scholarly journals Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability

2021 ◽  
Author(s):  
Carol Wilkinson ◽  
Charles A Nelson
Keyword(s):  
Fragile X Syndrome ◽  
Mouse Models ◽  
Resting State ◽  
Fragile X ◽  
Pearson Correlation ◽  
Language Ability ◽  
Compensatory Mechanisms ◽  
Clinical Biomarkers ◽  
Gamma Power ◽  
Periodic Components

Abstract Background: The lack of robust and reliable clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit alterations in resting state and task-related activity. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated with core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. Methods: Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (2.5-7 years old, n=11) and compared with both age-matched (n=12) and cognitive-matched (n=12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30-50Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. Results: FXS participants showed increased power in the beta/gamma range (~25-50Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. Limitations: The study sample size was small, although comparable to other human studies in rare-genetic disorders. Findings are also limited to males in the age range studied. Conclusions: Resting-state EEG measures from this study in young boys with FXS identified similar increases in gamma power previously reported in adults and mouse models. The observed positive association between resting state aperiodic gamma power and language development supports hypotheses that alterations in some EEG measures may reflect ongoing compensatory mechanisms.

scholarly journals Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carol L. Wilkinson ◽  
Charles A. Nelson
Keyword(s):  
Fragile X Syndrome ◽  
Mouse Models ◽  
Resting State ◽  
Fragile X ◽  
Pearson Correlation ◽  
Language Ability ◽  
Compensatory Mechanisms ◽  
Clinical Biomarkers ◽  
Gamma Power ◽  
Periodic Components

Abstract Background The lack of robust and reliable clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit alterations in resting state and task-related activity. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated with core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. Methods Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (2.5–7 years old, n = 11) and compared with both age-matched (n = 12) and cognitive-matched (n = 12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30 and 50 Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. Results FXS participants showed increased power in the beta/gamma range (~ 25–50 Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. Limitations The study sample size was small, although comparable to other human studies in rare-genetic disorders. Findings are also limited to males in the age range studied. Conclusions Resting-state EEG measures from this study in young boys with FXS identified similar increases in gamma power previously reported in adults and mouse models. The observed positive association between resting state aperiodic gamma power and language development supports hypotheses that alterations in some EEG measures may reflect ongoing compensatory mechanisms.

scholarly journals Increased aperiodic gamma power in young boys with Fragile X Syndrome is associated with better language ability

2020 ◽  
Author(s):  
Carol Wilkinson ◽  
Charles A Nelson
Keyword(s):  
Fragile X Syndrome ◽  
Mouse Models ◽  
Resting State ◽  
Fragile X ◽  
Pearson Correlation ◽  
Language Ability ◽  
Permutation Testing ◽  
Clinical Biomarkers ◽  
Gamma Power ◽  
Periodic Components

Abstract Background: The lack of identified clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit increased resting-state gamma power. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated to core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. Methods: Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (32-84 months old, n=11) and compared with both age-matched (n=12) and cognitive-matched (n=12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30-50Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. Results: FXS participants showed increased power in the beta/gamma range (~25-50Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. Limitations: The study sample size was small, although comparable to other human studies in rare-genetic disorders. Findings are also limited to males in the age range studied. Conclusions: Resting-state EEG measures from this study in young boys with FXS identified similar increases in gamma power previously reported in adults and mouse models. The observed positive association between aperiodic gamma power and language supports hypotheses that alterations in some EEG measures may reflect ongoing compensation.

scholarly journals Increased aperiodic gamma power in young boys with Fragile X is associated with better language ability

2020 ◽  
Author(s):  
Carol L. Wilkinson ◽  
Charles A. Nelson
Keyword(s):  
Mouse Models ◽  
Resting State ◽  
Fragile X ◽  
Pearson Correlation ◽  
Parent Report ◽  
Language Ability ◽  
Permutation Testing ◽  
Clinical Biomarkers ◽  
Gamma Power ◽  
Periodic Components

