{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:24:39Z","timestamp":1772119479274,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["JARO"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Meniere\u2019s disease (MD) is a condition of the inner ear with symptoms affecting both vestibular and hearing functions. Some patients with MD experience vestibular drop attacks (VDAs), which are violent falls caused by spurious vestibular signals from the utricle and\/or saccule. Recent surgical work has shown that patients who experience VDAs also show disrupted utricular otolithic membranes. The objective of this study is to determine if otolithic membrane damage alone is sufficient to induce spurious vestibular signals, thus potentially eliciting VDAs and the vestibular dysfunction seen in patients with MD. We use a previously developed numerical model to describe the nonlinear dynamics of an array of active, elastically coupled hair cells. We then reduce the coupling strength of a selected region of the membrane to model the effects of tissue damage. As we reduce the coupling strength, we observe large and abrupt spikes in hair bundle position. As bundle displacements from the equilibrium position have been shown to lead to depolarization of the hair-cell soma and hence trigger neural activity, this spontaneous activity could elicit false detection of a vestibular signal. The results of this numerical model suggest that otolithic membrane damage alone may be sufficient to induce VDAs and the vestibular dysfunction seen in patients with MD. Future experimental work is needed to confirm these results in vitro.<\/jats:p>","DOI":"10.1007\/s10162-022-00880-0","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T13:11:32Z","timestamp":1671023492000},"page":"107-115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Vestibular Drop Attacks and Meniere\u2019s Disease as Results of Otolithic Membrane Damage\u2014A Numerical Model"],"prefix":"10.1007","volume":"24","author":[{"given":"Nicholas","family":"Senofsky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Faber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dolores","family":"Bozovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"880_CR1","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S0140-6736(08)61161-7","volume":"372","author":"H Sajjadi","year":"2008","unstructured":"Sajjadi H, Paparella MM (2008) Meniere\u2019s disease. The Lancet 372:406\u2013414","journal-title":"The Lancet"},{"key":"880_CR2","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1097\/MAO.0b013e318271c48b","volume":"33","author":"AP Calzada","year":"2012","unstructured":"Calzada AP, Lopez IA, Ishiyama G, Ishiyama A (2012) Otolithic membrane damage in patients with endolymphatic hydrops and drop attacks. Otol Neurotol 33:1593\u20131598","journal-title":"Otol Neurotol"},{"key":"880_CR3","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1111\/nyas.12699","volume":"1343","author":"G Ishiyama","year":"2015","unstructured":"Ishiyama G, Lopez IA, Sepahdari AR, Ishiyama A (2015) Meniere\u2019s disease: histopathology, cytochemistry, and imaging. Ann N Y Acad Sci 1343:49\u201357","journal-title":"Ann N Y Acad Sci"},{"key":"880_CR4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/j.neuron.2005.10.017","volume":"48","author":"M LeMasurier","year":"2005","unstructured":"LeMasurier M, Gillespie PG (2005) Hair-cell mechanotransduction and cochlear amplification. Neuron 48:403\u2013415","journal-title":"Neuron"},{"key":"880_CR5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.tins.2018.12.006","volume":"42","author":"inner-ear hair-cell mechanotransduction","year":"2019","unstructured":"inner-ear hair-cell mechanotransduction (2019) \u00d3 Maoil\u00e9idigh, D. & Ricci, A. J. A Bundle of mechanisms. Trends Neurosci 42:221\u2013236","journal-title":"Trends