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U.S.A."],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:p>In congenital handlessness, where individuals rely on their feet for compensatory manual functions, reorganization in the primary somatosensory cortex (SI) appears to be limited to local shifts by adjacent body parts. It remains unclear how congenital handlessness and lifelong compensatory foot use shape the sensorimotor system beyond SI, and whether compensatory abilities can drive broader functional reorganization. Here, we used task-based and resting-state functional MRI (fMRI) to investigate how compensatory foot use changes body representations in the secondary somatosensory cortex (SII) in people born without hands (individuals with upper-limb dysplasia, IDs). We found that IDs showed a shift toward foot selectivity in the left hand-selective SII, with stronger foot activity than typically developed (TD) control participants during action execution. Notably, this reorganization in the left SII hand area cannot simply be explained by this area\u2019s intrinsic organization\u2014the typical secondary preference of this area in the TDs when hand responses are excluded: TDs showed both shoulder and foot selectivity when the hand activity was excluded from the analysis in this area, whereas the reorganization in IDs was limited to the foot. This indicates a functional reweighting that stems from the IDs\u2019 sensorimotor experience. Resting-state results further revealed altered functional connectivity between SII and primary sensorimotor regions in IDs. Our findings suggest that SII exhibits flexible, experience-dependent plasticity, revealing a hierarchical principle of cortical plasticity, whereby reorganization in the SI is constrained by somatotopic principles while SII reflects functional or experience-dependent reweighting plasticity.<\/jats:p>","DOI":"10.1073\/pnas.2602353123","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:12:05Z","timestamp":1790017925000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Experience-driven plasticity in the secondary somatosensory cortex in people born without hands"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-0796","authenticated-orcid":false,"given":"Zhiqing","family":"Deng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hjz7x27","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Georgetown University Medical Center","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5334-6772","authenticated-orcid":false,"given":"Florencia","family":"Martinez-Addiego","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hjz7x27","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Georgetown University Medical Center","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hjz7x27","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Georgetown University Medical Center","place":["Washington"]},{"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"publisher"}],"name":"Global Institute of Future Technology, Shanghai Jiao Tong University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-3455","authenticated-orcid":false,"given":"Ella","family":"Striem-Amit","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00hjz7x27","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neuroscience, Georgetown University Medical Center","place":["Washington"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/60.4.389"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ps.38.020187.001021"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-003-1794-9"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.03.053"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1803926115"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.84716"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02037-7"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902240408"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/375482a0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2006.03.005"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-003-1591-5"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2017789117"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2503188122"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2025.121124"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1058-11.2011"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00312.2014"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5242-13.2014"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.02.029"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1162\/jocn_a_02102"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","unstructured":"L. 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