Transcranial Magnetic Stimulation for Autism Spectrum Disorder

Overseen By Vaughn R Steele, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Psychotropics, Anticonvulsants

Disqualifiers: Neurological disorder, Major medical condition, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 3 weeks

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this observational study is to test the modulation effect of different transcranial magnetic stimulation (TMS) on the neural network supporting our ability to create mental representations of others (also known as mentalizing) in young adults with autism. The main question it aims to answers is can stimulation of the right temporoparietal junction can change brain activity related to mentalizing during social interaction in the stimulation area and other brain areas connected to it. Researchers will compare results to a group of individuals without autism to see if the patterns of neural activity change are similar between the groups. Participants will undergo assessment of their clinical traits and social skills and baseline MRI scan. They will attend three additional visits that include TMS session and functional MRI scans before and right after TMS.

Will I have to stop taking my current medications?

The trial requires that participants with autism have a stable medication treatment for at least 4 weeks before joining the study. If you are on medications, you should not change them during this period before the trial.

What data supports the effectiveness of the treatment rTMS for autism spectrum disorder?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve attention, reduce repetitive behavior, and decrease irritability in individuals with autism. It has also been found to improve depressive symptoms in those with both autism and depression, suggesting potential benefits for core autism symptoms. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including its repetitive form (rTMS), is generally considered safe for humans, with guidelines established to minimize risks. While it has been associated with mild side effects, such as headaches or discomfort, and rare cases of seizures, it is well tolerated in both healthy individuals and those with conditions like depression and autism spectrum disorder. ^{1 6 7 8 9}

How does transcranial magnetic stimulation differ from other treatments for autism spectrum disorder?

Transcranial magnetic stimulation (TMS) is unique because it is a noninvasive brain stimulation technique that uses magnetic fields to stimulate nerve cells in the brain, which is different from traditional drug therapies. It has shown potential in improving symptoms of autism spectrum disorder (ASD) by enhancing cognitive abilities, emotional recognition, and reducing repetitive behaviors, which are not typically targeted by standard treatments. ^{1 2 3 6 10}

Research Team

Vaughn Steele, MD

Principal Investigator

Yale University

Michal Assaf, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for young adults with Autism Spectrum Disorder (ASD) who can undergo MRI scans and TMS sessions. It's not suitable for individuals without ASD or those who cannot safely have these procedures due to other medical conditions.

Inclusion Criteria

I don't have psychiatric disorders, except maybe simple phobia, and no family history of ASD.

None of my close relatives have had hereditary neurological disorders.

I have never had a serious head injury.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo assessment of clinical traits, social skills, and a baseline MRI scan

1 week

1 visit (in-person)

Treatment

Participants receive three rTMS sessions (excitatory, inhibitory, sham) with pre- and post-fMRI scans

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in mentalizing task-related neural activity

4 weeks

Treatment Details

Interventions

• rTMS

Trial Overview The study tests if transcranial magnetic stimulation (TMS) at the right temporoparietal junction affects brain activity related to social understanding in people with autism, compared to non-autistic individuals.

Participant Groups

Group I: Typically Developing (TD): excitatory, then inhibitory, then sham rTMS Experimental Treatment 2 Interventions

Participants in this group will undergo fMRI pre- and post- rTMS. Each will receive an excitatory, inhibitory and sham rTMS to the right temporoparietal junction (TPJ) on mentalizing task-related (MTR) activity over 4 study visits.

Group II: ASD: excitatory, then inhibitory, then sham rTMS Experimental Treatment 2 Interventions

Participants in this group will undergo fMRI pre- and post- rTMS. Each will receive an excitatory, inhibitory and sham rTMS to the right temporoparietal junction (TPJ) on mentalizing task-related (MTR) activity over 4 study visits.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Findings from Research

In a study involving 13 adults with autism spectrum disorder (ASD) and major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) was found to be well tolerated, with mild side effects reported.

Participants experienced a significant reduction in depressive symptoms, with an average improvement of 13.5 points on the Hamilton rating scale for depression, and 40% achieved remission, suggesting rTMS may be an effective treatment for depression in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study. Gwynette, MF., Lowe, DW., Henneberry, EA., et al.[2023]

After 12 sessions of low-frequency rTMS applied to the dorsolateral prefrontal cortices, individuals with autism spectrum disorder (ASD) showed significant improvements in event-related potentials (N200 and P300) related to selective attention, indicating enhanced cognitive processing.

Participants also experienced a reduction in motor response errors, repetitive behaviors, and irritability, suggesting that rTMS may be a promising therapeutic tool for improving attention and behavioral symptoms in ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related Potential (ERP) Indices of Attention in Autism. Casanova, MF., Baruth, JM., El-Baz, A., et al.[2021]

In a study involving 11 participants with autism spectrum disorders (ASD), repetitive transcranial magnetic stimulation (rTMS) was found to enhance movement-related cortical potentials (MRCPs), indicating improved motor function.

Specifically, rTMS applied to the supplementary motor area (SMA) increased early MRCP components, while stimulation of the left primary motor cortex (M1) affected later components, suggesting that rTMS may influence cortical inhibitory processes to enhance motor activity in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. Enticott, PG., Rinehart, NJ., Tonge, BJ., et al.[2022]

In a study involving 32 autistic children with intellectual disabilities, 1 Hz repetitive transcranial magnetic stimulation (rTMS) was found to significantly improve brain activity, as indicated by changes in electroencephalogram (EEG) measures like recursive rate and deterministic features.

The experimental group receiving rTMS also showed notable improvements in behavior, as reflected in the Autism Behavior Checklist scores, suggesting that rTMS may be a beneficial intervention for enhancing both brain function and behavioral outcomes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of 1Hz repetitive transcranial magnetic stimulation on autism with intellectual disability: A pilot study. Kang, J., Zhang, Z., Wan, L., et al.[2022]

In a study involving 13 patients with autism and 13 controls, low frequency repetitive transcranial magnetic stimulation (rTMS) was applied twice a week for 3 weeks, leading to significant improvements in event-related potentials and behavioral measures.

The findings suggest that rTMS may enhance the inhibitory function of minicolumns in the brain, indicating its potential as a therapeutic intervention for autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on gamma frequency oscillations and event-related potentials during processing of illusory figures in autism. Sokhadze, EM., El-Baz, A., Baruth, J., et al.[2022]

Transcranial magnetic stimulation (TMS) has a reported overall adverse effect (AE) prevalence of 25% in individuals with autism spectrum disorder (ASD), with most AEs being mild and transient, such as headache (10%) and irritability (21%).

No specific risk factors related to ASD were identified that influenced the prevalence of AEs from TMS, suggesting that TMS may be a safe therapeutic option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Huashuang, Z., Yang, L., Chensheng, H., et al.[2022]

In a study involving 28 adults with autism spectrum disorder, deep repetitive transcranial magnetic stimulation (rTMS) targeting the dorsomedial prefrontal cortex showed a significant reduction in social relating symptoms compared to a sham treatment.

Participants receiving active rTMS also experienced decreased anxiety in social situations, suggesting that this technique may improve both social functioning and emotional responses in individuals with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. Enticott, PG., Fitzgibbon, BM., Kennedy, HA., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

Deep transcranial magnetic stimulation (dTMS) over the medial prefrontal cortex significantly reduced repetitive behaviors and improved emotional recognition and cognitive abilities in two young patients with high-functioning Autism after 5-6 weeks of treatment.

The treatment, which involved daily high-frequency (5 Hz) dTMS, appears to enhance sociability and communication skills, suggesting that dTMS may positively influence brain networks related to social cognition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced cognition and emotional recognition, and reduced obsessive compulsive symptoms in two adults with high-functioning autism as a result of deep Transcranial Magnetic Stimulation (dTMS): a case report. Avirame, K., Stehberg, J., Todder, D.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation (rTMS) Modulates Event-Related Potential (ERP) Indices of Attention in Autism. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation (rTMS) improves movement-related cortical potentials in autism spectrum disorders. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of 1Hz repetitive transcranial magnetic stimulation on autism with intellectual disability: A pilot study. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of low frequency repetitive transcranial magnetic stimulation (rTMS) on gamma frequency oscillations and event-related potentials during processing of illusory figures in autism. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A double-blind, randomized trial of deep repetitive transcranial magnetic stimulation (rTMS) for autism spectrum disorder. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Enhanced cognition and emotional recognition, and reduced obsessive compulsive symptoms in two adults with high-functioning autism as a result of deep Transcranial Magnetic Stimulation (dTMS): a case report. [2018]