Study Brain Mechanisms of Frustration With Magnetoencephalography in Healthy Volunteers

Early Phase 1

Recruiting

• Conditions: Irritability

• Registration Number: NCT06484088
• Lead Sponsor: National Institute of Mental Health (NIMH)

Brief Summary

Background:

Irritability can be defined as an unusually strong response to frustration; these responses may include severe temper outbursts and a constant grumpy mood. Irritability is a common symptom of many mental health disorders. Little is known about how the brain responds to frustration, and few treatments are available for this problem. Researchers want to know more about how the brain responds to frustration.

Objective:

To learn how the brain responds to frustration.

Eligibility:

Healthy adults aged 18 to 55 years. They must have been screened through studies 01-M-0254 or 17-M-0181.

Design:

Participants will have up to 3 study visits in 2 months. Each visit will last up to 4 hours.

Visit 1: Participants will be screened. They will have a physical exam. They will complete questionnaires about how often and how easily they get angry or grumpy. They will be trained to use a device that measures hand grip.

Visit 2: Participants will have a magnetic resonance imaging (MRI) scan. They will lie on a table that slides into a tube. Padding will hold their head still.

Visit 3: Participants will undergo magnetoencephalography (MEG). A cone with detectors will be lowered over their head while they are seated. The MEG will measure the magnetic fields in the participant s brain both while they are resting and while they are doing the frustration task. For the task, they will hold a grip device in each hand. They will use the devices to pick 1 of 2 doors on a computer screen. The task has 3 parts. The participant s face will be filmed during this task.

Detailed Description

STUDY DESCRIPTION:

Participants in this study will be healthy adults. This protocol uses a frustration induction task, magnetoencephalography (MEG), and brain magnetic resonance imaging (MRI), coupled with physical and self-report assessment of frustration, to study brain mechanisms underlying frustration in adults. This study is part of a cross-species project; hence, hypotheses are based on neural mechanisms of frustration identified in mice.

OBJECTIVES:

To use a frustration induction task, MEG, and brain MRI, coupled with physical and self-report assessment of frustration, to measure how frustration alters synchronized neural activities and physical activities. Specifically, we will identify brain circuits and neural oscillations that potentially underly the emotional and behavioral consequences of frustration and characteristic changes in grip force, pupil/cornea size, and facial expressions that can be used as objective measurements of frustration.

ENDPOINTS:

1. The power of neural oscillations in the cortical-basal gangliathalamic circuit, which we hypothesize will be altered by frustration comparing pre and post-frustration resting states, and increased more by unexpected reward omission than reward attainment;

2. Coherence of neural oscillations in the above-mentioned circuit, which we hypothesize will be increased in the beta band by unexpected reward omission but not by expected reward omission, and that this decrease will accumulate with the number of frustration episodes; (3) Frustration rating by self-report, facial expression, pupil/cornea size, and the duration and strength of gripping, which we hypothesize will be higher after unexpected reward omission than after expected reward omission

Study Timeline

• Study First Submitted: 2024-06-29
• Study First Submitted QC: 2024-07-01
• Study First Posted: 2024-07-03
• Study Start: 2025-02-21
• Status Verified: 2025-09-03
• Last Update Submitted: 2025-09-04
• Last Update Posted: 2025-09-05
• Primary Completion: 2027-08-31
• Study Completion: 2027-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
(1) The power of neural oscillations in the cortical-basal ganglia-thalamic circuit; (2) Coherence of neural oscillations in this circuit; (3) Frustration rating by self-report, facial expression, and the duration and strength of gripping.	The measurements will be taken during the MEG/frustration task session.	MEG recording is acquired during the frustration task. 3-6 minutes of resting-state recording is acquired before, between, and after each block of the frustration task. Feelings of frustration and unhappiness were assessed after each run using 9-point Likert scales. Frustration assessment takes place before and after the task and between each block within the task. The strength and duration of gripping the press device during the task is recorded for all trials.

Trial Locations

Locations (2)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States

Texas A&M University; 🇺🇸 College Station, Texas, United States