Irritability, Mental Health
Conditions
Brief summary
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.
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.
Interventions
DEVICErepetitive 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_TESTfMRI
fMRI will be performed pre- and post rTMS
Sponsors
Yale University
Yale Center for Brain and Mind Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 25 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frontostriatal connectivity | Day 1-3 | Frontostriatal connectivity easured using fMRI during a frustration task. The unit of measure is degrees of functional connectivity. |
| Grip force (an index of motor activity) | Day 1-3 | Grip force measured using a dynamometer during a frustration task. The unit of measure is pounds of force. |
| Self-reported frustration and unhappiness | Day 1-3 | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORVaughn R Steele, PhD
Yale University
Outcome results
None listed