TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders

Investigations of Neuroplasticity Mechanisms in Autism Spectrum Disorders

The main purpose is to study brain plasticity (the changes that occur in the brain through experience) in individuals with autism spectrum disorder (ASD). Research suggests that during development, the brains of individuals with ASD may change in response to their experiences differently than the brains of typically developing individuals. Investigators want to understand why and how this difference may contribute to the symptoms of ASD.

Study Overview

• Status: Completed
• Conditions: Intellectual Disability; Autism Spectrum Disorder
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation

Detailed Description

Autism Spectrum Disorders (ASD) are diagnosed clinically, based on key symptoms. As ASD phenotypic variability is large, and symptoms can manifest at different ages and degrees, the clinical diagnosis is challenging. To date, there remains an unmet need for a valid and reliable endophenotype that would facilitate ASD diagnosis early in life, enable efficient study of ASD risk factors, and eventually serve as a useful biomarker to inform the development of effective therapies and assess treatment response in future clinical trials.

As compared with behavioral or neuroimaging methods, transcranial magnetic stimulation (TMS) offers the advantage of providing behaviorally independent results that are largely unaffected by attention or cognitive ability. Therefore, a TMS based endophenotype may be applicable to all individuals across the autism spectrum.

At Boston Children's Hospital, each subject's participation in the study will consist of four visits: two screening visits, and two TMS sessions. At Beth Israel Deaconess Medical Center, each subject's participation will consist of three visits: one screening visit, and two TMS sessions. Each screening visit is expected to last between 2-3 hours, during which participants will first provide informed consent. Participants will then receive a thorough medical examination by a neurologist, and a neuropsychological evaluation (including IQ measures and ASD specific evaluations). If eligible to continue, participants will then come back for two identical TMS visits, that are spaced 1-5 weeks apart. These visits are expected to last between 3-4 hours, and include the TMS measures of brain plasticity.

• Study Type: Observational
• Enrollment (Actual): 164

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children and adults diagnosed with an Autism Spectrum Disorder (ASD), as well as controls.

Description

Inclusion Criteria at Boston Children's Hospital (children):

• For ASD group:

  1. Clinical diagnosis of a disorder on the autism spectrum.
  2. Assessment using the Autism Diagnostic Observation Schedule.
  3. Assessment using the Autism Diagnostic Interview-Revised.
  4. Children ages 6-16.
  5. IQ>70.
  6. Verbal.

Inclusion Criteria at Beth Israel Deaconess Medical Center (adults):

• For ASD group:

  1. Clinical diagnosis of a disorder on the autism spectrum.
  2. Assessment using the Autism Diagnostic Observation Schedule.
  3. Adults ages 21-65.

Exclusion Criteria:

• Intracranial pathology, cerebral palsy, history of severe head injury, significant dysmorphology, or known intracranial lesion.
• History of fainting spells of unknown or undetermined etiology.
• History of head injury resulting in prolonged loss of consciousness.
• History of seizures, diagnosis of epilepsy, or immediate family history of epilepsy.
• Any progressive neurological disorder or signs of intracranial pressure.
• Chronic uncontrolled medical conditions that may cause a medical emergency in case of a provoked seizure.
• Metal implants or devices.
• Substance abuse or dependence within the past six months.
• Certain prescription medications that decrease cortical seizure threshold.
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Autism Spectrum Disorder (ASD); Individuals diagnosed with an Autism Spectrum Disorder (ASD) will receive transcranial magnetic stimulation (TMS) to measure brain plasticity.	Device: Transcranial Magnetic Stimulation; Single pulses of TMS as well as continuous theta burst stimulation (cTBS) will be applied to the motor cortex.
Healthy Control; Typically developing individuals without a history of autism will receive transcranial magnetic stimulation (TMS) to measure brain plasticity.	Device: Transcranial Magnetic Stimulation; Single pulses of TMS as well as continuous theta burst stimulation (cTBS) will be applied to the motor cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of baseline TMS-induced measures of human synaptic plasticity	Synaptic plasticity will be measured using the MEPs in response to cTBS. Baseline MEPs will be calculated before cTBS, and at different time points following cTBS up to 120 minutes. The investigators will compare post-cTBS MEPs to the baseline MEPs to calculate the percent change from baseline.	120 minutes after cTBS

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: National Institute of Mental Health (NIMH); Beth Israel Deaconess Medical Center
• Investigators: Principal Investigator: Alvaro Pascual-Leone, MD, PhD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): April 1, 2020
• Study Completion (Actual): July 1, 2020

Study Registration Dates

• First Submitted: May 13, 2016
• First Submitted That Met QC Criteria: July 18, 2016
• First Posted (Estimate): July 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 4, 2020
• Last Update Submitted That Met QC Criteria: December 3, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: ASD; Autism; Transcranial Magnetic Stimulation; Autism Spectrum Disorder; Autistic Disorder; TMS; Pervasive Development Disorders; Asperger's Syndrome; Pervasive Child Development Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Disease; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Intellectual Disability
• Other Study ID Numbers: 00014965; 1R01MH100186-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No