Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

Summary

Participation Requirements

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 AS...

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, DTI 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 five study visits. Primary Objective: The overall goal of the current study is to 1) Characterize the relationship between an individual's baseline local cortical GABA concentration, DTI 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: MEG: Evoked fields and Spectral Power MRS: GABA+/Cr concentrations in the left pSTC DTI: Diffusion tensor derived parameters in the auditory radiations and arcuate fasciculus. fcMRI: BOLD correlations across pre-defined ROIs. Secondary Endpoints: MEG: Inter-trial gamma-band coherence (ITC) and resting state alpha to gamma phase-amplitude coupling. SRS-2, CELF-5, EVT, PPVT, ADOS-2, ADI-R, VABS-III, WASI- II. Study Population: In the pilot phase of the study, we aim to enroll up to 20 healthy control adult participants. These healthy control young adult participants (age 18-25) will undergo imaging scans, cTBS, and MEG. They will additionally receive a medical history, brief neurological and physical exam; and complete an IQ assessment and the SRS-2 self-report. As the aim of the healthy control young adult portion of the study involves piloting procedures and tasks and confirming target engagement of active stimulation, the healthy control young adults participation will involve only 3 visits: An enrollment/screening/baseline visit and two cTBS visits (one with MRS/fMRI immediately before and after and one with MEG immediately before and after).As with the main phase of the study, 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. In the main phase of the study, we aim to collect a sample of 55 adolescents age 14-17 with ASD with complete data. In order to account for screen failures and participant attrition, we will recruit a total of 86 individuals (56% above the goal enrollment). Phase: N/A Description of Sites/Facilities Enrolling Participants: All visits will be outpatient and take place in the Clinical Center (Building 10) on NIH campus. Description of Study Intervention: Continuous theta burst stimulation (cTBS) will be applied using a MagPro X100 (MagVenture, Inc. Alpharetta, GA). The cTBS protocol consists of bursts of three pulses of 50 Hz stimulation repeated at 200 ms intervals (5 times per second) for 40 seconds (for a total of 600 pulses). Stimulation will be applied at an intensity of 80% of active motor threshold (AMT). Brainsight (Rogue Research) frameless neuronavigation system will be used to target the specific structural MRI-defined region of stimulation. Study Duration: 36 months Participant Duration: 2 months

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