Modulating Temporoparietal Junction Mentalizing-Related Activity in Autism Spectrum Disorder (ASD) Using Transcranial Magnetic Stimulation (TMS)

NCT ID: NCT06214065

Last Updated: 2025-04-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-03
• Study Completion Date: 2027-10-31

Brief Summary

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.

Detailed Description

All participants will be scheduled for four study sessions that include a baseline and three subsequent sessions that will each include two functional magnetic resonance imaging (fMRI) scans, one pre and one post an rTMS session.

During each fMRI scan, participants will be engaged in intersocial, competitive Domino task that involves mentalizing. rTMS manipulation, administered in a double-blind, counterbalanced fashion, includes one session each of excitatory (intermittent theta-burst stimulation, iTBS), inhibitory (continuous TBS, cTBS), and sham sequences. The rTMS will be guided with individualized electric-field modeling calculated from a structural MRI scan collected on the baseline session. This robust design is necessary to identify the optimal rTMS sequence to engage the right TPJ and the mentalizing network in ASD because firm conclusions about how best to modulate this network cannot be drawn from the few known published reports.

Investigators hypothesize that iTBS will result in increased, while cTBS in decreased MTR neural activity in the mentalizing network, with this being more pronounced in ASD, and sham resulting in no change. Understanding this mechanism will be the first and crucial step in validating rTMS of the right TPJ as a viable neural target to modulate neural circuit, and subsequently to modulate social-communication skills in ASD in future clinical studies. The significance of such a line of research should be considered in the context of the high prevalence of ASD and the dire need of developing effective interventions, especially for adults.

The three rTMS sessions will be compared within-subject and between-groups.

Conditions

Autism Spectrum Disorder

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

ASD: excitatory, then inhibitory, then sham rTMS

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 Type: EXPERIMENTAL

fMRI

Intervention Type: DIAGNOSTIC_TEST

fMRI will be performed pre- and post-rTMS

rTMS

Intervention Type: DEVICE

TMS procedures are scheduled during study sessions 2-4 between the two MRI scans on those days. Because rTMS induces neural changes that last about 1 hour, rTMS will be applied immediately before the second MRI scan on each day. Prior to the TMS visits, target coordinates and orientation vectors will be generated from the MRI data and the e-field models and loaded into Localite along with the participant's reconstructed T1 image. During the visits, the participant's head will be co-registered to the T1 using fiducial points at the Nasion and Tragi. TMS pulses will be delivered, using the Localite software to target and track the optimal orientation calculated with e-field modeling.

Typically Developing (TD): excitatory, then inhibitory, then sham rTMS

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 Type: EXPERIMENTAL

fMRI

Intervention Type: DIAGNOSTIC_TEST

fMRI will be performed pre- and post-rTMS

rTMS

Intervention Type: DEVICE

TMS procedures are scheduled during study sessions 2-4 between the two MRI scans on those days. Because rTMS induces neural changes that last about 1 hour, rTMS will be applied immediately before the second MRI scan on each day. Prior to the TMS visits, target coordinates and orientation vectors will be generated from the MRI data and the e-field models and loaded into Localite along with the participant's reconstructed T1 image. During the visits, the participant's head will be co-registered to the T1 using fiducial points at the Nasion and Tragi. TMS pulses will be delivered, using the Localite software to target and track the optimal orientation calculated with e-field modeling.

Interventions

fMRI

fMRI will be performed pre- and post-rTMS

Intervention Type: DIAGNOSTIC_TEST

rTMS

TMS procedures are scheduled during study sessions 2-4 between the two MRI scans on those days. Because rTMS induces neural changes that last about 1 hour, rTMS will be applied immediately before the second MRI scan on each day. Prior to the TMS visits, target coordinates and orientation vectors will be generated from the MRI data and the e-field models and loaded into Localite along with the participant's reconstructed T1 image. During the visits, the participant's head will be co-registered to the T1 using fiducial points at the Nasion and Tragi. TMS pulses will be delivered, using the Localite software to target and track the optimal orientation calculated with e-field modeling.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Estimated full-scale IQ>80
• Right handed
• Fluent in English
• Individual can cooperate with all study's procedures
• No history of neurological disorder (e.g. epilepsy) or neurosurgery
• No major medical condition (e.g. cancer, heart failure)
• No history of significant head injury
• No primary relatives with history of any neurological disorder with a potentially hereditary basis, including epilepsy or MS
• No current use of medications with psychotropic (e.g., benzodiazepines) or anti- or pro-convulsants
• No current substance use (determined by urine screen and breathalyzer in all visits)
• Negative urine pregnancy (women) test at time of MRI scans
• No MR contra-indications (e.g. in-body metal implant, severe claustrophobia)
• No previous participation in our lab in a study including the Domino fMRI task
• For ASD: Stable medication treatment 4 weeks prior to study enrollment
• For Control Group: No current or history of psychiatric disorders, other than simple phobia, and/or primary relatives with ASD

Exclusion Criteria

-

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vaughn Steele, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Michal Assaf, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Olin Neuropsychiatry Research Center (ONRC)

Hartford, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Michal Assaf, MD

Role: CONTACT

michal.assaf@hhchealth.org

860-545-7792

Vaughn R Steele, MD

Role: CONTACT

vaughn.steele@yale.edu

860-545-7855

Other Identifiers

R01MH132044

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Assaf 121223

Identifier Type: OTHER

Identifier Source: secondary_id

2000039667

Identifier Type: OTHER

Identifier Source: secondary_id

HHC-2023-0203

Identifier Type: -

Identifier Source: org_study_id