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NCT Number: NCT06484088

Study Brain Mechanisms of Frustration With Magnetoencephalography in Healthy Volunteers

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....

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Early Phase 1

Primary location

National Institutes of Health Clinical Center, Bethesda, Maryland, United States

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About this study

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:

  • 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;
  • 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

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

-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.

Treatment and study plan

Frustration task

Other

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.

Primary outcomes

  1. (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.

Study contacts

Contact information is provided by the study sponsor or research team.

Zheng Li, Ph.D.

CONTACT

[email protected]

(301) 594-2269

Sponsors and collaborators

Lead sponsor

National Institute of Mental Health (NIMH)

Nih

Registry information

Official study title

Characterizing the Brain Circuitry and Neural Activity Mediating Frustration

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Jul 3, 2024
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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