaluation of a Potential Non-Invasive Neurostimulation Strategy for Treating Persistent Anosmia in Post-COVID-19 Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8855-1151","authenticated-orcid":false,"given":"Desir\u00e9e I.","family":"Gracia","sequence":"first","affiliation":[{"name":"Brain-Machine Interface Systems Lab, Miguel Hernandez University of Elche, 03202 Elche, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-1554","authenticated-orcid":false,"given":"Mario","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Brain-Machine Interface Systems Lab, Miguel Hernandez University of Elche, 03202 Elche, Spain"},{"name":"Engineering Research Institute of Elche\u2014I3E, Miguel Hernandez University of Elche, 03202 Elche, Spain"}]},{"given":"Tatiana","family":"Candela","sequence":"additional","affiliation":[{"name":"Brain-Machine Interface Systems Lab, Miguel Hernandez University of Elche, 03202 Elche, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8057-5952","authenticated-orcid":false,"given":"Eduardo","family":"I\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"Brain-Machine Interface Systems Lab, Miguel Hernandez University of Elche, 03202 Elche, Spain"},{"name":"Engineering Research Institute of Elche\u2014I3E, Miguel Hernandez University of Elche, 03202 Elche, Spain"}]},{"given":"Rosa M.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario Dr. Balmis de Alicante, 03010 Alicante, Spain"},{"name":"Valencian Community Foundation for the Management of the Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4495-5736","authenticated-orcid":false,"given":"Carmina","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario Dr. Balmis de Alicante, 03010 Alicante, Spain"},{"name":"Valencian Community Foundation for the Management of the Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-9657","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Azor\u00edn","sequence":"additional","affiliation":[{"name":"Brain-Machine Interface Systems Lab, Miguel Hernandez University of Elche, 03202 Elche, Spain"},{"name":"Engineering Research Institute of Elche\u2014I3E, Miguel Hernandez University of Elche, 03202 Elche, Spain"},{"name":"Valencian Graduated School and Research Network of Artificial Intelligence\u2014ValGRAI, 46022 Valencia, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"622466","DOI":"10.3389\/fphys.2020.622466","article-title":"COVID-19-Associated Neurological Manifestations: An Emerging Electroencephalographic Literature","volume":"11","author":"Vellieux","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/epi4.12399","article-title":"EEG findings in acutely ill patients investigated for SARS-CoV-2\/COVID-19: A small case series preliminary report","volume":"5","author":"Galanopoulou","year":"2020","journal-title":"Epilepsia Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1016\/j.mayocp.2020.05.030","article-title":"Smell and Taste Dysfunction in Patients with COVID-19: A Systematic Review and Meta-analysis","volume":"95","author":"Agyeman","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1177\/01945998221097656","article-title":"Decreasing Incidence of Chemosensory Changes by COVID-19 Variant","volume":"168","author":"Coelho","year":"2022","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e069503","DOI":"10.1136\/bmj-2021-069503","article-title":"Prognosis and persistence of smell and taste dysfunction in patients with covid-19: Meta-analysis with parametric cure modelling of recovery curves","volume":"378","author":"Tan","year":"2022","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1111\/joim.13209","article-title":"Prevalence and 6-month recovery of olfactory dysfunction: A multicentre study of 1363 COVID-19 patients","volume":"290","author":"Lechien","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2680","DOI":"10.1002\/lary.29056","article-title":"COVID-19 Viral Load in the Severity of and Recovery From Olfactory and Gustatory Dysfunction","volume":"130","author":"Cho","year":"2020","journal-title":"Laryngoscope"},{"key":"ref_8","first-page":"1703","article-title":"Anosmia in COVID-19 associated with injury to the olfactory bulbs evident on MRI","volume":"41","author":"Leal","year":"2020","journal-title":"Am. J. Neuroradiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e3145","DOI":"10.1212\/WNL.0000000000010806","article-title":"Loss of smell in patients with COVID-19: MRI data reveal a transient edema of the olfactory clefts","volume":"95","author":"Eliezer","year":"2020","journal-title":"Neurology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1212\/WNL.0000000000009850","article-title":"Bilateral transient olfactory bulb edema during COVID-19-related anosmia","volume":"95","author":"Laurendon","year":"2020","journal-title":"Neurology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41593-020-00758-5","article-title":"Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19","volume":"24","author":"Meinhardt","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1002\/alr.22680","article-title":"Prevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID-19 patients","volume":"10","author":"Moein","year":"2020","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s40463-020-00423-8","article-title":"Early recovery following new onset anosmia during the COVID-19 pandemic\u2014An observational cohort study","volume":"49","author":"Hopkins","year":"2020","journal-title":"J. Otolaryngol.-Head Neck Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2115352","DOI":"10.1001\/jamanetworkopen.2021.15352","article-title":"Clinical Outcomes for Patients with Anosmia 1 Year after COVID-19 Diagnosis","volume":"4","author":"Renaud","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103607","DOI":"10.1016\/j.amjoto.2022.103607","article-title":"Recovery from Covid-19 smell loss: Two-years of follow up","volume":"43","author":"McWilliams","year":"2022","journal-title":"Am. J. Otolaryngol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e001256","DOI":"10.1136\/bmjopen-2012-001256","article-title":"Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: A population-based survey (OLFACAT study)","volume":"2","author":"Mullol","year":"2012","journal-title":"BMJ Open"},{"key":"ref_17","first-page":"513","article-title":"Anosmia\u2014A clinical review","volume":"42","author":"Boesveldt","year":"2017","journal-title":"Chem. Sci."},{"key":"ref_18","first-page":"e30425","article-title":"Management of Anosmia in COVID-19: A Comprehensive Review","volume":"14","author":"Khurana","year":"2022","journal-title":"Cureus"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Scaturro, D., Vitagliani, F., Di Bella, V.E., Falco, V., Tomasello, S., Lauricella, L., and Letizia Mauro, G. (2022). The Role of Acetyl-Carnitine and Rehabilitation in the Management of Patients with Post-COVID Syndrome: Case-Control Study. Appl. Sci., 12.","DOI":"10.3390\/app12084084"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1001\/archotol.1991.01870170065015","article-title":"Smell and Taste Disorders, A Study of 750 Patients From the University of Pennsylvania Smell and Taste Center","volume":"117","author":"Deems","year":"1991","journal-title":"Arch.-Otolaryngol. Head Neck Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/s41586-022-04569-5","article-title":"SARS-CoV-2 is associated with changes in brain structure in UK Biobank","volume":"604","author":"Douaud","year":"2022","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bhatia-Dey, N., and Heinbockel, T. (2021). The Olfactory System as Marker of Neurodegeneration in Aging, Neurological and Neuropsychiatric Disorders. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18136976"},{"key":"ref_23","first-page":"286","article-title":"Effects of electrical stimulation of the human olfactory mucosa","volume":"46","author":"Straschill","year":"1983","journal-title":"Appl. Neurophysiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"581503","DOI":"10.3389\/fnins.2020.581503","article-title":"Optimized Electrode Placements for Non-invasive Electrical Stimulation of the Olfactory Bulb and Olfactory Mucosa","volume":"14","author":"Cakmak","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Brooks, J., Teng, S.Y., Wen, J., Nith, R., Nishida, J., and Lopes, P. (2021, January 8\u201313). Stereo-Smell via Electrical Trigeminal Stimulation. Proceedings of the 2021 CHI Conference on Human Factors in Computing Systems, New York, NY, USA.","DOI":"10.1145\/3411764.3445300"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1109\/TBCAS.2022.3166530","article-title":"Gas Recognition in E-Nose System: A Review","volume":"16","author":"Chen","year":"2022","journal-title":"IEEE Trans. Biomed. Circuits Syst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/alr.22237","article-title":"Induction of smell through transethmoid electrical stimulation of the olfactory bulb","volume":"9","author":"Holbrook","year":"2019","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.clinph.2016.10.087","article-title":"Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS)","volume":"128","author":"Lefaucheur","year":"2017","journal-title":"Clin. Neurophysiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3109\/15622975.2013.876514","article-title":"Can transcranial direct current stimulation (tDCS) alleviate symptoms and improve cognition in psychiatric disorders?","volume":"15","author":"Mondino","year":"2014","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.neuroimage.2013.05.117","article-title":"Therapeutic effects of non-invasive brain stimulation with direct currents (tDCS) in neuropsychiatric diseases","volume":"85","author":"Kuo","year":"2014","journal-title":"NeuroImage"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fmed.2020.00372","article-title":"Randomized Controlled Study Evaluating Efficiency of Low Intensity Transcranial Direct Current Stimulation (tDCS) for Dyspnea Relief in Mechanically Ventilated COVID-19 Patients in ICU: The tDCS-DYSP-COVID Protocol","volume":"7","author":"Azabou","year":"2020","journal-title":"Front. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1590\/1806-9282.67.01.20200671","article-title":"Transcranial direct current stimulation as a strategy to manage COVID-19 pain and fatigue","volume":"67","author":"Moura","year":"2021","journal-title":"Rev. Assoc. M\u00e9d. Bras."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3389\/fnint.2020.00046","article-title":"Home-Based Transcranial Direct Current Stimulation (tDCS) to Prevent and Treat Symptoms Related to Stress: A Potential Tool to Remediate the Behavioral Consequences of the COVID-19 Isolation Measures?","volume":"14","author":"Fregni","year":"2020","journal-title":"Front. Integr. