{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:48:19Z","timestamp":1778622499272,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011184","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,6,7]],"date-time":"2023-06-07T00:00:00Z","timestamp":1686096000000}}],"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["759998"],"award-info":[{"award-number":["759998"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["197271"],"award-info":[{"award-number":["197271"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Peripheral nerve stimulation is being investigated as a therapeutic tool in several clinical scenarios. However, the adopted devices have restricted ability to obtain desired outcomes with tolerable off-target effects. Recent promising solutions are not yet employed in clinical practice due to complex required surgeries, lack of long-term stability, and implant invasiveness. Here, we aimed to design a neural interface to address these issues, specifically dimensioned for pudendal and sacral nerves to potentially target sexual, bladder, or bowel dysfunctions. We designed the adaptable intrafascicular radial electrode (AIR) through realistic computational models. They account for detailed human anatomy, inhomogeneous anisotropic conductance, following the trajectories of axons along curving and branching fascicles, and detailed biophysics of axons. The model was validated against available experimental data. Thanks to computationally efficient geometry-based selectivity estimations we informed the electrode design, optimizing its dimensions to obtain the highest selectivity while maintaining low invasiveness. We then compared the AIR with state-of-the-art electrodes, namely InterStim leads, multipolar cuffs and transversal intrafascicular multichannel electrodes (TIME). AIR, comprising a flexible substrate, surface active sites, and radially inserted intrafascicular needles, is designed to be implanted in a few standard steps, potentially enabling fast implants. It holds potential for repeatable stimulation outcomes thanks to its radial structural symmetry. When compared in-silico, AIR consistently outperformed cuff electrodes and InterStim leads in terms of recruitment threshold and stimulation selectivity. AIR performed similarly or better than a TIME, with quantified less invasiveness. Finally, we showed how AIR can adapt to different nerve sizes and varying shapes while maintaining high selectivity. The AIR electrode shows the potential to fill a clinical need for an effective peripheral nerve interface. Its high predicted performance in all the identified requirements was enabled by a model-based approach, readily applicable for the optimization of electrode parameters in any peripheral nerve stimulation scenario.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011184","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T17:44:55Z","timestamp":1685036695000},"page":"e1011184","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Design of an adaptable intrafascicular electrode (AIR) for selective nerve stimulation by model-based optimization"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8325-330X","authenticated-orcid":true,"given":"Federico","family":"Ciotti","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4095-0233","authenticated-orcid":true,"given":"Andrea","family":"Cimolato","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-8007","authenticated-orcid":true,"given":"Giacomo","family":"Valle","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-9051","authenticated-orcid":true,"given":"Stanisa","family":"Raspopovic","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"pcbi.1011184.ref001","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/WNP.0b013e3181d64d8a","article-title":"Overview of the Clinical Applications of Vagus Nerve Stimulation","volume":"27","author":"JP Beekwilder","year":"2010","journal-title":"Journal of Clinical Neurophysiology"},{"key":"pcbi.1011184.ref002","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1016\/j.juro.2007.07.032","article-title":"Results of Sacral Neuromodulation Therapy for Urinary Voiding Dysfunction: Outcomes of a Prospective, Worldwide Clinical Study","volume":"178","author":"PEV van Kerrebroeck","year":"2007","journal-title":"Journal of Urology"},{"key":"pcbi.1011184.ref003","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1126\/science.abb1073","article-title":"Advancing limb neural prostheses","volume":"370","author":"S. 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