Targeting Fronto-Striatal Neural Circuitry Using Repetitive Transcranial Magnetic Stimulation to Reduce Irritability

This pilor study will use repetitive Transcranial Magnetic Stimulation (rTMS) as a noninvasive circuit-based neural modulation to test frontostriatal circuitry as a potential target to reduce irritability.

Study Overview

• Status: Active, not recruiting
• Conditions: Irritability; Mental Health
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation (rTMS); Diagnostic test: fMRI

Detailed Description

Aim 1: To establish frontostriatal (dACC, dlPFC, striatum) circuitry as the neural circuitry mediating frustration.

Aim 2: To modulate the neural circuitry of frustration and evaluate the neural, behavioral, and affective responses.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• able to give informed consent in English
• elevated levels of irritability, defined as scoring ≥5 on the Affective Reactivity Index (ARI)
• Absence of cognitive impairment. Must have an IQ equivalent of ≥ 70 on the WASI
• Absence of MRI or TMS contraindications

Exclusion Criteria:

• History of any neurological disorder that would increase seizure risk from rTMS such as stroke, brain lesions, previous neurosurgery, any history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than one month.
• First-degree family history of any neurological disorder with a potentially hereditary basis, including epilepsy or multiple sclerosis.
• Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps or sensors, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object in the body that precludes rTMS or MRI administration.
• Current use of any investigational drug or of anti or pro-convulsive action.
• Use of benzodiazepines.
• Lifetime history of schizophrenia, bipolar disorder, mania, autism spectrum disorder, intellectual disability, hypomania, or post-traumatic stress disorder.
• History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack.
• Participation in any TMS session less than 2 weeks prior to admission. (No TMS exposure for treatment purposes in the last 6 months.)
• History or current substance use disorder, excluding cannabis use disorder.
• Major medical illnesses.
• An acute risk of hurting themselves or others.
• Pregnant or lactating women.
• Participant-reported history of severe claustrophobia.
• Excessive weight beyond the MRI limit (> 450 lbs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: rTMS participants; Participants will be asked to complete a 3-day within-participant active and sham rTMS crossover study and perform tasks pre and post sessions while fMRI data is collected. Each will receive an active and sham rTMS.

Device: repetitive transcranial magnetic stimulation (rTMS); Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to cause electric current at a specific area of the brain through electromagnetic induction. To administer TMS, a stimulator equipped with a figure-8 coil will be used. Two separate coils will be used that are similar in appearance and acoustic properties. One active, unblinded, coil will be used to determine resting motor threshold (RMT) and deliver pulses for the recruitment curves; the other coil will be used to deliver rTMS. rTMS stimulation will be targeted to l-dlPFC.; Diagnostic test: fMRI; fMRI will be performed pre- and post rTMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frontostriatal connectivity	Frontostriatal connectivity easured using fMRI during a frustration task. The unit of measure is degrees of functional connectivity.	Day 1-3
Grip force (an index of motor activity)	Grip force measured using a dynamometer during a frustration task. The unit of measure is pounds of force.	Day 1-3
Self-reported frustration and unhappiness	Self-reported frustration and unhappiness measured using self-rated Likert scales from 1 to 9 during a frustration task. Total score range 1-9 with higher scores indicating more frustration and unhappiness.	Day 1-3

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Yale Center for Brain and Mind Health
• Investigators: Principal Investigator: Vaughn R Steele, PhD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: June 24, 2026
• First Submitted That Met QC Criteria: June 24, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 24, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Personal Satisfaction; Psychological Well-Being; Therapeutics; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Field Therapy; Magnetic Resonance Imaging; Transcranial Magnetic Stimulation
• Other Study ID Numbers: HHC-2024-0180

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes