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

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.

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)