Neurosci"},{"key":"880_CR6","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1146\/annurev.neuro.29.051605.112917","volume":"30","author":"MA Vollrath","year":"2007","unstructured":"Vollrath MA, Kwan KY, Corey DP (2007) The micromachinery of mechanotransduction in hair cells. Annu Rev Neurosci 30:339\u2013365","journal-title":"Annu Rev Neurosci"},{"key":"880_CR7","doi-asserted-by":"publisher","first-page":"14386","DOI":"10.1073\/pnas.251530498","volume":"98","author":"P Martin","year":"2001","unstructured":"Martin P, Hudspeth AJ (2001) Compressive nonlinearity in the hair bundle\u2019s active response to mechanical stimulation. Proc Natl Acad Sci USA 98:14386\u201314391","journal-title":"Proc Natl Acad Sci USA"},{"key":"880_CR8","doi-asserted-by":"publisher","first-page":"14306","DOI":"10.1073\/pnas.96.25.14306","volume":"96","author":"P Martin","year":"1999","unstructured":"Martin P, Hudspeth AJ (1999) Active hair-bundle movements can amplify a hair cell\u2019s response to oscillatory mechanical stimuli. Proc Natl Acad Sci USA 96:14306\u201314311","journal-title":"Proc Natl Acad Sci USA"},{"key":"880_CR9","doi-asserted-by":"publisher","first-page":"5629","DOI":"10.1523\/JNEUROSCI.16-18-05629.1996","volume":"16","author":"ME Benser","year":"1996","unstructured":"Benser ME, Marquis RE, Hudspeth AJ (1996) Rapid, active hair bundle movements in hair cells from the bullfrog\u2019s sacculus. J Neurosci 16:5629\u20135643","journal-title":"J Neurosci"},{"key":"880_CR10","doi-asserted-by":"publisher","first-page":"4533","DOI":"10.1523\/JNEUROSCI.23-11-04533.2003","volume":"23","author":"P Martin","year":"2003","unstructured":"Martin P, Bozovic D, Choe Y, Hudspeth AJ (2003) Spontaneous oscillation by hair bundles of the bullfrog\u2019s sacculus. J Neurosci 23:4533\u20134548","journal-title":"J Neurosci"},{"key":"880_CR11","doi-asserted-by":"publisher","first-page":"14380","DOI":"10.1073\/pnas.251530598","volume":"98","author":"P Martin","year":"2001","unstructured":"Martin P, Hudspeth AJ, J\u00fclicher F (2001) Comparison of a hair bundle\u2019s spontaneous oscillations with its response to mechanical stimulation reveals the underlying active process. Proc Natl Acad Sci USA 98:14380\u201314385","journal-title":"Proc Natl Acad Sci USA"},{"key":"880_CR12","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1016\/j.bpj.2012.03.017","volume":"102","author":"L Fredrickson-Hemsing","year":"2012","unstructured":"Fredrickson-Hemsing L, Strimbu CE, Roongthumskul Y, Bozovic D (2012) Dynamics of freely oscillating and coupled hair cell bundles under mechanical deflection. Biophys J 102:1785\u20131792","journal-title":"Biophys J"},{"issue":"2","key":"880_CR13","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/0378-5955(93)90128-N","volume":"68","author":"ME Benser","year":"1993","unstructured":"Benser ME, Issa NP, Hudspeth AJ (1993) Hair-bundle stiffness dominates the elastic reactance to otolithic-membrane shear. Hear Res 68(2):243\u2013252","journal-title":"Hear Res"},{"issue":"1\u20132","key":"880_CR14","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/S0378-5955(00)00034-4","volume":"143","author":"A Kondrachuk","year":"2000","unstructured":"Kondrachuk A, v. (2000) Computer simulation of the mechanical stimulation of the saccular membrane of bullfrog. Hear Res 143(1\u20132):130\u2013138","journal-title":"Hear Res"},{"issue":"43","key":"880_CR15","doi-asserted-by":"publisher","first-page":"14457","DOI":"10.1523\/JNEUROSCI.1451-15.2015","volume":"35","author":"SWF Meenderink","year":"2015","unstructured":"Meenderink SWF, Quinones PM, Bozovic D (2015) Voltage-mediated control of spontaneous bundle oscillations in saccular hair cells. J Neurosci 35(43):14457\u201314466","journal-title":"J Neurosci"},{"issue":"5","key":"880_CR16","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1140\/epje\/i2012-12037-6","volume":"35","author":"K