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 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

-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.

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 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 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.