Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome / Elizabeth BERRY-KRAVIS ; Mark D. HARNETT ; Scott A. REINES ; Melody A REESE ; Abigail H OUTTERSON ; Claire MICHALAK ; Jeremiah FURMAN ; Mark E. GURNEY ; Lauren E ETHRIDGE in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 47 Titre : Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome Type de document : texte imprimé Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; Mark D. HARNETT, Auteur ; Scott A. REINES, Auteur ; Melody A REESE, Auteur ; Abigail H OUTTERSON, Auteur ; Claire MICHALAK, Auteur ; Jeremiah FURMAN, Auteur ; Mark E. GURNEY, Auteur ; Lauren E ETHRIDGE, Auteur Article en page(s) : 47 Langues : Anglais (eng) Mots-clés : Adult  Humans  Male  Middle Aged  Young Adult  Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism  *Electroencephalography  Evoked Potentials  Evoked Potentials, Auditory/drug effects  *Fragile X Syndrome/blood/drug therapy/physiopathology  Biomarker  Eeg  Fragile X syndrome  Pharmacokinetics  Zatolmilast  interests. M.D.H.and S.D.R. are paid consultants to Tetra Therapeutics. M.E.G. is  an employee of TetraTherapeutics, which is a wholly owned subsidiary of Shionogi  & Co., Ltd that has a financial interest in BPN14770. Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ? 200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS. En ligne : https://dx.doi.org/10.1186/s13229-024-00626-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Auditory N1 event-related potential amplitude is predictive of serum concentration of BPN14770 in fragile X syndrome [texte imprimé] / Elizabeth BERRY-KRAVIS, Auteur ; Mark D. HARNETT, Auteur ; Scott A. REINES, Auteur ; Melody A REESE, Auteur ; Abigail H OUTTERSON, Auteur ; Claire MICHALAK, Auteur ; Jeremiah FURMAN, Auteur ; Mark E. GURNEY, Auteur ; Lauren E ETHRIDGE, Auteur . - 47. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 47 Mots-clés : Adult  Humans  Male  Middle Aged  Young Adult  Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism  *Electroencephalography  Evoked Potentials  Evoked Potentials, Auditory/drug effects  *Fragile X Syndrome/blood/drug therapy/physiopathology  Biomarker  Eeg  Fragile X syndrome  Pharmacokinetics  Zatolmilast  interests. M.D.H.and S.D.R. are paid consultants to Tetra Therapeutics. M.E.G. is  an employee of TetraTherapeutics, which is a wholly owned subsidiary of Shionogi  & Co., Ltd that has a financial interest in BPN14770. Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a rare neurodevelopmental disorder caused by a CGG repeat expansion ? 200 repeats in 5' untranslated region of the FMR1 gene, leading to intellectual disability and cognitive difficulties, including in the domain of communication. A recent phase 2a clinical trial testing BPN14770, a phosphodiesterase 4D inhibitor, showed improved cognition in 30 adult males with FXS on drug relative to placebo. The initial study found significant improvements in clinical measures assessing cognition, language, and daily functioning in addition to marginal improvements in electroencephalography (EEG) results for the amplitude of the N1 event-related potential (ERP) component. These EEG results suggest BPN14770 improved neural hyperexcitability in FXS. The current study investigated the relationship between BPN14770 pharmacokinetics and the amplitude of the N1 ERP component from the initial data. Consistent with the original group-level finding post-period 1 of the study, participants who received BPN14770 in period 1 showed a significant correlation between N1 amplitude and serum concentration of BPN14770 measured at the end of period 1. These findings strengthen the validity of the original result, indicating that BPN14770 improves cognitive performance by modulating neural hyperexcitability. This study represents the first report of a significant correlation between a reliably abnormal EEG marker and serum concentration of a novel pharmaceutical in FXS. En ligne : https://dx.doi.org/10.1186/s13229-024-00626-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Erratum to: Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome / Lauren E ETHRIDGE in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 38p. Titre : Erratum to: Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome Type de document : texte imprimé Auteurs : Lauren E ETHRIDGE, Auteur ; Stormi P. WHITE, Auteur ; Matthew W. MOSCONI, Auteur ; Jing WANG, Auteur ; Ernest V. PEDAPATI, Auteur ; Craig ERICKSON, Auteur ; Matthew J. BYERLY, Auteur ; John A. SWEENEY, Auteur Article en page(s) : 38p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-017-0140-1.]. En ligne : http://dx.doi.org/10.1186/s13229-017-0150-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Erratum to: Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome [texte imprimé] / Lauren E ETHRIDGE, Auteur ; Stormi P. WHITE, Auteur ; Matthew W. MOSCONI, Auteur ; Jing WANG, Auteur ; Ernest V. PEDAPATI, Auteur ; Craig ERICKSON, Auteur ; Matthew J. BYERLY, Auteur ; John A. SWEENEY, Auteur . - 38p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 38p. Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-017-0140-1.]