Role of GABAergic Transmission in Auditory Processing in Autism Spectrum Disorder

Inclusion criteria

• Pilot Phase Inclusion criteria
• Ability to provide informed consent
• Age: 18-25 years
• Must meet the definition of "Healthy Control" having completed the screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers" or under protocol 17-M-0181, "Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies". Main Study Phase Inclusion criteria
• Ability to provide informed assent and parent consent (Parents of children enrolling on the study do not need to be able to speak English. A consent form is available in English or Spanish for parents of children who enroll.)
• Age: 11-17 years
• Community Diagnosis of ASD based on DSM-IV or DSM-5 criteria (reviewed by a member of the Neurodevelopmental and Behavioral Phenotyping Service)
• Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II). WASI-II will be used as a measure of intellectual function. Children will be included when FSIQ \> 70.
• Right-handed: to reduce heterogeneity.
• Hearing: Normal hearing in order to complete the behavioural assessments.

Exclusion criteria

• Participants will be screened to exclude individuals with co-occurring neurological or medical conditions that might confound the results, as well as to exclude subjects in whom MRI or rTMS might result in increased risk of side effects or complications. This accounts for the majority of the exclusion criteria listed: Exclusion criteria Participants will be screened to exclude individuals with neurological, psychological/behavioral or medical conditions, as well as to exclude subjects in whom MRI or rTMS might result in increased risk of side effects or complications. This accounts for the majority of the exclusion criteria listed: Pilot Phase
• Non-English Speakers
• Known Neurological Disorder
• Known Psychiatric Disorder
• Known genetic disorder (e.g., NF1, tuberous sclerosis), acquired neurologic disease (e.g. stroke, tumour), cerebral palsy, intracranial pathology or significant dysmorphology;
• History of fainting spells of unknown or undetermined etiology that might constitute seizures;
• History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy;
• Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.);
• Past or Current History of Tinnitus
• Any implant, prosthesis or other permanent alteration of the body that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
• Signs of increased intracranial pressure;
• Intracranial lesion (including incidental finding on MRI) that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
• History of any head trauma within 6 months of screening, or beyond 6 months prior to screening, history of head trauma with evidence of traumatic abnormality appearing on a brain scan, or with loss of consciousness \>5 minutes, or with other sequelae, excluding headache, lasting \> 24 hours.
• Participants who have received rTMS less than 7 days prior to enrollment;
• Individuals currently taking GABAergic medications or any other medication that, in the opinion of the investigator, significantly lowers seizure threshold;
• Individuals for whom it is not safe or appropriate to remain on a stable pharmacotherapy (for nonexclusionary medications) for six weeks prior to and over the course of their participation in the study;
• A current NIMH employee or staff or their immediate family member. Main Study Phase
• Non-English Speakers
• Known genetic disorder that is either associated with the ASD diagnosis or that in the opinion of the investigator may increase the risk to the participant or compromise the integrity of the data;
• Acquired neurologic disease (e.g. stroke, tumour), cerebral palsy, intracranial pathology or significant dysmorphology;
• History of fainting spells of unknown or undetermined etiology that might constitute seizures;
• History of seizures, diagnosis of epilepsy, or immediate (1st degree relative) family history epilepsy;
• Any progressive (e.g., neurodegenerative) neurological disorder;
• Chronic (particularly) uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.);
• Past or Current history of clinically significant tinnitus as determined by an audiologist or other-licensed clinician.
• Any implant, prosthesis or other permanent alteration of the body that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
• Signs of increased intracranial pressure;
• Intracranial lesion (including incidental finding on MRI) that, in the opinion of the investigator, would be unsafe with MRI or TMS or that would produce an artifact that would compromise the integrity of data;
• History of any head trauma within 6 months of screening, or beyond 6 months prior to screening, history of head trauma with evidence of traumatic abnormality appearing on a brain scan, or with loss of consciousness \>5 minutes, or with other sequelae, excluding headache, lasting \> 24 hours.
• Participants who have received prior rTMS;
• Active or History of psychosis, bipolar disorder, active severe substance use disorders (within the last month), have active suicidal intent or plan as detected on screening instruments or in the investigator team's opinion is likely to attempt suicide within 6 months;
• Individuals currently taking GABAergic medications or any other medication or medication change that, in the opinion of the investigator, significantly lowers seizure threshold;
• Past or present medical or neurological condition, disease, disorder, genetic finding, or injury that, in the opinion of the Investigator, may significantly increase the potential risks of study participation, reduce or compromise a subject's ability to fully comply with all study requirements for the duration of the study or may compromise the integrity of the data.