{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T21:35:36Z","timestamp":1789594536049,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: Tactile gnosis derives from the interplay between the hand\u2019s tactile input and the memory systems of the brain. It is the prerequisite for complex hand functions. Impaired sensation leads to profound disability. Various invasive and non-invasive sensory substitution strategies for providing feedback from prostheses have been unsuccessful when translated to clinical practice, since they fail to match the feeling to genuine sensation of the somatosensory cortex. Methods: Herein, we describe a novel surgical technique for upper-limb-targeted sensory reinnervation (ulTSR) and report how single digital nerves selectively reinnervate the forearm skin and restore the spatial sensory capacity of single digits of the amputated hand in a case series of seven patients. We explore the interplay of the redirected residual digital nerves and the interpretation of sensory perception after reinnervation of the forearm skin in the somatosensory cortex by evaluating sensory nerve action potentials (SNAPs), somatosensory evoked potentials (SEPs), and amputation-associated pain qualities. Results: Digital nerves were rerouted and reliably reinnervated the forearm skin after hand amputation, leading to somatotopy and limb maps of the thumb and four individual fingers. SNAPs were obtained from the donor digital nerves after stimulating the recipient sensory nerves of the forearm. Matching SEPs were obtained after electrocutaneous stimulation of the reinnervated skin areas of the forearm where the thumb, index, and little fingers are perceived. Pain incidence was significantly reduced or even fully resolved. Conclusions: We propose that ulTSR can lead to higher acceptance of prosthetic hands and substantially reduce the incidence of phantom limb and neuroma pain. In addition, the spatial restoration of lost-hand sensing and the somatotopic reinnervation of the forearm skin may serve as a machine interface, allowing for genuine sensation and embodiment of the prosthetic hand without the need for complex neural coding adjustments.<\/jats:p>","DOI":"10.3390\/jcm14020417","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T08:03:05Z","timestamp":1736496185000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0671-4384","authenticated-orcid":false,"given":"Alexander","family":"Gardetto","sequence":"first","affiliation":[{"name":"Division of Plastic, Aesthetic and Reconstructive Surgery with Hand Surgery, Brixsana Private Clinic, Julius Durst 28, 39042 Bressanone, Italy"},{"name":"Clinic of Plastic, Reconstructive and Aesthetic Surgery, Padova University Hospital, Via Nicolo Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0087-3720","authenticated-orcid":false,"given":"Gernot R.","family":"M\u00fcller-Putz","sequence":"additional","affiliation":[{"name":"Institute of Neural Engineering, Graz University of Technology and BiotechMed Graz, Stremayrgasse 16\/4, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle R.","family":"Eberlin","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Bassetto","sequence":"additional","affiliation":[{"name":"Clinic of Plastic, Reconstructive and Aesthetic Surgery, Padova University Hospital, Via Nicolo Giustiniani 2, 35128 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane J.","family":"Atkins","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, 7200 Cambridge St Ste 10C, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-1295","authenticated-orcid":false,"given":"Mara","family":"Turri","sequence":"additional","affiliation":[{"name":"Stroke Unit, Department of Neurology, Bolzano General Hospital, Lorenz-B\u00f6hler-Str. 5, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-1423","authenticated-orcid":false,"given":"Gerfried","family":"Peternell","sequence":"additional","affiliation":[{"name":"Rehabilitation Clinic Tobelbad, Austrian Workers\u2019 Compensation Board (AUVA), Doktor-Georg-Neubauer-Str. 6, 8144 Tobelbad, Austria"},{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ortrun","family":"Neuper","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, Donaueschingenstr. 13, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/B978-0-444-53355-5.00005-1","article-title":"Sensory feedback for upper limb protheses","volume":"192","author":"Hsiao","year":"2011","journal-title":"Prog. Brain Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1302\/0301-620X.40B3.454","article-title":"Objective methods for determining the functional value of sensibility in the hand","volume":"40","author":"Moberg","year":"1958","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/978-1-4615-0713-0_45","article-title":"Dynamic use of tactile afferent signals in control of dexterous manipulation","volume":"508","author":"Johansson","year":"2002","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1093\/brain\/121.9.1603","article-title":"The perception of phantom limbs. The D. O. Hebb lecture","volume":"121","author":"Ramachandran","year":"1998","journal-title":"Brain J. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/nrn1991","article-title":"Phantom limb pain: A case of maladaptive CNS plasticity?","volume":"7","author":"Flor","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.neuroscience.2017.11.015","article-title":"Cortical plasticity as a basis of phantom limb pain: Fact or fiction?","volume":"387","author":"Andoh","year":"2018","journal-title":"Neuroscience"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1586\/erd.12.68","article-title":"Sensory feedback in upper limb prosthetics","volume":"10","author":"Antfolk","year":"2013","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0749-0712(21)00526-6","article-title":"Sensory substitution in prosthetics","volume":"17","author":"Lundborg","year":"2001","journal-title":"Hand Clin."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Peternell, G., Penasso, H., Luttenberger, H., Ronacher, H., Schlintner, R., Ashcraft, K., Gardetto, A., Ernst, J., and Kropiunig, U. (2023). Vibrotactile Feedback for a Person with Transradial Amputation and Visual Loss: A Case Report. Medicina, 59.","DOI":"10.3390\/medicina59101710"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sensinger, J.W., and Dosen, S. (2020). A Review of Sensory Feedback in Upper-Limb Prostheses from the Perspective of Human Motor Control. