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

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.

Study Overview

• Status: Recruiting
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Other: Speech discrimination

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elizabeth Smith, PhD; Phone Number: 5135171383; Email: elizabeth.smith3@cchmc.org
• Study Contact Backup: Name: Craig Erickson, MD; Phone Number: 5136366553; Email: craig.erickson@cchmc.org

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital
      • Contact: Elizabeth Smith, PhD; Phone Number: 5135171383; Email: elizabeth.smith3@cchmc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Speech Sounds; Participants listen to speech sounds while the investigators measure electrical and hemodynamic changes in the brain.	Other: Speech discrimination; Two different speech sounds are played at the same sound intensity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mullen Scales of Early Learning	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.	at 12 month, 18 month, and 24 month visits
Changes in oxygenated and deoxygenated hemoglobin concentration in response to sounds in language regions of the brain	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.	at 12 month, 18 month, and 24 month visits
Changes in amplitude of mismatch negativity response during sound discrimination	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.	at 12 month, 18 month, and 24 month visits
Changes in hearing thresholds	Hearing thresholds in dB as assessed using Conditioned Play Audiometry (CPA) or Visual Reinforced Audiometry (VRA) dependent on child age and developmental ability.	at 12 month, 18 month, and 24 month visits
Otoacoustic Emissions (OAEs)	Signals produced by excitation of hair cells in cochlea are measured for a range of frequencies.	at 12 month, 18 month, and 24 month visits
Changes in tympanometric pressure profile in the inner ear	Wide Band Tympanometry is completed to measure variability in tympanometric pressure for left and right ears that may affect hearing profile.	at 12 month, 18 month, and 24 month visits
Changes in LENA vocalizations and conversational turns	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'.	at 12 month, 18 month, and 24 month visits

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensory profile 2 Auditory Processing subtest	parent-report measure of child's behavioral responses to sounds in their environment	at 6 month, 12 month, 18 month, and 24 month visits
Sensory Profile 2 Attentional subtest	parent-report measure of child's awareness of and responses to sensory cues in their environment.	at 6 month, 12 month, 18 month, and 24 month visits

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: August 15, 2024
• First Submitted That Met QC Criteria: August 15, 2024
• First Posted (Actual): August 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, Inborn; Neurobehavioral Manifestations; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Intellectual Disability; Genetic Diseases, X-Linked; Sex Chromosome Disorders; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; X-Linked Intellectual Disability; Fragile X Syndrome; Physiological Phenomena; Vestibulocochlear Physiological Phenomena; Auditory Perception; Speech Perception
• Other Study ID Numbers: K23HD109375 Aim2; K23HD109375 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified information will be shared as required for NIH grant supported studies.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No