Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome
Abstract Background Autism spectrum disorders (ASD) encompass a wide array of debilitating symptoms, including sensory dysfunction and delayed language development. Auditory temporal processing is crucial for speech perception and language development. Abnormal development of temporal processing may...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Neurodevelopmental Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11689-023-09496-8 |
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| author | Katilynne Croom Jeffrey A. Rumschlag Michael A. Erickson Devin K. Binder Khaleel A. Razak |
| author_facet | Katilynne Croom Jeffrey A. Rumschlag Michael A. Erickson Devin K. Binder Khaleel A. Razak |
| author_sort | Katilynne Croom |
| collection | DOAJ |
| description | Abstract Background Autism spectrum disorders (ASD) encompass a wide array of debilitating symptoms, including sensory dysfunction and delayed language development. Auditory temporal processing is crucial for speech perception and language development. Abnormal development of temporal processing may account for the language impairments associated with ASD. Very little is known about the development of temporal processing in any animal model of ASD. Methods In the current study, we quantify auditory temporal processing throughout development in the Fmr1 knock-out (KO) mouse model of Fragile X Syndrome (FXS), a leading genetic cause of intellectual disability and ASD-associated behaviors. Using epidural electrodes in awake and freely moving wildtype (WT) and KO mice, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (gap-ASSR) paradigm. Mice were recorded at three different ages in a cross sectional design: postnatal (p)21, p30 and p60. Recordings were obtained from both auditory and frontal cortices. The gap-ASSR requires underlying neural generators to synchronize responses to gaps of different widths embedded in noise, providing an objective measure of temporal processing across genotypes and age groups. Results We present evidence that the frontal, but not auditory, cortex shows significant temporal processing deficits at p21 and p30, with poor ability to phase lock to rapid gaps in noise. Temporal processing was similar in both genotypes in adult mice. ERP amplitudes were larger in Fmr1 KO mice in both auditory and frontal cortex, consistent with ERP data in humans with FXS. Conclusions These data indicate cortical region-specific delays in temporal processing development in Fmr1 KO mice. Developmental delays in the ability of frontal cortex to follow rapid changes in sounds may shape language delays in FXS, and more broadly in ASD. |
| first_indexed | 2024-03-12T21:12:16Z |
| format | Article |
| id | doaj.art-bb240167ab984453b29c29cd6fb9a037 |
| institution | Directory Open Access Journal |
| issn | 1866-1955 |
| language | English |
| last_indexed | 2024-03-12T21:12:16Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj.art-bb240167ab984453b29c29cd6fb9a0372023-07-30T11:08:03ZengBMCJournal of Neurodevelopmental Disorders1866-19552023-07-0115111810.1186/s11689-023-09496-8Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndromeKatilynne Croom0Jeffrey A. Rumschlag1Michael A. Erickson2Devin K. Binder3Khaleel A. Razak4Graduate Neuroscience Program, University of CaliforniaDepartment of Otolaryngology-Head and Neck Surgery, Medical University of South CarolinaDepartment of Psychology, University of CaliforniaGraduate Neuroscience Program, University of CaliforniaGraduate Neuroscience Program, University of CaliforniaAbstract Background Autism spectrum disorders (ASD) encompass a wide array of debilitating symptoms, including sensory dysfunction and delayed language development. Auditory temporal processing is crucial for speech perception and language development. Abnormal development of temporal processing may account for the language impairments associated with ASD. Very little is known about the development of temporal processing in any animal model of ASD. Methods In the current study, we quantify auditory temporal processing throughout development in the Fmr1 knock-out (KO) mouse model of Fragile X Syndrome (FXS), a leading genetic cause of intellectual disability and ASD-associated behaviors. Using epidural electrodes in awake and freely moving wildtype (WT) and KO mice, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (gap-ASSR) paradigm. Mice were recorded at three different ages in a cross sectional design: postnatal (p)21, p30 and p60. Recordings were obtained from both auditory and frontal cortices. The gap-ASSR requires underlying neural generators to synchronize responses to gaps of different widths embedded in noise, providing an objective measure of temporal processing across genotypes and age groups. Results We present evidence that the frontal, but not auditory, cortex shows significant temporal processing deficits at p21 and p30, with poor ability to phase lock to rapid gaps in noise. Temporal processing was similar in both genotypes in adult mice. ERP amplitudes were larger in Fmr1 KO mice in both auditory and frontal cortex, consistent with ERP data in humans with FXS. Conclusions These data indicate cortical region-specific delays in temporal processing development in Fmr1 KO mice. Developmental delays in the ability of frontal cortex to follow rapid changes in sounds may shape language delays in FXS, and more broadly in ASD.https://doi.org/10.1186/s11689-023-09496-8Autism spectrum disordersFragile X syndromeSpeech processingTemporal processingSensory hypersensitivityLanguage |
| spellingShingle | Katilynne Croom Jeffrey A. Rumschlag Michael A. Erickson Devin K. Binder Khaleel A. Razak Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome Journal of Neurodevelopmental Disorders Autism spectrum disorders Fragile X syndrome Speech processing Temporal processing Sensory hypersensitivity Language |
| title | Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome |
| title_full | Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome |
| title_fullStr | Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome |
| title_full_unstemmed | Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome |
| title_short | Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome |
| title_sort | developmental delays in cortical auditory temporal processing in a mouse model of fragile x syndrome |
| topic | Autism spectrum disorders Fragile X syndrome Speech processing Temporal processing Sensory hypersensitivity Language |
| url | https://doi.org/10.1186/s11689-023-09496-8 |
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