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Tracking Early Emergence of Sound Perception Impairments in FXS With Multimodal fNIRS/EEG-Preschool Age

Not Applicable
Recruiting
Conditions
Fragile X Syndrome
Interventions
Other: Speech discrimination
Registration Number
NCT05957549
Lead Sponsor
Children's Hospital Medical Center, Cincinnati
Brief Summary

Individuals with Fragile X Syndrome show differences in how they understand and learn language from infancy. They frequently have lifelong delays in speech and language as well. In addition, they experience other auditory symptoms, including being very sensitive to certain sounds as well as being more sensitive than others to loud sounds. The underlying brain activity for sound perception and speech learning in Fragile X is not well understood, especially in the infant, toddler, and preschool years. This study uses behavioral assessment of speech and language abilities, neuroimaging, and hearing tests to understand how speech and hearing are different in children with Fragile X Syndrome.

Detailed Description

Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism and is associated with extremely high risk for early delays in speech and language. While early childhood is essential for speech and language development, neural mechanisms for language impairments have been studied entirely in older children and adults with FXS. Therefore, markers for speech and language impairments are unavailable in young children with FXS to predict severity, test potential mechanisms, and track response to intervention. The investigators have identified a hallmark brain-based phenotype of hyperresponsiveness to sounds in adolescents and adults with FXS. This fundamental alteration in cortical responses to sound could influence early language delays, but this phenotype has not been explored in infants or toddlers with FXS.

Specifically, in this study the investigators will use simultaneous EEG/fNIRS during presentation of simple speech, stories, and nonspeech sounds to quantify and localize auditory hypersensitivity and neural differentiation in 30 preschoolers with FXS. The investigators will assess specificity through comparison with 30 typically developing controls and 30 mental-age matched children with a history of premature birth and language delays.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria
  • Diagnoses of Fragile X Syndrome, Typical Development, or History of Premature Birth
  • able to sit independently
  • English is spoken at home
Exclusion Criteria
  • For all participants: no seizures in the past 6 months
  • For typical development group and Fragile X group: not born prior to 32 weeks gestation

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Speech SoundsSpeech discriminationParticipants listen to speech sounds while the investigators measure electrical and hemodynamic changes in the brain.
Primary Outcome Measures
NameTimeMethod
Change in Mullen Scales of Early Learningat single study visit between ages of 2-4 years inclusive

change in Mullen Scales scores (age-corrected) from baseline on all subscales, including Expressive Language, Receptive Language, FIne Motor, Gross Motor, and Visual Reception. T-Scores from the Mullen Scales of Early Learning (MSEL) have a mean of 50 and a standard deviation of 10. Range=20-80. Higher scores indicate more advanced developmental skills.

Changes in oxygenated and deoxygenated hemoglobin concentration in response to sounds in language regions of the brainat single study visit between ages of 2-4 years inclusive

Relative increase in oxygenated versus deoxygenated hemoglobin for no sounds, low intensity sounds, and medium intensity sounds. Measured via functional Near Infrared Spectroscopy with optodes placed over frontal, temporal, and parietal language regions.

Changes in amplitude of mismatch negativity response during sound discriminationat single study visit between ages of 2-4 years inclusive

Electroencephalography is measured over the scalp while participant listens to speech sounds with infrequent "oddball" stimuli. Amplitude of the P100 for all stimuli as well as amplitude of the mismatch negativity response (frequent minus infrequent response) as well as change in these metrics over development are tracked in all groups.

Changes in hearing thresholdsat single study visit between ages of 2-4 years inclusive

Hearing thresholds in dB as assessed using Conditioned Play Audiometry (CPA) or Visual Reinforced Audiometry (VRA) dependent on child age and developmental ability.

Otoacoustic Emissions (OAEs)at single study visit between ages of 2-4 years inclusive

Signals produced by excitation of hair cells in cochlea are measured for a range of frequencies.

Changes in tympanometric pressure profile in the inner earat single study visit between ages of 2-4 years inclusive

Wide Band Tympanometry is completed to measure variability in tympanometric pressure for left and right ears that may affect hearing profile.

Secondary Outcome Measures
NameTimeMethod
Sensory profile 2 Auditory Processing subtestat single study visit between ages of 2-4 years inclusive

parent-report measure of child's behavioral responses to sounds in their environment

Sensory Profile 2 Attentional subtestat single study visit between ages of 2-4 years inclusive

parent-report measure of child's awareness of and responses to sensory cues in their environment.

Trial Locations

Locations (1)

Cincinnati Children'S Hospital

🇺🇸

Cincinnati, Ohio, United States

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