Fragile X Syndrome (FXS) is a complex neurodevelopmental disorder caused by a mutation on the X chromosome. Scientists have investigated FXS extensively in both humans and animals. Thus far, phenotypic rescue in animal models has not resulted in treatment breakthroughs in humans, though some important discoveries have been made. Research has shown that individuals with FXS process sounds differently than those in the typical population, and they also show baseline differences in brain activity, including high gamma activity, increased theta activity, and decreased alpha activity. The investigators' central hypothesis is that these alterations in brain activity (specifically alpha and gamma activity) impair the brain's ability to process new information, thereby impeding cognitive functioning and increasing sensory sensitivity. The investigators propose that auditory entrainment, a technique that involves playing special sounds through headphones, will normalize brain activity in individuals with FXS and lead to increased cognitive function and decreased sensory hypersensitivity.
FXS Cohort: 1) Aged 5-10 years, inclusive; 2) Patient has full FMR1 mutation confirmed by genetic testing.
ASD Cohort: 1) Aged 5-10 years, inclusive; 2) Have no known genetic mutation; 3) Have documentation of ASD diagnosis; 4) Score ≤ 15 on SCQ screen; 5) Be in good health per investigator.
TDC Cohort: 1) Aged 5-10 years, inclusive; 2) Have no known genetic mutation; 3) Have documentation of ASD diagnosis; 4) Score ≤ 15 on SCQ screen; 5) Be in good health per investigator; 6) Patient has met normal developmental milestones; Patient has no family history of heritable neuropsychiatric disorders; 7) Patient has an IQ greater than 85 on the Stanford-Binet; 8) Score ≤8 on an SCQ screen.
All subjects: 1) Patient has auditory or visual impairments that cannot be corrected; 2) History of substance abuse or dependence within the past 6 months
Crossover
Alpha Auditory Entrainment
Other interventionAlpha Brainwave Entrainment (AAE) stimulus: starts at high theta range (7-Hz) through high alpha (13-Hz) in 2 Hz steps on a 500 Hz sine carrier tone Target frequency: 10 Hz Delivery: headphones/speakers
Sham
Other interventionSham stimulus: carrier tone alone Target frequency: N/A Delivery: headphones/speakers
Alpha auditory entrainment versus sham effect on Word Learning Index during the Statistical Learning Passive Task.
The Statistical Learning Passive Task uses an EEG-based measure of neural entrainment that uses inter-trial coherence (ITC) to calculate Word Learning Index (WLI). Patterns of EEG phase-locking, corresponding to a shift in processing from raw syllable units to cohesive words, reflect gradual statistical learning in the brain. The WLI effect can be quantified by creating a ratio of the inter-trail coherence for words versus syllables, as follows: WLI = Inter-trial Coherence word rate / Inter-trial Coherence syllable rate A higher WLI indicates a relatively stronger response to tri-syllabic nonwords compared to raw syllables, reflecting stronger word segmentation due to statistical learning.
Alpha auditory entrainment versus sham effect on the Behavior Learning Effect during the Statistical Learning Active Task.
The Active SL Task based measure uses reaction time to estimate a behavioral measure of SL, the Behavioral Learning Effect BLE. BLE values indicate greater proportional facilitation to predictable words in the stream, indicative of stronger SL at the individual level. The Behavioral Learning effect is quantified as follows: BLE (in ms) = (Reaction time target syllable position 1)-(Reaction time target syllable position 3) Larger BLE values indicate greater proportional facilitation to predictable words in the stream, indicative of stronger SL at the individual level.
Click on the lead sponsor to view all of their trials.
Children's Hospital Medical Center, Cincinnati
Lead sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborator
