{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:54:59Z","timestamp":1791024899337,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Rehabilitation Medicine and Physical Therapy","reference-count":24,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R35 NS122336-01"],"award-info":[{"award-number":["R35 NS122336-01"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Corticospinal\u2013motoneuronal connections are more prominent in distal than proximal upper-limb muscles, but whether this anatomical specialization influences the capacity for activity-dependent plasticity remains unknown. Here, we tested whether Hebbian stimulation targeting corticospinal\u2013motoneuronal connections, induces muscle-specific plasticity in proximal and distal arm muscles in healthy humans. We applied a spike-timing-dependent stimulation protocol comprising 180 paired stimuli, with transcranial magnetic stimulation timed to evoke corticospinal volleys 1\u20132 ms before motoneurons were antidromically activated by electrical stimulation of the brachial plexus for the biceps brachii or the ulnar nerve for the first dorsal interosseous (FDI). Corticospinal excitability was assessed by measuring motor-evoked potentials (MEPs) before and 30 min after stimulation. Hebbian stimulation increased MEP amplitudes in both muscles, but facilitation was greater in the FDI than in the biceps. Because resting motor threshold was higher for the biceps than for the FDI, in a control experiment we matched stimulation intensities between muscles. Under these conditions, Hebbian stimulation continued producing greater facilitation in the FDI than in the biceps, indicating that the difference was not attributable to stimulation intensity. Moreover, changes in MEP amplitude were associated with maximal MEP size in the FDI but not in the biceps, whereas no muscle-specific association was observed with peripheral responses (M-max), supporting a stronger relationship between corticospinal drive and Hebbian plasticity in the distal than in the proximal arm muscle. Together, these findings identify a distal-to-proximal gradient in Hebbian plasticity across arm muscles, which may contribute to optimizing targeted neuromodulation approaches for upper-limb rehabilitation.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Plasticity in distal and proximal upper-limb muscles remains poorly understood<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Ability to induce Hebbian plasticity was greater in a hand than in proximal arm muscle<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>A distal-to-proximal gradient in Hebbian plasticity may inform targeted rehabilitation<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.23.26363732","type":"posted-content","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:45:10Z","timestamp":1790725510000},"source":"Crossref","is-referenced-by-count":0,"title":["A Distal\u2013Proximal Gradient of Hebbian Plasticity in the Human Arm"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8770-585X","authenticated-orcid":false,"given":"Minkyu","family":"Lee","sequence":"first","affiliation":[{"name":"Shirley Ryan AbilityLab, Chicago, IL, USA"},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T.","family":"Farley","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Chicago, IL, USA"},{"name":"Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Chen","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Chicago, IL, USA"},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA"},{"name":"Edward Hines Jr. VA Hospital, Hines, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Sangari","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Chicago, IL, USA"},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica A.","family":"Perez","sequence":"additional","affiliation":[{"name":"Shirley Ryan AbilityLab, Chicago, IL, USA"},{"name":"Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA"},{"name":"Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, IL, USA"},{"name":"Edward Hines Jr. VA Hospital, Hines, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100303301310000_2026.09.23.26363732v1.1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.31.060407.125547"},{"key":"2026100303301310000_2026.09.23.26363732v1.2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808362106"},{"key":"2026100303301310000_2026.09.23.26363732v1.3","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019048"},{"key":"2026100303301310000_2026.09.23.26363732v1.4","doi-asserted-by":"crossref","unstructured":"Koponen LM , Martinez M , Wood E , Murphy DLK , Goetz SM , Appelbaum LG , Peterchev AV . Transcranial magnetic stimulation input-output curve slope differences suggest variation in recruitment across muscle representations in primary motor cortex. 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