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The locus coeruleus-norepinephrine (LC-NE) system modulates sensory processing by increasing selectivity to salience. To specify this mechanism, we manipulated LC-NE activity and explored sensory selectivity in autistic and non-autistic adolescents. We assessed pupillometry and electroencephalography (EEG) in 52 autistic adolescents (ASD), 55 healthy controls (CON), and 43 adolescents with other mental health conditions (MHC) during a passive auditory oddball task. A handgrip exercise manipulated LC-NE activity. Baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR) measured LC-NE tonic and phasic activity, respectively. Sensory selectivity was estimated with mismatch negativity (MMN) as change detection and P3a as bottom-up attention. Oddballs versus standards elicited increased SEPR, MMN amplitude, and longer MMN and P3a latencies. Increased P3a amplitude was more consistent in ASD. Across oddballs and standards, the manipulation transiently increased MMN and P3a amplitudes. A manipulation-induced BPS increase was specific to ASD and MHC. Pupillometric measures (BPS, SEPR) modulated sensory selectivity measures (MMN, P3a) differently between clinical groups (ASD, MHC) and CON. Findings indicate an altered orienting response to sensory stimuli in autism. The manipulation did not increase sensory selectivity but temporarily enhanced sensory reactivity to all stimuli with an arousal upregulation in both clinical groups. LC-NE activity was differentially related to sensory selectivity in autism and other mental health conditions. The tonic upregulation is discussed as increased stress susceptibility across autism and other mental health conditions.<\/jats:p>","DOI":"10.1038\/s41398-026-03948-0","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:08:42Z","timestamp":1774325322000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Locus coeruleus modulation of neurophysiological sensory selectivity differs in autism and other mental health conditions"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2176-0861","authenticated-orcid":false,"given":"Anna K.","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5259-7174","authenticated-orcid":false,"given":"Christina","family":"Luckhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-4782","authenticated-orcid":false,"given":"Christine M.","family":"Freitag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5721-207X","authenticated-orcid":false,"given":"Nico","family":"Bast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"3948_CR1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. 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She has served as consultant for the German Institute for Quality and Efficiency in Health Care (Institut f\u00fcr Qualit\u00e4t und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) and the companies IGES and Infectopharm during the last 3 years. She has received research funding by the German Research Foundation (DFG), the German Ministry of Science and Education and the European Commission. NB receives royalties for lecturing at institutes for training in psychotherapy and receives third-party funding by the German Research Foundation (DFG), the Daimler and Benz Foundation, and the Johanna Quandt Young Academy. CL received funding by the German Research Foundation (DFG). AKM has declared that she has no competing or potential conflicts of interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The experiment was performed in accordance with the Declaration of Helsinki. 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