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Autism spectrum disorder detection using variable frequency complex demodulation of the electroretinogram / Sultan Mohammad MANJUR ; Md Billal HOSSAIN ; Fernando MARMOLEJO-RAMOS ; Irene O. LEE ; David H. SKUSE ; Dorothy A. THOMPSON ; Paul A. CONSTABLE in Research in Autism Spectrum Disorders, 109 (November 2023)
[article]
Titre : Autism spectrum disorder detection using variable frequency complex demodulation of the electroretinogram Type de document : Texte imprimé et/ou numérique Auteurs : Sultan Mohammad MANJUR, Auteur ; Md Billal HOSSAIN, Auteur ; Fernando MARMOLEJO-RAMOS, Auteur ; Irene O. LEE, Auteur ; David H. SKUSE, Auteur ; Dorothy A. THOMPSON, Auteur ; Paul A. CONSTABLE, Auteur Article en page(s) : 102258 Langues : Anglais (eng) Mots-clés : Electroretinogram Signal analysis Autism spectrum disorder Machine learning Index. décimale : PER Périodiques Résumé : The early diagnosis of neurodevelopmental conditions such as autism spectrum disorder (ASD), is an unmet need. One difficulty is the identification of a biological signal that relates to the ASD phenotype. The electroretinogram (ERG) waveform has been identified as a possible signal that could categorize neurological conditions such as ASD. The ERG waveform is derived from the electrical activity of photoreceptors and retinal neurons in response to a brief flash of light and provides an indirect 'window' into the central nervous system. Traditionally, the waveform is analyzed in the time-domain, but more recently time-frequency spectrum (TFS) analysis of ERG has been successfully carried out using discrete wavelet transformation (DWT) to characterize the morphological features of the signal. In this study, we propose the use of a high resolution TFS technique, namely variable frequency complex demodulation (VFCDM), to decompose the ERG waveform based on two signal flash strengths to build machine learning (ML) models to categorize ASD. ERG waveforms from N = 217 subjects (71 ASD, 146 control), at two different flash strengths, 446 and 113 Troland seconds (Td.s), from both right and left eyes were included. We analyzed the raw ERG waveforms using DWT and VFCDM. We computed features from the TFSs and trained ML models such as Random Forest, Gradient Boosting, Support Vector Machine to classify ASD from controls. ML models were validated using a subject independent validation strategy, and we found that the ML models with VFCDM features outperformed models using the DWT, achieving an area under the receiver operating characteristics curve of 0.90 (accuracy = 0.81, sensitivity = 0.85, specificity = 0.78). We found that the higher frequency range (80-300 Hz) included more relevant information for classifying ASD compared to the lower frequencies. We also found that the stronger flash strength of 446 Td.s in the right eye provided the best classification result which supports VFCDM analysis of the ERG waveform as a potential tool to aid in the identification of the ASD phenotype. En ligne : https://doi.org/10.1016/j.rasd.2023.102258 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=517
in Research in Autism Spectrum Disorders > 109 (November 2023) . - 102258[article] Autism spectrum disorder detection using variable frequency complex demodulation of the electroretinogram [Texte imprimé et/ou numérique] / Sultan Mohammad MANJUR, Auteur ; Md Billal HOSSAIN, Auteur ; Fernando MARMOLEJO-RAMOS, Auteur ; Irene O. LEE, Auteur ; David H. SKUSE, Auteur ; Dorothy A. THOMPSON, Auteur ; Paul A. CONSTABLE, Auteur . - 102258.
Langues : Anglais (eng)
in Research in Autism Spectrum Disorders > 109 (November 2023) . - 102258
Mots-clés : Electroretinogram Signal analysis Autism spectrum disorder Machine learning Index. décimale : PER Périodiques Résumé : The early diagnosis of neurodevelopmental conditions such as autism spectrum disorder (ASD), is an unmet need. One difficulty is the identification of a biological signal that relates to the ASD phenotype. The electroretinogram (ERG) waveform has been identified as a possible signal that could categorize neurological conditions such as ASD. The ERG waveform is derived from the electrical activity of photoreceptors and retinal neurons in response to a brief flash of light and provides an indirect 'window' into the central nervous system. Traditionally, the waveform is analyzed in the time-domain, but more recently time-frequency spectrum (TFS) analysis of ERG has been successfully carried out using discrete wavelet transformation (DWT) to characterize the morphological features of the signal. In this study, we propose the use of a high resolution TFS technique, namely variable frequency complex demodulation (VFCDM), to decompose the ERG waveform based on two signal flash strengths to build machine learning (ML) models to categorize ASD. ERG waveforms from N = 217 subjects (71 ASD, 146 control), at two different flash strengths, 446 and 113 Troland seconds (Td.s), from both right and left eyes were included. We analyzed the raw ERG waveforms using DWT and VFCDM. We computed features from the TFSs and trained ML models such as Random Forest, Gradient Boosting, Support Vector Machine to classify ASD from controls. ML models were validated using a subject independent validation strategy, and we found that the ML models with VFCDM features outperformed models using the DWT, achieving an area under the receiver operating characteristics curve of 0.90 (accuracy = 0.81, sensitivity = 0.85, specificity = 0.78). We found that the higher frequency range (80-300 Hz) included more relevant information for classifying ASD compared to the lower frequencies. We also found that the stronger flash strength of 446 Td.s in the right eye provided the best classification result which supports VFCDM analysis of the ERG waveform as a potential tool to aid in the identification of the ASD phenotype. En ligne : https://doi.org/10.1016/j.rasd.2023.102258 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=517 Light-Adapted Electroretinogram Differences in Autism Spectrum Disorder / Paul A. CONSTABLE in Journal of Autism and Developmental Disorders, 50-8 (August 2020)
[article]
Titre : Light-Adapted Electroretinogram Differences in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Paul A. CONSTABLE, Auteur ; Edward R. RITVO, Auteur ; Ariella R. RITVO, Auteur ; Irene O. LEE, Auteur ; Morgan L. MCNAIR, Auteur ; Dylan STAHL, Auteur ; Jane SOWDEN, Auteur ; Stephen QUINN, Auteur ; David H. SKUSE, Auteur ; Dorothy A. THOMPSON, Auteur ; James C. MCPARTLAND, Auteur Article en page(s) : p.2874-2885 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Electroretinogram b-wave Index. décimale : PER Périodiques Résumé : Light-adapted (LA) electroretinograms (ERGs) from 90 individuals with autism spectrum disorder (ASD), mean age (13.0?±?4.2), were compared to 87 control subjects, mean age (13.8?±?4.8). LA-ERGs were produced by a random series of nine different Troland based, full-field flash strengths and the ISCEV standard flash at 2/s on a 30 cd m(-2) white background. A random effects mixed model analysis showed the ASD group had smaller b- and a-wave amplitudes at high flash strengths (p?.001) and slower b-wave peak times (p?.001). Photopic hill models showed the peaks of the component Gaussian (p?=?.035) and logistic functions (p?=?.014) differed significantly between groups. Retinal neurophysiology assessed by LA-ERG provides insight into neural development in ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04396-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=428
in Journal of Autism and Developmental Disorders > 50-8 (August 2020) . - p.2874-2885[article] Light-Adapted Electroretinogram Differences in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Paul A. CONSTABLE, Auteur ; Edward R. RITVO, Auteur ; Ariella R. RITVO, Auteur ; Irene O. LEE, Auteur ; Morgan L. MCNAIR, Auteur ; Dylan STAHL, Auteur ; Jane SOWDEN, Auteur ; Stephen QUINN, Auteur ; David H. SKUSE, Auteur ; Dorothy A. THOMPSON, Auteur ; James C. MCPARTLAND, Auteur . - p.2874-2885.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 50-8 (August 2020) . - p.2874-2885
Mots-clés : Autism spectrum disorder Electroretinogram b-wave Index. décimale : PER Périodiques Résumé : Light-adapted (LA) electroretinograms (ERGs) from 90 individuals with autism spectrum disorder (ASD), mean age (13.0?±?4.2), were compared to 87 control subjects, mean age (13.8?±?4.8). LA-ERGs were produced by a random series of nine different Troland based, full-field flash strengths and the ISCEV standard flash at 2/s on a 30 cd m(-2) white background. A random effects mixed model analysis showed the ASD group had smaller b- and a-wave amplitudes at high flash strengths (p?.001) and slower b-wave peak times (p?.001). Photopic hill models showed the peaks of the component Gaussian (p?=?.035) and logistic functions (p?=?.014) differed significantly between groups. Retinal neurophysiology assessed by LA-ERG provides insight into neural development in ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04396-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=428 Electroretinography in adults with high-functioning autism spectrum disorder / Evelyn B. N. FRIEDEL in Autism Research, 15-11 (November 2022)
[article]
Titre : Electroretinography in adults with high-functioning autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Evelyn B. N. FRIEDEL, Auteur ; Mirjam SCHAFER, Auteur ; Dominique ENDRES, Auteur ; Simon MAIER, Auteur ; Kimon RUNGE, Auteur ; Michael BACH, Auteur ; Sven P. HEINRICH, Auteur ; Dieter EBERT, Auteur ; Katharina DOMSCHKE, Auteur ; Ludger TEBARTZ VAN ELST, Auteur ; Kathrin NICKEL, Auteur Article en page(s) : p.2026-2037 Langues : Anglais (eng) Mots-clés : Adult Humans Electroretinography/methods Retinal Ganglion Cells/physiology Autism Spectrum Disorder Photic Stimulation Retina/physiology Asd Erg PhNR a-wave autism spectrum disorder b-wave electroretinogram photopic negative response Index. décimale : PER Périodiques Résumé : The electroretinogram (ERG) allows the investigation of retinal signaling pathways and has increasingly been applied in individuals with mental disorders in search for potential biomarkers of neurodevelopmental disorders. Preceding ERG examinations in individuals with autism spectrum disorders (ASD) showed inconsistent results, which might be due to the small number of participants, heterogeneity of the ASD population, differences in age ranges, and stimulation methods. The aim of this study was to investigate functional retinal responses in adults with ASD by means of the light-adapted (photopic) ERG. Light-adapted ERG measurements were obtained with the RETeval® system applying three different stimulation protocols. In the final analysis, the ERG parameters a-wave, b-wave, the photopic negative response (PhNR), the photopic hill parameters as well as additional amplitude ratios were compared between 32 adults with high-functioning ASD and 31 non-autistic controls. Both groups were matched with regard to sex and age. No significant functional retinal differences in amplitude or peak time of the a- or b-wave, PhNR, the photopic hill parameters or the ERG-amplitude ratios could be detected in individuals with ASD compared to non-autistic participants. The absence of electrophysiological functional retinal alterations in ASD, suggests that changes in visual perception, such as increased attention to detail or visual hypersensitivity in ASD, are not due to impairments at early levels of retinal signal processing. En ligne : http://dx.doi.org/10.1002/aur.2823 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488
