Fragile X Syndrome
Conditions
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 and toddler 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 infancy 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 infants and toddlers 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 infants and toddlers, including 15 with FXS and 15 controls. Infants will complete visits at different ages, with possible visits at 6 months, 12 months, 18 months, and 24 months, so that changes with development can be tracked over time.
Interventions
Two different speech sounds are played at the same sound intensity.
Sponsors
Children's Hospital Medical Center, Cincinnati
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 26 Months
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mullen Scales of Early Learning | at 12 month, 18 month, and 24 month visits | 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 brain | at 12 month, 18 month, and 24 month visits | 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 discrimination | at 12 month, 18 month, and 24 month visits | 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 thresholds | at 12 month, 18 month, and 24 month visits | 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 12 month, 18 month, and 24 month visits | Signals produced by excitation of hair cells in cochlea are measured for a range of frequencies. |
| Changes in tympanometric pressure profile in the inner ear | at 12 month, 18 month, and 24 month visits | Wide Band Tympanometry is completed to measure variability in tympanometric pressure for left and right ears that may affect hearing profile. |
| Changes in LENA vocalizations and conversational turns | at 12 month, 18 month, and 24 month visits | LENA is a voice recording system and proprietary program that records a child's home language environment. This recording is then digitally processed to model aspects of the child's own vocalizations and those of others'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensory profile 2 Auditory Processing subtest | at 6 month, 12 month, 18 month, and 24 month visits | parent-report measure of child's behavioral responses to sounds in their environment |
| Sensory Profile 2 Attentional subtest | at 6 month, 12 month, 18 month, and 24 month visits | parent-report measure of child's awareness of and responses to sensory cues in their environment. |
Countries
United States
Contacts
CONTACTElizabeth Smith, PhD
CONTACTCraig Erickson, MD
Outcome results
None listed