{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:59:08Z","timestamp":1785178748781,"version":"3.55.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Variability in poststroke language outcomes remains insufficiently explained by established clinical system neuroscience concepts. This study examined whether damage to neurotransmitter-informed structural networks is associated with poststroke language impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Two openly available cohorts of patients with left-hemispheric stroke were analyzed: the Washington Stroke Cohort (St. Louis), including patients after a first symptomatic stroke (acute phase), and the Aphasia Recovery Cohort (South Carolina), focusing on chronic recovery. Language performance was assessed cross-sectionally using either a comprehensive language battery (Washington Stroke Cohort; 1\u20132 weeks poststroke) or the Western Aphasia Battery-Revised (Aphasia Recovery Cohort; chronic stage). Individual stroke lesion masks were embedded into normative connectomes weighted by positron-emission tomography\u2013derived density maps of 16 neurotransmitter receptors\/transporters. Partial least squares regression and adjusted linear regressions (age, sex, lesion volume, and time poststroke) identified predictors of language functioning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Two hundred seventy patients were included. Washington Stroke Cohort (n=44): mean age, 54.2\u00b112.3 years; 45.5% female; median, 12 days poststroke (interquartile range, 10\u201314). Aphasia Recovery Cohort (n=226): mean age, 57.8\u00b111.2 years; 38.4% female; and median, 721 days poststroke (interquartile range, 403\u20131765). Across both cohorts, partial least squares analyses converged on a neurochemical profile in which damage to networks related to serotonergic (5-HT\n                      <jats:sub>1a<\/jats:sub>\n                      and 5-HT\n                      <jats:sub>2a<\/jats:sub>\n                      ) and dopaminergic (D1) receptor distributions showed the strongest associations with poorer language performance. Damage to 5-HT\n                      <jats:sub>1a<\/jats:sub>\n                      and D1 networks remained significant in fully adjusted models, improving fit over covariate-only models (all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      &lt;0.001; Washington Stroke Cohort: \u2206AIC\n                      <jats:sub>5-HT1a<\/jats:sub>\n                      =1.77 and \u2206AIC\n                      <jats:sub>D1<\/jats:sub>\n                      =0.96; Aphasia Recovery Cohort: \u2206AIC\n                      <jats:sub>5-HT1a<\/jats:sub>\n                      =25.29 and \u2206AIC\n                      <jats:sub>D1<\/jats:sub>\n                      =19.96).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      The disruption of large-scale serotonergic (5-HT\n                      <jats:sub>1a<\/jats:sub>\n                      ) and dopaminergic (D1) networks is associated with language impairment in acute to subacute and chronic stroke. Neurotransmitter-related network damage, based on normative positron-emission tomography\u2013derived maps serving as a structural proxy of neurotransmitter systems, explained additional variability beyond clinical variables and lesion burden, providing a neurochemically informed network framework for understanding variability in poststroke aphasia. However, given the indirect nature of the measures, implications for clinical translation and targeted rehabilitation strategies remain preliminary.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.126.055890","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:00:24Z","timestamp":1781254824000},"page":"2482-2492","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Neurotransmitter-Informed Connectome Approach to Language Impairment After Stroke"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9044-8224","authenticated-orcid":true,"given":"Tom","family":"Hornberger","sequence":"first","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0913-899X","authenticated-orcid":true,"given":"Robert","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8795-758X","authenticated-orcid":true,"given":"Philipp J.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Neurology, Charit\u00e9 Berlin, Germany (P.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan F.","family":"Feldheim","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6047-3623","authenticated-orcid":true,"given":"Pawe\u0142 P.","family":"Wr\u00f3bel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-1449","authenticated-orcid":true,"given":"G\u00f6tz","family":"Thomalla","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Magnus","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1808-0913","authenticated-orcid":true,"given":"Dorothee","family":"Saur","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Leipzig Medical Center, Germany (D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7042-6785","authenticated-orcid":true,"given":"Fanny","family":"Quandt","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-0801","authenticated-orcid":true,"given":"Benedikt M.","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Hamburg-Eppendorf, Germany (T.H., R.S., J.F.F., P.P.W., G.T., T.M., F.Q., B.M.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2016.03.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2020.1855976"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1080\/02687038.2020.1727838"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.120.031162"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1044\/2018_AJSLP-18-0123"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25184"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07607-9"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4396-15.2016"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf185"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57680-2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","unstructured":"Daoran W Dongdong J Zhang T. 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