Study Brain Mechanisms of Frustration With Magnetoencephalography in Healthy Volunteers

Official title

Characterizing the Brain Circuitry and Neural Activity Mediating Frustration

Overview

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

Interventions

• 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.

Primary outcome measures

• (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.]

Eligibility criteria

-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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 2 centers

• National Institutes of Health Clinical Center — Bethesda
• Texas A&M University — College Station

Publications

• Beauchaine TP, Tackett JL. Irritability as a Transdiagnostic Vulnerability Trait:Current Issues and Future Directions. Behav Ther. 2020 Mar;51(2):350-364. doi: 10.1016/j.beth.2019.10.009. Epub 2019 Nov 27. PMID 32138943
• Brotman MA, Kircanski K, Leibenluft E. Irritability in Children and Adolescents. Annu Rev Clin Psychol. 2017 May 8;13:317-341. doi: 10.1146/annurev-clinpsy-032816-044941. PMID 28482689
• Eshel N, Leibenluft E. New Frontiers in Irritability Research-From Cradle to Grave and Bench to Bedside. JAMA Psychiatry. 2020 Mar 1;77(3):227-228. doi: 10.1001/jamapsychiatry.2019.3686. No abstract available. PMID 31799997
• Linke JO, Haller SP, Xu EP, Nguyen LT, Chue AE, Botz-Zapp C, Revzina O, Perlstein S, Ross AJ, Tseng WL, Shaw P, Brotman MA, Pine DS, Gotts SJ, Leibenluft E, Kircanski K. Persistent Frustration-Induced Reconfigurations of Brain Networks Predict Individual Differences in Irritability. J Am Acad Child Adolesc Psychiatry. 2023 Jun;62(6):684-695. doi: 10.1016/j.jaac.2022.11.009. Epub 2022 Dec 21. PMID 36563874
• Tseng WL, Deveney CM, Stoddard J, Kircanski K, Frackman AE, Yi JY, Hsu D, Moroney E, Machlin L, Donahue L, Roule A, Perhamus G, Reynolds RC, Roberson-Nay R, Hettema JM, Towbin KE, Stringaris A, Pine DS, Brotman MA, Leibenluft E. Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths. Am J Psychiatry. 2019 Jan 1;176(1):67-76. doi: 10.1176/app PMID 30336704
• AMSEL A. The role of frustrative nonreward in noncontinuous reward situations. Psychol Bull. 1958 Mar;55(2):102-19. doi: 10.1037/h0043125. No abstract available. PMID 13527595
• Naik AA, Ma X, Munyeshyaka M, Leibenluft E, Li Z. A New Behavioral Paradigm for Frustrative Non-reward Reveals a Global Change in Brain Networks by Frustration. bioRxiv [Preprint]. 2023 Jun 6:2023.02.28.530477. doi: 10.1101/2023.02.28.530477. PMID 36909498
• Naik AA, Ma X, Munyeshyaka M, Leibenluft E, Li Z. A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice. Biol Psychiatry Glob Open Sci. 2023 Nov 17;4(1):31-38. doi: 10.1016/j.bpsgos.2023.09.007. eCollection 2024 Jan. PMID 38045768

Identifiers

NCT: NCT06484088 · 10002073 · 002073-M

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