Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
Condition: Autism Spectrum Disorder; Intellectual Disability
MeSH terms: Intellectual Disability; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      Autism Spectrum Disorder (ASD) is the most prevalent of the developmental disorders and their
      incidence is rising. However, the variability in the behavioral symptoms is large. In part
      for these reasons, the ASD clinical diagnosis is challenging and often is not made until 3-5
      years of age. Thus, there remains an unmet need for a valid and reliable marker which would
      facilitate ASD diagnosis early in life, enable efficient study of ASD risk factors, and
      eventually serve as a useful marker to inform the development of effective therapies and
      assess treatment response in future clinical trials. The specific brain based marker that
      investigators are currently evaluating is brain plasticity (the changes that occur in your
      brain through experience). Investigators measure brain plasticity using noninvasive brain
      stimulation including transcranial magnetic stimulation (TMS) combined with brain imaging,
      EEG, and behavioral outcome measures. Their work to date demonstrates the potential utility
      of these techniques in higher-functioning adolescents and adults with ASD, and pilot data
      support the feasibility and safety of applying the same measures to children and lower
      functioning individuals.

      In this study, investigators will evaluate the validity of this marker in low- and
      high-functioning adults with ASD, in low- and high-functioning children with ASD, and assess
      the reliability of this marker.
    

Detailed description: 
      The clinical, social and financial burden of Autism Spectrum Disorder (ASD) is staggering.
      They are the most prevalent of the developmental disorders and their incidence is rising.
      However, the ASD phenotype variability is large, and ASD symptoms can manifest over a range
      of ages and to different degrees. In part for these reasons, the ASD clinical diagnosis is
      challenging and often is not made until 3-5 years of age. Thus, there remains an unmet need
      for a valid and reliable endophenotype which 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. The overarching goal of this proposal is to explore the utility of
      transcranial magnetic stimulation (TMS) measures of brain plasticity as a novel
      neurophysiologic endophenotype in high- and low-functioning adults and children with ASD.

      Investigators' work to date demonstrates the potential utility of these measures in
      higher-functioning adults with ASD, and pilot data support the feasibility and safety of
      applying the same measures to children and lower functioning individuals in whom the value of
      such an endophenotype would be particularly high. Investigators thus propose to apply
      single-pulse TMS to evaluate the modulation in corticospinal reactivity induced by a specific
      repetitive TMS protocol known as theta burst stimulation (TBS). The comparison of the motor
      responses induced by single-pulse TMS before and following TBS is a unique noninvasive
      measure of brain plasticity in humans, and investigators have found that it shows a reliable
      abnormality in high-functioning adult individuals with ASD.

      Each subject's participation in the study will consist of three visits: a screening visit and
      two identical study visits 1-3 weeks apart. Each visit will last for approximately 2 hours.
      During the first study visit the participants will provide informed consent. patients will
      then receive a thorough medical history and neurological and physical exam by a licensed
      physician with training in pediatric medicine. This will evaluate for underlying neurological
      disorders that would be exclusionary (e.g. motor impairments, epilepsy, medication
      contraindications etc.) All subjects will also complete a neuropsychological evaluation
      including IQ and ASD specific evaluations. If eligible to continue, the participant will then
      return within two weeks to undergo the first TMS evaluation. The TMS procedure will then be
      repeated 1-3 weeks later. The two identical TMS study visits aim to address reliability of
      the TMS-based measures: Investigators hypothesize that the TMS measures will be consistent
      across sessions within all study groups (ASD and controls, adults and children, low- and
      high-functioning individuals). Such test-retest reliability data are critical to explore the
      utility of the TMS measures as a potential marker for diagnosis and therapeutic efficacy of
      an intervention. Investigators thus anticipate that data from the proposed studies will
      address an important need for a rapid, noninvasive, reliable and safe endophenotype available
      to patients with ASD across ages and level of function.
    

Observational model: Other
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        We will study a total of 120 individuals with ASD. We will also evaluate a total of 120
        controls. Ages 6 - 45
      
Keywords: TMS; Autism Spectrum Disorders; Plasticity