in Autism Research > 15-11 (November 2022) . - p.2026-2037[article] Electroretinography in adults with high-functioning autism spectrum disorder [Texte imprimé et/ou numérique] / Evelyn B. N. FRIEDEL, Auteur ; Mirjam SCHAFER, Auteur ; Dominique ENDRES, Auteur ; Simon MAIER, Auteur ; Kimon RUNGE, Auteur ; Michael BACH, Auteur ; Sven P. HEINRICH, Auteur ; Dieter EBERT, Auteur ; Katharina DOMSCHKE, Auteur ; Ludger TEBARTZ VAN ELST, Auteur ; Kathrin NICKEL, Auteur . - p.2026-2037.
Langues : Anglais (eng)
in Autism Research > 15-11 (November 2022) . - p.2026-2037
Mots-clés : Adult Humans Electroretinography/methods Retinal Ganglion Cells/physiology Autism Spectrum Disorder Photic Stimulation Retina/physiology Asd Erg PhNR a-wave autism spectrum disorder b-wave electroretinogram photopic negative response Index. décimale : PER Périodiques Résumé : The electroretinogram (ERG) allows the investigation of retinal signaling pathways and has increasingly been applied in individuals with mental disorders in search for potential biomarkers of neurodevelopmental disorders. Preceding ERG examinations in individuals with autism spectrum disorders (ASD) showed inconsistent results, which might be due to the small number of participants, heterogeneity of the ASD population, differences in age ranges, and stimulation methods. The aim of this study was to investigate functional retinal responses in adults with ASD by means of the light-adapted (photopic) ERG. Light-adapted ERG measurements were obtained with the RETeval® system applying three different stimulation protocols. In the final analysis, the ERG parameters a-wave, b-wave, the photopic negative response (PhNR), the photopic hill parameters as well as additional amplitude ratios were compared between 32 adults with high-functioning ASD and 31 non-autistic controls. Both groups were matched with regard to sex and age. No significant functional retinal differences in amplitude or peak time of the a- or b-wave, PhNR, the photopic hill parameters or the ERG-amplitude ratios could be detected in individuals with ASD compared to non-autistic participants. The absence of electrophysiological functional retinal alterations in ASD, suggests that changes in visual perception, such as increased attention to detail or visual hypersensitivity in ASD, are not due to impairments at early levels of retinal signal processing. En ligne : http://dx.doi.org/10.1002/aur.2823 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=488 Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model / H. DAI in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)
[article]
Titre : Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model Type de document : Texte imprimé et/ou numérique Auteurs : H. DAI, Auteur ; Carrie R. JACKSON, Auteur ; G. L. DAVIS, Auteur ; R. D. BLAKELY, Auteur ; D. G. MCMAHON, Auteur Article en page(s) : p.38 Langues : Anglais (eng) Mots-clés : Ala559Val coding substitution Anomalous dopamine efflux Attention-deficit/hyperactivity disorder Biomarker Dopamine transporter Electroretinogram Index. décimale : PER Périodiques Résumé : BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed. METHODS: Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice. RESULTS: Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D1 and D4 DA receptor agonists and suppressed in HOM mice by introducing D4 antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates. CONCLUSIONS: These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling. En ligne : http://dx.doi.org/10.1186/s11689-017-9215-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350
in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.38[article] Is dopamine transporter-mediated dopaminergic signaling in the retina a noninvasive biomarker for attention-deficit/ hyperactivity disorder? A study in a novel dopamine transporter variant Val559 transgenic mouse model [Texte imprimé et/ou numérique] / H. DAI, Auteur ; Carrie R. JACKSON, Auteur ; G. L. DAVIS, Auteur ; R. D. BLAKELY, Auteur ; D. G. MCMAHON, Auteur . - p.38.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.38
Mots-clés : Ala559Val coding substitution Anomalous dopamine efflux Attention-deficit/hyperactivity disorder Biomarker Dopamine transporter Electroretinogram Index. décimale : PER Périodiques Résumé : BACKGROUND: Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed. METHODS: Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice. RESULTS: Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D1 and D4 DA receptor agonists and suppressed in HOM mice by introducing D4 antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates. CONCLUSIONS: These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling. En ligne : http://dx.doi.org/10.1186/s11689-017-9215-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350