Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

Autism Spectrum Disorder Clinical Trial

Official title: Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

Status Recruiting

Clinical Trial 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 14-17 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....

Clinical Trial 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 14-17) with ASD.

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:

1. MEG: Inter-trial gamma-band coherence (ITC) and resting state alpha to gamma phase-amplitude coupling.

2. SRS-2, CELF-5, EVT-3, PPVT-5, ADOS-2 (if available), ADI-R, VABS-III, WASI- II, CBCL. ;

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive

• NCT number: NCT04798274
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Lindsay M Oberman, Ph.D.
• Phone: (301) 435-7962
• Email: lindsay.oberman@nih.gov
• Status: Recruiting
• Phase: N/A
• Start date: June 15, 2021
• Completion date: June 30, 2027