Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder
- Conditions
- Autism Spectrum Disorder
- Interventions
- Device: Continuous Theta Burst Stimulation
- Registration Number
- NCT04798274
- Lead Sponsor
- National Institute of Mental Health (NIMH)
- Brief Summary
Background:
Autism spectrum disorder (ASD) is a complex neurodevelopmental syndrome. Researchers think brain development may be controlled by gamma-aminobutyric acid (GABA). They want to learn how abnormalities in the GABA system may contribute to ASD.
Objective:
To see if repetitive transcranial magnetic stimulation (rTMS) creates short-term changes in how different parts of the brain communicate.
Eligibility:
Right-handed people ages 11-17 with ASD, and healthy volunteers ages 18-25.
Design:
Participants will be screened with:
Medical history
Physical exam
Medicine review
Neurological exam
Psychological tests and rating scales
Forms and surveys.
Participants will have a hearing test and ear exam.
Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that moves in and out of the MRI scanner. They may look at a screen while in the scanner. A coil will be placed over their head.
Participants will have magnetic resonance spectroscopy. It takes pictures of chemicals in the brain using the MRI scanner.
Participants will have magnetoencephalography. They will sit in a chair. A helmet with magnetic field sensors will be placed on their head.
Participants will have TMS. A wire coil will be held on their scalp. A brief electrical current will pass through the coil.
Participants will have electromyography. Sticky pad electrodes will be placed on the skin during TMS. The electrical activity of their muscles will be measured.
Participants will have rTMS. It uses short bursts of magnetic pulses to affect brain activity.
ASD participants will have 7 visits over 2-3 months. Healthy volunteers will have 3 visits over 3-4 weeks....
- Detailed Description
Study Description:
This will be a within-subject, controlled, proof-of-mechanism study.
Objectives:
The study aims to evaluate the relationship between local GABA concentration, structural and functional network connectivity and MEG measures of auditory and language processing in adolescents with ASD and the acute impact of a single session of continuous theta burst stimulation over left posterior superior temporal cortex (pSTC) on these measures. We hypothesize that GABA concentrations, DWI measures of tissue microstructure and fcMRI obtained BOLD correlations within the language network will significantly contribute to the prediction model for MEG indices of auditory and language processing. Participation in the study involves about seven study visits. Some of the visits may be split up to shorten the length of session and limit fatigue. Visits will be scheduled about once a week. All visits must be completed within six months of the date of enrollment.
Primary Objective: The overall goal of the current study is to 1) Characterize the relationship between an individual's baseline local cortical GABA concentration, DWI measures of auditory and language network tissue microstructure, and fcMRI indices of local and long-range network functional connectivity (predictor variables) and MEG indices of auditory and language processing (dependent variables).
Secondary Objectives: 2) Evaluate the impact of a single session of cTBS over the left pSTC on these MRS and MEG indices in adolescents (age 11-17) with ASD.
Exploratory Objective: 3) Characterize the relationship between the neuroimaging and electrophysiological indices obtained in this study and baseline behavioral symptom presentation.
Endpoints:
Primary Endpoints:
1. MEG: Evoked fields and Spectral Power
2. MRS: GABA+/Cr concentrations in the left pSTC
3. DWI: Diffusion derived parameters in the auditory radiations and arcuate fasciculus.
4. fcMRI: BOLD correlations across pre-defined ROIs.
Secondary Endpoints:
a. MEG: Inter-trial gamma-band coherence (ITC) and resting state alpha to gamma phase-amplitude coupling.
Exploratory Endpoints:
a. SRS-2, CELF-5, EVT-3, PPVT-5, ADOS-2 (if available), ADI-R, VABS-III, WASI-II, CBCL, EDI.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 106
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sham cTBS Continuous Theta Burst Stimulation This intervention involves sham (placebo) repetitive transcranial magnetic stimulation. The coil is blinded, but does not emit any magnetic field Active cTBS Continuous Theta Burst Stimulation This intervention involves active repetitive magnetic stimulation. The coil emits a magnetic field
- Primary Outcome Measures
Name Time Method MRS immediately pre and post rTMS GABA+/Cr concentrations in the left pSTC
MEG immediately pre and post rTMS Evoked fields and Spectral Power
fcMRI immediately pre and post rTMS BOLD correlations across pre-defined ROIs.
DTI immediately pre and post rTMS Diffusion tensor derived parameters in the auditory radiations and arcuate fasciculus.
- Secondary Outcome Measures
Name Time Method Neuropsychological Assessments Baseline SRS-2, CELF-5, EVT, PPVT, ADOS-2, ADI-R, VABS-III, WASI-II.
MEG immediately pre and post rTMS Inter-trial gamma-band coherence (ITC) and resting state alpha to gamma phase-amplitude coupling.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States