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Record W4413397318 · doi:10.1186/s13229-025-00678-w

Locus coeruleus tonic upregulation increases selectivity to inconspicuous auditory information in autistic compared to non-autistic individuals: a combined pupillometry and electroencephalography study

2025· article· en· W4413397318 on OpenAlexaff
Nico Bast, Jumana Ahmad, Luke Mason, Emily J. H. Jones, Magdalena Matyjek, Leonie Polzer, Christina Luckhardt, Anna K Müller, Gráinne McAlonan, Tobias Banaschewski, Sarah Baumeister, Eva Loth, Christine M. Freitag, Sara Ambrosino, Bonnie Auyeung, Simon Baron‐Cohen, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Carsten Bours, Michael J. Brammer, Daniel Brandeis, Claudia Brogna, Yvette de Bruijn, Jan K. Buitelaar, Bhismadev Chakrabarti, Tony Charman, Ineke Cornelissen, Daisy Crawley, Flavio Dell’Acqua, Guillaume Dumas, Sarah Durston, Christine Ecker, Jessica Faulkner, Vincent Frouin, Pilar Garcés, David Goyard, Lindsay Ham, Hannah Hayward, Joerg F. Hipp, Rosemary Holt, Mark Johnson, Prantik Kundu, Meng‐Chuan Lai, Xavier Liogier D’ardhuy, Michael Lombardo, David J. Lythgoe, René C.W. Mandl, André F. Marquand, Maarten Mennes, Andreas Meyer‐Lindenberg, Carolin Moessnang, Declan Murphy, Bethany Oakley, Laurence O’Dwyer, Marianne Oldehinkel, Bob Oranje, Gahan Pandina, Antonio M. Persico, Barbara Ruggeri, Amber Ruigrok, Jessica Sabet, Roberto Sacco, Antonia San José Cáceres, Emily Simonoff, Will Spooren, Julian Tillmann, Roberto Toro, Heike Tost, Jack Waldman, Steven Williams, Caroline Wooldridge, Marcel P. Zwiers

Bibliographic record

VenueMolecular Autism · 2025
Typearticle
Languageen
FieldNeuroscience
TopicNeural and Behavioral Psychology Studies
Canadian institutionsCentre for Addiction and Mental Health
FundersSeventh Framework ProgrammeHORIZON EUROPE Framework Programme
KeywordsPupillometryElectroencephalographyLocus coeruleusPsychologyNeuropsychologyAutistic traitsAudiologyAutismNeuroscienceCognitive psychologyMedicineDevelopmental psychologyCognitionPupilAutism spectrum disorder

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.648
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.018
GPT teacher head0.316
Teacher spread0.298 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations4
Published2025
Admission routes1
Has abstractyes

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