{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:41:34Z","timestamp":1772102494942,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous neurodegenerative disease in which bulbar involvement frequently affects speech and voice production. Although acoustic voice analysis can detect phonatory alterations in ALS, its ability to differentiate clinical phenotypes remains limited. This study investigated whether biomechanical voice parameters provide complementary information for characterizing bulbar involvement across bulbar-onset ALS (ALS-B) and spinal-onset ALS (ALS-S) and explored their association with clinical and functional measures. Methods: This cross-sectional observational study included 50 patients with ALS (20 ALS-B, 30 ALS-S) and 50 controls with non-neurological voice disorders. Sustained vowel phonation was analyzed using acoustic measures and biomechanical voice parameters derived from a standardized model of vocal fold vibration. Perceptual voice severity was assessed using the GRBAS scale, while functional status was evaluated with the ALS Functional Rating Scale\u2013Revised (ALSFRS-R) and the Barthel Index. Associations with clinical measures were explored in secondary analyses. Results: Compared with controls, ALS patients showed significant differences in acoustic measures and several biomechanical parameters related to glottal closure and vibratory stability. Biomechanical analysis revealed significant differences between ALS-B and ALS-S, particularly in parameters reflecting vibratory asymmetry, glottal tension and cycle-to-cycle instability. Unexpectedly, ALS-B showed greater perceptual voice severity and higher Barthel Index scores than ALS-S, while no differences were observed in global ALSFRS-R total scores. Conclusions: Biomechanical voice analysis appears to capture physiologically meaningful alterations in vocal fold function in ALS and provides complementary information for characterizing bulbar motor involvement across clinical phenotypes, particularly ALS-B disease. When combined with acoustic and clinical assessments, this approach may enhance the evaluation of bulbar involvement and functional status in ALS.<\/jats:p>","DOI":"10.3390\/medsci14010112","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T09:31:32Z","timestamp":1772098292000},"page":"112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomechanical Voice Parameters as Potential Biomarkers for Phenotype Differentiation in Amyotrophic Lateral Sclerosis: A Cross-Sectional Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9735-8601","authenticated-orcid":false,"given":"Margarita","family":"P\u00e9rez-Bonilla","sequence":"first","affiliation":[{"name":"Interlevel Clinical Management Unit of Physical Medicine and Rehabilitation, Reina Sofia University Hospital, Cordoba and Guadalquivir Health District, 14011 Cordoba, Spain"},{"name":"Department of the Applied Physics, Radiology and Physical Medicine, Faculty of Medicine and Nursing of C\u00f3rdoba, University of C\u00f3rdoba, 14004 Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6662-2932","authenticated-orcid":false,"given":"Marina","family":"Mora-Ortiz","sequence":"additional","affiliation":[{"name":"Maimonides Biomedical Research Institute of C\u00f3rdoba (IMIBIC), Reina Sof\u00eda University Hospital, University of C\u00f3rdoba, 14004 Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5566-8778","authenticated-orcid":false,"given":"Paola","family":"D\u00edaz-Borrego","sequence":"additional","affiliation":[{"name":"Physical Medicine & Rehabilitation, Virgen Macarena University Hospital, 41009 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5680-759X","authenticated-orcid":false,"given":"Mar\u00eda Nieves","family":"Mu\u00f1oz-Alcaraz","sequence":"additional","affiliation":[{"name":"Interlevel Clinical Management Unit of Physical Medicine and Rehabilitation, Reina Sofia University Hospital, Cordoba and Guadalquivir Health District, 14011 Cordoba, Spain"},{"name":"Maimonides Biomedical Research Institute of C\u00f3rdoba (IMIBIC), Reina Sof\u00eda University Hospital, University of C\u00f3rdoba, 14004 Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando J.","family":"Mayordomo-Riera","sequence":"additional","affiliation":[{"name":"Interlevel Clinical Management Unit of Physical Medicine and Rehabilitation, Reina Sofia University Hospital, Cordoba and Guadalquivir Health District, 14011 Cordoba, Spain"},{"name":"Department of the Applied Physics, Radiology and Physical Medicine, Faculty of Medicine and Nursing of C\u00f3rdoba, University of C\u00f3rdoba, 14004 Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eloy","family":"Girela-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Morphological and Sociosanitary Sciences, Faculty of Medicine and Nursing of C\u00f3rdoba, University of C\u00f3rdoba, 14004 Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1016\/S0140-6736(10)61156-7","article-title":"Amyotrophic lateral sclerosis","volume":"377","author":"Kiernan","year":"2011","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6534150","DOI":"10.1155\/2018\/6534150","article-title":"Maximizing the Survival of Amyotrophic Lateral Sclerosis Patients: Current Perspectives","volume":"2018","author":"Khairoalsindi","year":"2018","journal-title":"Neurol. Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3109\/17482960802379004","article-title":"Dysarthria in amyotrophic lateral sclerosis: A review","volume":"11","author":"Tomik","year":"2010","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0892-1997(97)80081-1","article-title":"Acoustic analysis of voice in individuals with amyotrophic lateral sclerosis and perceptually normal vocal quality","volume":"11","author":"Silbergleit","year":"1997","journal-title":"J. Voice"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1159\/000506259","article-title":"Voice-Based Classification of Amyotrophic Lateral Sclerosis: Where Are We and Where Are We Going? A Systematic Review","volume":"19","author":"Vieira","year":"2019","journal-title":"Neurodegener. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Milella, G., Sciancalepore, D., Cavallaro, G., Piccirilli, G., Nanni, A.G., Fraddosio, A., D\u2019Errico, E., Paolicelli, D., Fiorella, M.L., and Simone, I.L. (2023). Acoustic Voice Analysis as a Useful Tool to Discriminate Different ALS Phenotypes. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092439"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Pfohl, S.R., Kim, R.B., Coan, G.S., and Mitchell, C.S. (2018). Unraveling the Complexity of Amyotrophic Lateral Sclerosis Survival Prediction. Front. Neuroinform., 12.","DOI":"10.3389\/fninf.2018.00036"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","article-title":"The ALSFRS-R: A revised ALS functional rating scale that incorporates assessments of respiratory function","volume":"169","author":"Cedarbaum","year":"1999","journal-title":"J. Neurol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.enfcli.2017.12.001","article-title":"Validaci\u00f3n del \u00edndice de Barthel en la poblaci\u00f3n espa\u00f1ola","volume":"28","year":"2018","journal-title":"Enferm. Clin."},{"key":"ref_10","first-page":"173","article-title":"The Effect of Anchor Voices and Visible Speech in Training in the GRABS Scale of Perceptual Evaluation of Dysphonia","volume":"63","year":"2012","journal-title":"Acta Otorrinolaringol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool for Mild Cognitive Impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_12","first-page":"493","article-title":"Validaci\u00f3n del An\u00e1lisis Biomec\u00e1nico para el Cribado de Patolog\u00eda de la Voz","volume":"2","year":"2022","journal-title":"Int. J. Health Sci."},{"key":"ref_13","unstructured":"Boersma, P., and Weenink, D. (2019, June 19). Praat: Doing Phonetics by Computer [Computer Program] 2022. (1999\u20132022). Available online: https:\/\/www.praat.org."},{"key":"ref_14","unstructured":"R Core Team R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.R-project.org\/."},{"key":"ref_15","unstructured":"IBM Corp (2023). IBM SPSS Statistics for Windows, IBM Corp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/14015439.2019.1687748","article-title":"Acoustic analysis of voice in bulbar amyotrophic lateral sclerosis: A systematic review and meta-analysis of studies","volume":"45","author":"Chiaramonte","year":"2019","journal-title":"Logop. Phoniatr. Vocology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12938-023-01174-z","article-title":"Detecting bulbar amyotrophic lateral sclerosis (ALS) using automatic acoustic analysis","volume":"23","author":"Simmatis","year":"2024","journal-title":"Biomed. Eng. OnLine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105706","DOI":"10.1016\/j.bspc.2023.105706","article-title":"Precision medicine in ALS: Identification of new acoustic markers for dysarthria severity assessment","volume":"89","author":"Dubbioso","year":"2024","journal-title":"Biomed. Signal Process. Control"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tena, A., Clari\u00e0, F., Solsona, F., and Povedano, M. (2022). Detecting Bulbar Involvement in Patients with Amyotrophic Lateral Sclerosis Based on Phonatory and Time-Frequency Features. Sensors, 22.","DOI":"10.3390\/s22031137"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Bonilla, M., D\u00edaz Borrego, P., Mora-Ortiz, M., Fern\u00e1ndez-Baillo, R., Mu\u00f1oz-Alcaraz, M.N., Mayordomo-Riera, F.J., and Girela L\u00f3pez, E. (2025). Relationship Between Voice Analysis and Functional Status in Patients with Amyotrophic Lateral Sclerosis. Audiol. Res., 15.","DOI":"10.3390\/audiolres15030053"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jvoice.2006.01.008","article-title":"Evaluation of Voice Pathology Based on the Estimation of Vocal Fold Biomechanical Parameters","volume":"21","author":"Nieto","year":"2007","journal-title":"J. Voice"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1159\/000533289","article-title":"Biomechanical Parameters of Voice in Parkinson\u2019s Disease Patients","volume":"76","year":"2024","journal-title":"Folia Phoniatr. Logop."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Stipancic, K.L., Yunusova, Y., Campbell, T.F., Wang, J., Berry, J.D., and Green, J.R. (2021). Two Distinct Clinical Phenotypes of Bulbar Motor Impairment in Amyotrophic Lateral Sclerosis. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.664713"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e89212","DOI":"10.5209\/rlog.89212","article-title":"An\u00e1lisis biomec\u00e1nico de la voz y percepci\u00f3n de la capacidad vocal como herramientas para la detecci\u00f3n de dificultades vocales en el alumnado y profesorado universitario y de interpretaci\u00f3n vocal","volume":"14","year":"2024","journal-title":"Rev. Investig. Logop."}],"container-title":["Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/1\/112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T09:54:45Z","timestamp":1772099685000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3271\/14\/1\/112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["medsci14010112"],"URL":"https:\/\/doi.org\/10.3390\/medsci14010112","relation":{},"ISSN":["2076-3271"],"issn-type":[{"value":"2076-3271","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}