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00345"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41563-021-00966-9","article-title":"Sensory feedback for limb prostheses in amputees","volume":"20","author":"Raspopovic","year":"2021","journal-title":"Nat. Mater."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Simon, A.M., Turner, K.L., Miller, L.A., Dumanian, G.A., Potter, B.K., Beachler, M.D., Hargrove, L.J., and Kuiken, T.A. (2023). Myoelectric prosthesis hand grasp control following targeted muscle reinnervation in individuals with transradial amputation. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0280210"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/S0140-6736(07)60193-7","article-title":"Targeted reinnervation for enhanced prosthetic arm function in a woman with a proximal amputation: A case study","volume":"369","author":"Kuiken","year":"2007","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20061","DOI":"10.1073\/pnas.0706525104","article-title":"Redirection of cutaneous sensation from the hand to the chest skin of human amputees with targeted reinnervation","volume":"104","author":"Kuiken","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/brain\/awp082","article-title":"Sensory capacity of reinnervated skin after redirection of amputated upper limb nerves to the chest","volume":"132","author":"Marasco","year":"2009","journal-title":"Brain J. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.brainres.2008.11.039","article-title":"Vibrotactile detection thresholds for chest skin of amputees following targeted reinnervation surgery","volume":"1251","author":"Schultz","year":"2009","journal-title":"Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1109\/TNSRE.2013.2294907","article-title":"Novel targeted sensory reinnervation technique to restore functional hand sensation after transhumeral amputation","volume":"22","author":"Hebert","year":"2014","journal-title":"IEEE Trans. Neural Syst. Rehabil. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Schofield, J.S., Shell, C.E., Beckler, D.T., Thumser, Z.C., and Marasco, P.D. (2020). Long-Term Home-Use of Sensory-Motor-Integrated Bidirectional Bionic Prosthetic Arms Promotes Functional, Perceptual, and Cognitive Changes. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00120"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Osborn, L., Fifer, M., Moran, C., Betthauser, J., Armiger, R., Kaliki, R., and Thakor, N. (2017, January 19\u201321). Targeted Transcutaneous Electrical Nerve Stimulation for Phantom Limb Sensory Feedback. Proceedings of the 2017 IEEE Biomedical Circuits and Systems Conference (BioCAS), Turin, Italy.","DOI":"10.1109\/BIOCAS.2017.8325200"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gardetto, A., Baur, E.M., Prahm, C., Smekal, V., Jeschke, J., Peternell, G., Pedrini, M.T., and Kolbenschlag, J. (2021). Reduction of Phantom Limb Pain and Improved Proprioception through a TSR-Based Surgical Technique: A Case Series of Four Patients with Lower Limb Amputation. J. Clin. Med., 10.","DOI":"10.3390\/jcm10174029"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s41747-024-00495-5","article-title":"3D fascicular reconstruction of median and ulnar nerve: Initial experience and comparison between high-resolution ultrasound and MR microscopy","volume":"8","author":"Lechner","year":"2024","journal-title":"Eur. Radiol. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1177\/1558944716643290","article-title":"Intraneural Median Nerve Anatomy and Implications for Treating Mixed Median Nerve Injury in the Hand","volume":"11","author":"Franco","year":"2016","journal-title":"Hand"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.cps.2020.01.004","article-title":"Regenerative Peripheral Nerve Interfaces for Prevention and Management of Neuromas","volume":"47","author":"Santosa","year":"2020","journal-title":"Clin. Plast. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0006-8993(66)90056-4","article-title":"Evoked action potentials and conduction velocity in human sensory nerves","volume":"3","author":"Buchthal","year":"1966","journal-title":"Brain Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kobler, R.J., Sburlea, A.I., Mondini, V., and Muller-Putz, G.R. (2019, January 23\u201327). HEAR to remove pops and drifts: The high-variance electrode artifact removal (HEAR) algorithm. Proceedings of the 2019 41st Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), Berlin, Germany.","DOI":"10.1109\/EMBC.2019.8857742"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s44222-024-00151-y","article-title":"Mechanoneural interfaces for bionic integration","volume":"2","author":"Shu","year":"2024","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1177\/0309364616633919","article-title":"Cutaneous sensory outcomes from three transhumeral targeted reinnervation cases","volume":"40","author":"Hebert","year":"2016","journal-title":"Prosthet. Orthot. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1365-2133.1991.tb14790.x","article-title":"Anatomical mapping of Merkel cells in normal human adult epidermis","volume":"125","author":"Lacour","year":"1991","journal-title":"Br. J. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF02440956","article-title":"A myoelectrically-controlled prosthesis with sensory feedback","volume":"17","author":"Shannon","year":"1979","journal-title":"Med. Biol. Eng. Comput."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2993","DOI":"10.1093\/brain\/awx242","article-title":"Upper limb cortical maps in amputees with targeted muscle and sensory reinnervation","volume":"140","author":"Serino","year":"2017","journal-title":"Brain J. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"421e","DOI":"10.1097\/PRS.0000000000005922","article-title":"Prophylactic Regenerative Peripheral Nerve Interfaces to Prevent Postamputation Pain","volume":"144","author":"Kubiak","year":"2019","journal-title":"Plast. Reconstr. Surg."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/2\/417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:26:31Z","timestamp":1759919191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/2\/417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,10]]},"references-count":31,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["jcm14020417"],"URL":"https:\/\/doi.org\/10.3390\/jcm14020417","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,10]]}}}