Study Brain Mechanisms of Frustration With Magnetoencephalography in Healthy Volunteers

April 28, 2026 updated by: National Institute of Mental Health (NIMH)

Characterizing the Brain Circuitry and Neural Activity Mediating Frustration

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

90

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
        • Contact:
          • Office of Patient Recruitment (OPR)
          • Phone Number: TTY dial 711 800-411-1222
          • Email: ccopr@nih.gov
    • Texas
      • College Station, Texas, United States, 77843
        • Not yet recruiting
        • Texas A&M University
        • Contact:
          • Yuming Lei, PhD
          • Phone Number: 979-845-3211

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

-INCLUSION CRITERIA:

This study will include adult healthy volunteers.

  • Age: 18-55
  • Consent: can give consent

  • Speak and read English

    --The instruments have not been validated in other languages.

  • At the NIH site, previously screened through other NIH protocols such as protocol 01-M-0254, 17-M-0181, and 93-M-0170 and determined eligible as healthy volunteers.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this

study:

-Any serious medical condition

  • History, physical exam, or laboratory testing including drug abuse screen.

    -Prescription and over-the-counter medications and dietary supplements with psychoactive properties (e.g., St. John's Wort, Melatonin, Valerian)

    -Any condition that interferes with MRI or MEG**

  • History

    -Any current psychiatric diagnosis

  • SCID-V, clinical assessment, or history.

    -Pregnancy

  • Pregnancy testing will be done before all MRIs.

    -People who work on night shifts

  • History

    -Drug use

  • Subjects with drug use or positive drug screen more than two years ago are eligible for participation.

    -Need to wear eye glasses to work with computers*

  • History

    -Need to wear contact lenses to work with computers**,***

  • History

    -Dental retainer**

  • Subjects wearing removable dental retainers are eligible for participation

    • Eye glasses create artifacts in MEG and their rigid shape does not fit well in the MEG scanner. The MEG core has plastic optometry lenses that can be placed in paper frames. However, the paper frames need to be secured with tape which makes wearing them very uncomfortable, potentially promoting negative emotion and reducing the reliability of facial expression analysis.

      • Only applies to the NIH site.

        • Contact lenses create artifacts that interfere with eye-tracking.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Frustration task
The experimental manipulation for this study is the frustration task. The frustration task is designed to elicit the emotional state of frustrative non-reward (FNR). During the task, participants are asked to use button press (left or right) to alternately press one of the two doors displayed on the monitor. The task has two non-frustration blocks (Block 1 and 2) and one frustration block (Block 3). During the non-frustration blocks, participants earn money for correct press on a fixed schedule. During the frustrative block, participants will not always receive reward for correct press.
Other: Frustration task
The experimental manipulation for this study is the frustration task. The frustration task is designed to elicit the emotional state of frustrative non-reward (FNR). During the task, participants are asked to use button press (left or right) to alternately press one of the two doors displayed on the monitor. The task has two non-frustration blocks (Block 1 and 2) and one frustration block (Block 3). During the non-frustration blocks, participants earn money for correct press on a fixed schedule. During the frustrative block, participants will not always receive reward for correct press.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
(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.
Time Frame: 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.
The measurements will be taken during the MEG/frustration task session.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Zheng Li, Ph.D., National Institute of Mental Health (NIMH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2025

Primary Completion (Estimated)

August 31, 2027

Study Completion (Estimated)

August 31, 2027

Study Registration Dates

First Submitted

June 29, 2024

First Submitted That Met QC Criteria

July 1, 2024

First Posted (Actual)

July 3, 2024

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 16, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 10002073
  • 002073-M

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD that underlies results in a publication will be made available upon requested by other researchers. If participants are co-enrolled in another NIH protocol, then data collected in either study may be shared with and used for research in either study.

IPD Sharing Time Frame

IPD that under results in a publication may be requested by other researchers when the publication is online or in print or by the end of the project/protocol, whichever comes first.

IPD Sharing Access Criteria

IPD that under results in a publication will be made public through NIH-supported scientific data repositories. Access criteria are defined by the repositories and not limited by analysis type.

IPD Sharing Supporting Information Type

  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Irritability

Clinical Trials on Frustration task

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe