ArticleProceedings of the National Academy of Sciences of the United States of America2020
Deep learning of spontaneous arousal fluctuations detects early cholinergic defects across neurodevelopmental mouse models and patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Targeting the cholinergic and endocannabinoid systems as a therapeutic intervention for core and associated phenotypes in the autism model; a systematic review.Trends in psychiatry and psychotherapy · 2025Pooled it
- MEYELens: An affordable, open-source, 3D-printable eyewear platform for pupillometry and gaze tracking.Behavior research methods · 2026Article
- The Pupil-Brain System at Rest: Spontaneous Pupil Fluctuations as Markers of Neuromodulatory and Network Dynamics.Psychophysiology · 2026Review
- Temporal variability in pupillary asymmetry reflects ADHD-related traits in preschool and early school-aged children.Frontiers in cognition · 2026Article
- Independent genetic strategies define the scope and limits of CDKL5 deficiency disorder reversal.Cell reports. Medicine · 2025Article
- Transfer Learning in Cancer Genetics, Mutation Detection, Gene Expression Analysis, and Syndrome Recognition.Cancers · 2024Review
- Cell type-specific expression, regulation and compensation of CDKL5 activity in mouse brain.Molecular psychiatry · 2024Article
- Sound elicits stereotyped facial movements that provide a sensitive index of hearing abilities in mice.Current biology : CB · 2024Article
- New eye tracking metrics system: the value in early diagnosis of autism spectrum disorder.Frontiers in psychiatry · 2024Article
- Recent trends in multiple metrics and multimodal analysis for neural activity and pupillometry.Frontiers in neurology · 2024Article
- Natural language processing and expert follow-up establishes tachycardia association with CDKL5 deficiency disorder.Genetics in medicine open · 2024Article
- Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability.Nature communications · 2023Article
- Article
- Altered pupil responses to social and non-social stimuli in Shank3 mutant dogs.Molecular psychiatry · 2023Article
- Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling.Molecular autism · 2023Article
- Mecp2 deletion results in profound alterations of developmental and adult functional connectivity.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Genomic, transcriptomic, and epigenomic analysis of a medicinal snake,Acta pharmaceutica Sinica. B · 2023Article
- The Impact of Artificial Intelligence in the Odyssey of Rare Diseases.Biomedicines · 2023Review
- From pupil to the brain: New insights for studying cortical plasticity through pupillometry.Frontiers in neural circuits · 2023Review
- Identification of diagnostic markers for ASD: a restrictive interest analysis based on EEG combined with eye tracking.Frontiers in neuroscience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Neurodevelopmental spectrum disorders like autism (ASD) are diagnosed, on average, beyond age 4 y, after multiple critical periods of brain development close and behavioral intervention becomes less effective. This raises the urgent need for quantitative, noninvasive, and translational biomarkers for their early detection and tracking. We found that both idiopathic (BTBR) and genetic (CDKL5- and MeCP2-deficient) mouse models of ASD display an early, impaired cholinergic neuromodulation as reflected in altered spontaneous pupil fluctuations. Abnormalities were already present before the onset of symptoms and were rescued by the selective expression of MeCP2 in cholinergic circuits. Hence, we trained a neural network (ConvNetACh) to recognize, with 97% accuracy, patterns of these arousal fluctuations in mice with enhanced cholinergic sensitivity (LYNX1-deficient). ConvNetACh then successfully detected impairments in all ASD mouse models tested except in MeCP2-rescued mice. By retraining only the last layers of ConvNetACh with heart rate variation data (a similar proxy of arousal) directly from Rett syndrome patients, we generated ConvNetPatients, a neural network capable of distinguishing them from typically developing subjects. Even with small cohorts of rare patients, our approach exhibited significant accuracy before (80% in the first and second year of life) and into regression (88% in stage III patients). Thus, transfer learning across species and modalities establishes spontaneous arousal fluctuations combined with deep learning as a robust noninvasive, quantitative, and sensitive translational biomarker for the rapid and early detection of neurodevelopmental disorders before major symptom onset.
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