Dierkes","year":"2012","unstructured":"Dierkes K, J\u00fclicher F, Lindner B (2012) A mean-field approach to elastically coupled hair bundles. Eur Phys J E 35(5):37","journal-title":"Eur Phys J E"},{"key":"880_CR17","doi-asserted-by":"publisher","first-page":"12195","DOI":"10.1073\/pnas.0403020101","volume":"101","author":"B Nadrowski","year":"2004","unstructured":"Nadrowski B, Martin P, J\u00fclicher F (2004) Active hair-bundle motility harnesses noise to operate near an optimum of mechanosensitivity. Proc Natl Acad Sci USA 101:12195\u201312200","journal-title":"Proc Natl Acad Sci USA"},{"issue":"4","key":"880_CR18","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.97.042411","volume":"97","author":"S Ji","year":"2018","unstructured":"Ji S, Bozovic D, Bruinsma R (2018) Amphibian sacculus and the forced Kuramoto model with intrinsic noise and frequency dispersion. Phys Rev E 97(4):042411","journal-title":"Phys Rev E"},{"key":"880_CR19","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/S0896-6273(00)80184-1","volume":"17","author":"EN Yamoah","year":"1996","unstructured":"Yamoah EN, Gillespie PG (1996) Phosphate analogs block adaptation in hair cells by inhibiting adaptation-motor force production. Neuron 17:523\u2013533","journal-title":"Neuron"},{"key":"880_CR20","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.bpj.2011.06.027","volume":"101","author":"Y Roongthumskul","year":"2011","unstructured":"Roongthumskul Y, Fredrickson-Hemsing L, Kao A, Bozovic D (2011) Multiple-timescale dynamics underlying spontaneous oscillations of saccular hair bundles. Biophys J 101:603\u2013610","journal-title":"Biophys J"},{"key":"880_CR21","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1016\/j.bpj.2008.09.060","volume":"96","author":"D Ramunno-Johnson","year":"2009","unstructured":"Ramunno-Johnson D, Strimbu CE, Fredrickson L, Arisaka K, Bozovic D (2009) Distribution of frequencies of spontaneous oscillations in hair cells of the bullfrog sacculus. Biophys J 96:1159\u20131168","journal-title":"Biophys J"},{"key":"880_CR22","unstructured":"https:\/\/github.com\/NicholasSenofsky\/MD-VDA-Numerical-Model"},{"key":"880_CR23","doi-asserted-by":"crossref","unstructured":"Kim KJ, Ahn KH (2014) Amplitude death of coupled hair bundles with stochastic channel noise. Phys Rev E Stat Nonlin Soft Matter Phys 89(4):042703","DOI":"10.1103\/PhysRevE.89.042703"},{"issue":"6","key":"880_CR24","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1097\/AUD.0000000000000878","volume":"41","author":"P Roman-Naranjo","year":"2020","unstructured":"Roman-Naranjo P et al (2020) Burden of rare variants in the OTOG Gene in familial Meniere\u2019s disease. Ear Hear 41(6):1598\u20131605","journal-title":"Ear Hear"},{"key":"880_CR25","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/72793","volume":"24","author":"MC Simmler","year":"2000","unstructured":"Simmler MC et al (2000) Targeted disruption of Otog results in deafness and severe imbalance. Nat Genet 24:139\u2013143","journal-title":"Nat Genet"}],"container-title":["Journal of the Association for Research in Otolaryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10162-022-00880-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10162-022-00880-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10162-022-00880-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T10:19:25Z","timestamp":1677493165000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10162-022-00880-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["880"],"URL":"https:\/\/doi.org\/10.1007\/s10162-022-00880-0","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742582289.793598171","asserted-by":"object"}]},"ISSN":["1438-7573"],"issn-type":[{"value":"1438-7573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]},"assertion":[{"value":"20 February 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}