ABSTRACTThe lack of identified clinical biomarkers in Fragile X Syndrome (FXS), the most common inherited form of intellectual disability, has limited the successful translation of bench-to-bedside therapeutics. While numerous drugs have shown promise in reversing synaptic and behavioral phenotypes in mouse models of FXS, none have demonstrated clinical efficacy in humans. Electroencephalographic (EEG) measures have been identified as candidate biomarkers as EEG recordings of both adults with FXS and mouse models of FXS consistently exhibit increased resting-state gamma power. However, the developmental timing of these EEG differences is not known as thus far EEG studies have not focused on young children with FXS. Further, understanding how EEG differences are associated to core symptoms of FXS is crucial to successful use of EEG as a biomarker, and may improve our understanding of the disorder. Resting-state EEG was collected from FXS boys with full mutation of Fmr1 (32-84 months old, n=11) and compared with both age-matched (n=12) and cognitive-matched (n=12) typically developing boys. Power spectra (including aperiodic and periodic components) were compared using non-parametric cluster-based permutation testing. Associations between 30-50Hz gamma power and cognitive, language, and behavioral measures were evaluated using Pearson correlation and linear regression with age as a covariate. FXS participants showed increased power in the beta/gamma range (∼25-50Hz) across multiple brain regions. Both a reduction in the aperiodic (1/f) slope and increase in beta/gamma periodic activity contributed to the significant increase in high-frequency power. Increased gamma power, driven by the aperiodic component, was associated with better language ability in the FXS group. No association was observed between gamma power and parent report measures of behavioral challenges, sensory hypersensitivities, or adaptive behaviors. The observed positive association between increased aperiodic gamma power and language supports hypotheses that increased E/I ratios observed in FXS mouse models may reflect beneficial compensation.

scholarly journals PDE-4 Inhibition Rescues Aberrant Synaptic Plasticity in Drosophila and Mouse Models of Fragile X Syndrome

2015 ◽  
Vol 35 (1) ◽  
pp. 396-408 ◽  
Author(s):  
C. H. Choi ◽  
B. P. Schoenfeld ◽  
E. D. Weisz ◽  
A. J. Bell ◽  
D. B. Chambers ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Fragile X Syndrome ◽  
Mouse Models ◽  
Fragile X

scholarly journals Deficient Sleep in Mouse Models of Fragile X Syndrome

2017 ◽  
Vol 10 ◽  
Author(s):  
R. Michelle Saré ◽  
Lee Harkless ◽  
Merlin Levine ◽  
Anita Torossian ◽  
Carrie A. Sheeler ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Mouse Models ◽  
Fragile X

scholarly journals Baclofen-Associated Neurophysiologic Target Engagement Across Species in Fragile X Syndrome

2021 ◽  
Author(s):  
Carrie R. Jonak ◽  
Ernest V. Pedapati ◽  
Lauren M. Schmitt ◽  
Samantha A. Assad ◽  
Manbir S. Sandhu ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Sensory Processing ◽  
Fragile X ◽  
Repetitive Behavior ◽  
Gamma Activity ◽  
Multielectrode Array ◽  
Target Engagement ◽  
Human Experiments ◽  
Gamma Power ◽  
Delayed Language Development

Abstract Background: Fragile X Syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. Methods: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABAB selective agonist racemic baclofen (RBAC). Results: In Fmr1 KO mice and in humans with FXS, baclofen use was synchronously associated with suppression of elevated gamma power and increase in theta power at rest. In the Frm1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. Conclusions: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. Trial Registration: The human experiments are registered under NCT02998151.

Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome

2002 ◽  
Vol 927 (1) ◽  
pp. 8-17 ◽  
Author(s):  
Darci M. Nielsen ◽  
William J. Derber ◽  
Danielle A. McClellan ◽  
Linda S. Crnic
Keyword(s):  
Fragile X Syndrome ◽  
Mouse Models ◽  
Startle Response ◽  
Mutant Mouse ◽  
Fragile X ◽  
Auditory Startle Response

scholarly journals Resting-state fMRI study of patients with fragile X syndrome

2017 ◽  
Vol 886 ◽  
pp. 012007 ◽  
Author(s):  
E Isanova ◽  
E Petrovskiy ◽  
A Savelov ◽  
D Yudkin ◽  
A Tulupov
Keyword(s):  
Fragile X Syndrome ◽  
Resting State ◽  
Fragile X ◽  
Resting State Fmri ◽  
Fmri Study

scholarly journals Influences on Maternal Responsivity in Mothers of Children With Fragile X Syndrome

2013 ◽  
Vol 118 (4) ◽  
pp. 310-326 ◽  
Author(s):  
Audra M. Sterling ◽  
Steven F. Warren ◽  
Nancy Brady ◽  
Kandace Fleming
Keyword(s):  
Young Children ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Language Ability ◽  
Standardized Assessments ◽  
Developmental Level ◽  
General Measure ◽  
Maternal Responsivity ◽  
Video Observations ◽  
And Behavior

Abstract This study investigated the influence of maternal and child variables on the maternal responsivity of 55 mothers with young children with fragile X syndrome. Data included video observations of mother-child interactions in four different contexts, standardized assessments with the children, and standardized questionnaires for the mothers. The video observations were coded for child communication acts; maternal responsivity was coded at two levels: a more general measure and a behavior-by-behavior measure. Results indicated that child developmental level and language ability strongly influenced behavior-by-behavior responsivity, while maternal IQ was the strongest predictor of both general and behavior-by-behavior responsivity, after controlling for child developmental level.

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