Locus coeruleus tonic upregulation increases selectivity to inconspicuous auditory information in autistic compared to non-autistic individuals: a combined pupillometry and electroencephalography study / Nico BAST in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 41 Titre : Locus coeruleus tonic upregulation increases selectivity to inconspicuous auditory information in autistic compared to non-autistic individuals: a combined pupillometry and electroencephalography study Type de document : texte imprimé Auteurs : Nico BAST, Auteur ; Jumana AHMAD, Auteur ; Luke MASON, Auteur ; Emily J H JONES, Auteur ; Magdalena MATYJEK, Auteur ; Leonie POLZER, Auteur ; Christina LUCKHARDT, Auteur ; Anna Katharina MÃœLLER, Auteur ; Grainne M MCALONAN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Sarah BAUMEISTER, Auteur ; Eva LOTH, Auteur ; Christine M. FREITAG, Auteur ; Nico Secondary BAST, Auteur ; Jumana AHMAD, Auteur ; Luke MASON, Auteur ; Emily J H JONES, Auteur ; Magdalena MATYJEK, Auteur ; Leonie POLZER, Auteur ; Christina LUCKHARDT, Auteur ; Anna Katharina MÃœLLER, Auteur ; Grainne M MCALONAN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Sarah BAUMEISTER, Auteur ; Eva LOTH, Auteur ; Christine M. FREITAG, Auteur Article en page(s) : 41 Langues : Anglais (eng) Mots-clés : Humans  Male  Electroencephalography/methods  Female  Autistic Disorder/physiopathology  Adult  Locus Coeruleus/physiopathology/metabolism  Young Adult  Pupil/physiology  Auditory Perception  Adolescent  Acoustic Stimulation  Up-Regulation  Case-Control Studies  Arousal  Auditory oddball paradigm  Autism spectrum condition  Mismatch negativity  Predictive coding  Pupillometry  (where appropriate) and their parent/legal guardian provided written informed  consent. Ethical approval for this study was obtained through ethics committees  at each site (King’s College London—London Queen Square Health Research Authority  Research Ethics Committee: 13/LO/1156  Autism Research Centre, University of  Cambridge—London Queen Square Health Research Authority Research Ethics  Committee: 13/LO/1156  Radboud University Medical Centre—Quality and Safety  Committee on Research Involving Human Subjects Arnhem-Nijmegen: 2013/455,  University Medical Centre Utrecht—- Quality and Safety Committee on Research  Involving Human Subjects Arnhem-Nijmegen: 2013/455  Central Insitute of Mental  Health—University Medical Mannheim, Medical Ethics Commission II: 2014-540N-MA  Universita Campus Bio-Medica De Roma—Medical Ethics Committee: 18/14 PAR ComET  CBM  Karolinska Intitute – Central Ethical Review Board: 32–2010). Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing. METHODS: Autistic (n = 139) and non-autistic (n = 98) individuals were assessed during a passive auditory oddball task with pupillometry and electroencephalography. For every trial, a baseline pupil size (BPS) assessed LC-NE tonic activity that coincides with current arousal, while a stimulus-evoked pupillary response (SEPR) assessed LC-NE phasic activity that estimated sensory selectivity. Electroencephalography assessed amplitudes of mismatch negativity (MMN-amp) that estimated pre-attentive change detection as a brain-activity readout of sensory selectivity. Measures were modeled between groups within the task by combining Frequentist and Bayesian approaches. RESULTS: Across groups, higher BPS was associated with more negative MMN-amp to standards and oddballs. A more negative MMN-amp to standards was associated with a higher SEPR to standards. Controlling for these associations, autistic versus non-autistic individuals showed a higher SEPR in response to standards. In addition, a positive association of BPS and SEPR to standards was specific to autistic individuals. With task progression, autistic versus non-autistic individuals showed a higher initial increase and subsequently steeper decrease of BPS. This was supported by Bayesian posterior distribution estimates. LIMITATIONS: A short trial duration required concatenating trials to epochs and applying a linear-time invariant filter to capture the slow pupil changes. Without an LC-NE manipulation, we cannot rule out that pupil changes are evoked by other cortical pathways than the LC-NE. CONCLUSIONS: Across groups, LC-NE tonic upregulation is emphasized as a general mechanism that un-specifically increases pre-attentive change detection to all sensory stimuli, which then increases sensory selectivity to frequent stimuli. In autistic individuals, different sensory processing is characterized by increased sensory selectivity to frequent stimuli. This is likely caused by an LC-NE tonic upregulation. It associates autistic sensory processing with increased arousal upregulation that increases sensory selectivity to inconspicuous auditory information. En ligne : https://dx.doi.org/10.1186/s13229-025-00678-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569 [article] Locus coeruleus tonic upregulation increases selectivity to inconspicuous auditory information in autistic compared to non-autistic individuals: a combined pupillometry and electroencephalography study [texte imprimé] / Nico BAST, Auteur ; Jumana AHMAD, Auteur ; Luke MASON, Auteur ; Emily J H JONES, Auteur ; Magdalena MATYJEK, Auteur ; Leonie POLZER, Auteur ; Christina LUCKHARDT, Auteur ; Anna Katharina MÃœLLER, Auteur ; Grainne M MCALONAN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Sarah BAUMEISTER, Auteur ; Eva LOTH, Auteur ; Christine M. FREITAG, Auteur ; Nico Secondary BAST, Auteur ; Jumana AHMAD, Auteur ; Luke MASON, Auteur ; Emily J H JONES, Auteur ; Magdalena MATYJEK, Auteur ; Leonie POLZER, Auteur ; Christina LUCKHARDT, Auteur ; Anna Katharina MÃœLLER, Auteur ; Grainne M MCALONAN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Sarah BAUMEISTER, Auteur ; Eva LOTH, Auteur ; Christine M. FREITAG, Auteur . - 41. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 41 Mots-clés : Humans  Male  Electroencephalography/methods  Female  Autistic Disorder/physiopathology  Adult  Locus Coeruleus/physiopathology/metabolism  Young Adult  Pupil/physiology  Auditory Perception  Adolescent  Acoustic Stimulation  Up-Regulation  Case-Control Studies  Arousal  Auditory oddball paradigm  Autism spectrum condition  Mismatch negativity  Predictive coding  Pupillometry  (where appropriate) and their parent/legal guardian provided written informed  consent. Ethical approval for this study was obtained through ethics committees  at each site (King’s College London—London Queen Square Health Research Authority  Research Ethics Committee: 13/LO/1156  Autism Research Centre, University of  Cambridge—London Queen Square Health Research Authority Research Ethics  Committee: 13/LO/1156  Radboud University Medical Centre—Quality and Safety  Committee on Research Involving Human Subjects Arnhem-Nijmegen: 2013/455,  University Medical Centre Utrecht—- Quality and Safety Committee on Research  Involving Human Subjects Arnhem-Nijmegen: 2013/455  Central Insitute of Mental  Health—University Medical Mannheim, Medical Ethics Commission II: 2014-540N-MA  Universita Campus Bio-Medica De Roma—Medical Ethics Committee: 18/14 PAR ComET  CBM  Karolinska Intitute – Central Ethical Review Board: 32–2010). Consent for  publication: Not applicable. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Sensory processing requires selectivity to salient sensory input. Many autistic individuals report different sensory processing, which has been associated with altered sensory selectivity. The locus-coeruleus norepinephrine (LC-NE) system modulates the neuronal gain of sensory input, which represents a neurophysiological mechanism of sensory selectivity. In autistic individuals, we hypothesized that LC-NE tonic upregulation reduces sensory selectivity and underlies different sensory processing. METHODS: Autistic (n = 139) and non-autistic (n = 98) individuals were assessed during a passive auditory oddball task with pupillometry and electroencephalography. For every trial, a baseline pupil size (BPS) assessed LC-NE tonic activity that coincides with current arousal, while a stimulus-evoked pupillary response (SEPR) assessed LC-NE phasic activity that estimated sensory selectivity. Electroencephalography assessed amplitudes of mismatch negativity (MMN-amp) that estimated pre-attentive change detection as a brain-activity readout of sensory selectivity. Measures were modeled between groups within the task by combining Frequentist and Bayesian approaches. RESULTS: Across groups, higher BPS was associated with more negative MMN-amp to standards and oddballs. A more negative MMN-amp to standards was associated with a higher SEPR to standards. Controlling for these associations, autistic versus non-autistic individuals showed a higher SEPR in response to standards. In addition, a positive association of BPS and SEPR to standards was specific to autistic individuals. With task progression, autistic versus non-autistic individuals showed a higher initial increase and subsequently steeper decrease of BPS. This was supported by Bayesian posterior distribution estimates. LIMITATIONS: A short trial duration required concatenating trials to epochs and applying a linear-time invariant filter to capture the slow pupil changes. Without an LC-NE manipulation, we cannot rule out that pupil changes are evoked by other cortical pathways than the LC-NE. CONCLUSIONS: Across groups, LC-NE tonic upregulation is emphasized as a general mechanism that un-specifically increases pre-attentive change detection to all sensory stimuli, which then increases sensory selectivity to frequent stimuli. In autistic individuals, different sensory processing is characterized by increased sensory selectivity to frequent stimuli. This is likely caused by an LC-NE tonic upregulation. It associates autistic sensory processing with increased arousal upregulation that increases sensory selectivity to inconspicuous auditory information. En ligne : https://dx.doi.org/10.1186/s13229-025-00678-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=569

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