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.anorl.2015.08.004","article-title":"How to assess olfactory performance with the Sniffin\u2019 Sticks test","volume":"133","author":"Rumeau","year":"2016","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.anorl.2013.07.002","article-title":"Influence of random answers on interpretation of the Sniffing Stick identification test in nasal polyposis","volume":"132","author":"Eluecque","year":"2015","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s00405-018-5248-1","article-title":"Updated Sniffin\u2019 Sticks normative data based on an extended sample of 9139 subjects","volume":"276","author":"Oleszkiewicz","year":"2019","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Iravani, B., Arshamian, A., Ohla, K., Wilson, D.A., and Lundstr\u00f6m, J.N. (2020). Non-invasive recording from the human olfactory bulb. Nat. Commun., 648.","DOI":"10.1101\/660050"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/chemse\/22.1.77","article-title":"Olfactory Evoked Potential Produced by Electrical Stimulation of the Human Olfactory Mucosa","volume":"22","author":"Ishimaru","year":"1997","journal-title":"Chem. Senses"},{"key":"ref_39","unstructured":"Seta, N., Koizuka, I., Takemoto, I., Matsunaga, T., and Tonoike, M. (November, January 31). A Test Of Olfactory Evoked Potentials Using Odor Stimulation. Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Orlando, FL, USA."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3839","DOI":"10.1007\/s00405-021-06683-y","article-title":"Prognostic value of olfactory evoked potentials in patients with post-infectious olfactory dysfunction","volume":"278","author":"Guo","year":"2021","journal-title":"Eur. Arch.-Oto-Rhino-Laryngol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0013-4694(95)00055-4","article-title":"Olfactory event-related potentials in normal human subjects: Effects of age and gender","volume":"95","author":"Cui","year":"1995","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/chemse\/17.1.61","article-title":"Stimulus parameters and temporal evolution of the olfactory evoked potential in rats","volume":"17","author":"Evans","year":"1992","journal-title":"Chem. Senses"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Arpaia, P., Cataldo, A., Criscuolo, S., De Benedetto, E., Masciullo, A., and Schiavoni, R. (2022). Assessment and Scientific Progresses in the Analysis of Olfactory Evoked Potentials. Bioengineering, 9.","DOI":"10.3390\/bioengineering9060252"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Caminiti, F., De Salvo, S., De Cola, M.C., Russo, M., Bramanti, P., Marino, S., and Ciurleo, R. (2014). Detection of Olfactory Dysfunction Using Olfactory Event Related Potentials in Young Patients with Multiple Sclerosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103151"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Thielscher, A., Antunes, A., and Saturnino, G.B. (2015, January 25\u201329). Field modeling for transcranial magnetic stimulation: A useful tool to understand the physiological effects of TMS?. Proceedings of the 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Milan, Italy.","DOI":"10.1109\/EMBC.2015.7318340"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3389\/fnins.2018.00443","article-title":"Effects of Cathode Location and the Size of Anode on Anodal Transcranial Direct Current Stimulation Over the Leg Motor Area in Healthy Humans","volume":"12","author":"Foerster","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.brs.2016.06.004","article-title":"Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016","volume":"9","author":"Bikson","year":"2016","journal-title":"Brain Stimul."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/chemse\/bjg061","article-title":"Ratings of Overall Olfactory Function","volume":"28","author":"Landis","year":"2003","journal-title":"Chem. Senses"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1136\/jnnp-2022-329162","article-title":"Impact of tDCS on persistent COVID-19 olfactory dysfunction: A double-blind sham-controlled study","volume":"94","author":"Vestito","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_50","unstructured":"Moradi, K. (2022, June 10). Clinical Trial Protocol Evaluation of the Effectiveness of TDCS (Transcranial Direct Current Stimulation) in the Treatment of Hyposmia in Patients with COVID-19. Available online: https:\/\/www.irct.ir\/trial\/53545."},{"key":"ref_51","unstructured":"Gardner-O\u2019Kearny, W. (2023, June 12). SWFT\u2014Shapiro-Wilk\/Shapiro-Francia Tests. Available online: https:\/\/www.mathworks.com\/matlabcentral\/fileexchange\/88778-swft-shapiro-wilk-shapiro-francia-tests."}],"container-title":["Sensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8220\/23\/13\/5880\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T03:02:23Z","timestamp":1737169343000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8220\/23\/13\/5880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,25]]},"references-count":51,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["s23135880"],"URL":"https:\/\/doi.org\/10.3390\/s23135880","relation":{},"ISSN":["1424-8220"],"issn-type":[{"type":"electronic","value":"1424-8220"}],"subject":[],"published":{"date-parts":[[2023,6,25]]}}}