TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders

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.

Inclusion criteria

at Boston Children's Hospital (children):

• For ASD group:

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

Inclusion criteria

at Beth Israel Deaconess Medical Center (adults):

• For ASD group:

• Clinical diagnosis of a disorder on the autism spectrum.
• Assessment using the Autism Diagnostic Observation Schedule.
• 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.