. En ligne : http://dx.doi.org/10.1186/s13229-017-0150-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome / Lauren E ETHRIDGE in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 22p. Titre : Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome Type de document : texte imprimé Auteurs : Lauren E ETHRIDGE, Auteur ; Stormi P. WHITE, Auteur ; Matthew W. MOSCONI, Auteur ; Jing WANG, Auteur ; Ernest V. PEDAPATI, Auteur ; Craig ERICKSON, Auteur ; Matthew J. BYERLY, Auteur ; John A. SWEENEY, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Chirp  Eeg  Fragile X syndrome  Gamma  Sensory Index. décimale : PER Périodiques Résumé : BACKGROUND: Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. METHODS: EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0-100 Hz over 2 s. RESULTS: Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. CONCLUSIONS: This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics. En ligne : http://dx.doi.org/10.1186/s13229-017-0140-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome [texte imprimé] / Lauren E ETHRIDGE, Auteur ; Stormi P. WHITE, Auteur ; Matthew W. MOSCONI, Auteur ; Jing WANG, Auteur ; Ernest V. PEDAPATI, Auteur ; Craig ERICKSON, Auteur ; Matthew J. BYERLY, Auteur ; John A. SWEENEY, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 22p. Mots-clés : Chirp  Eeg  Fragile X syndrome  Gamma  Sensory Index. décimale : PER Périodiques Résumé : BACKGROUND: Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. METHODS: EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0-100 Hz over 2 s. RESULTS: Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. CONCLUSIONS: This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics. En ligne : http://dx.doi.org/10.1186/s13229-017-0140-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome / Jing WANG in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.11 Titre : A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome Type de document : texte imprimé Auteurs : Jing WANG, Auteur ; Lauren E ETHRIDGE, Auteur ; Matthew W. MOSCONI, Auteur ; Stormi P. WHITE, Auteur ; Devin K. BINDER, Auteur ; Ernest V. PEDAPATI, Auteur ; Craig ERICKSON, Auteur ; Matthew J. BYERLY, Auteur ; John A. SWEENEY, Auteur Article en page(s) : p.11 Langues : Anglais (eng) Mots-clés : Cross-frequency coupling  Eeg  Fragile X syndrome  Gamma  Hyperexcitability  Top-down modulation Index. décimale : PER Périodiques Résumé : BACKGROUND: Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability. METHODS: We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants. RESULTS: FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS. CONCLUSIONS: Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability. En ligne : http://dx.doi.org/10.1186/s11689-017-9191-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome [texte imprimé] / Jing WANG, Auteur ; Lauren E ETHRIDGE, Auteur ; Matthew W. MOSCONI, Auteur ; Stormi P. WHITE, Auteur ; Devin K. BINDER, Auteur ; Ernest V. PEDAPATI, Auteur ; Craig ERICKSON, Auteur ; Matthew J. BYERLY, Auteur ; John A. SWEENEY, Auteur . - p.11. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.11 Mots-clés : Cross-frequency coupling  Eeg  Fragile X syndrome  Gamma  Hyperexcitability  Top-down modulation Index. décimale : PER Périodiques Résumé : BACKGROUND: Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability. METHODS: We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants. RESULTS: FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS. CONCLUSIONS: Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability. En ligne : http://dx.doi.org/10.1186/s11689-017-9191-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

Resting state EEG abnormalities in autism spectrum disorders / Jing WANG in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.24 Titre : Resting state EEG abnormalities in autism spectrum disorders Type de document : texte imprimé Auteurs : Jing WANG, Auteur ; Jamie BARSTEIN, Auteur ; Lauren E ETHRIDGE, Auteur ; Matthew W. MOSCONI, Auteur ; Yukari TAKARAE, Auteur ; John A. SWEENEY, Auteur Article en page(s) : p.24 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Resting state EEG abnormalities in autism spectrum disorders [texte imprimé] / Jing WANG, Auteur ; Jamie BARSTEIN, Auteur ; Lauren E ETHRIDGE, Auteur ; Matthew W. MOSCONI, Auteur ; Yukari TAKARAE, Auteur ; John A. SWEENEY, Auteur . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.24 Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are a group of complex and heterogeneous developmental disorders involving multiple neural system dysfunctions. In an effort to understand neurophysiological substrates, identify etiopathophysiologically distinct subgroups of patients, and track outcomes of novel treatments with translational biomarkers, EEG (electroencephalography) studies offer a promising research strategy in ASD. Resting-state EEG studies of ASD suggest a U-shaped profile of electrophysiological power alterations, with excessive power in low-frequency and high-frequency bands, abnormal functional connectivity, and enhanced power in the left hemisphere of the brain. In this review, we provide a summary of recent findings, discuss limitations in available research that may contribute to inconsistencies in the literature, and offer suggestions for future research in this area for advancing the understanding of ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-24 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome / Michael G. MARISCAL in Molecular Autism, 12 (2021)  

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