IrritabilityEarly Phase 1NCT06484088
Study Brain Mechanisms of Frustration With Magnetoencephalography in Healthy Volunteers
A Early Phase 1 study testing Frustration task in people with Irritability, run by National Institute of Mental Health (NIMH) at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Irritability
- What is being tested?
- Frustration task
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Feb 2025to 31 Aug 2027
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 24Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
Zheng Li, Ph.D., (301) 594-2269, lizheng2@mail.nih.gov
- Not yet recruiting
Texas A&M University
College Station, Texas, 77843
Yuming Lei, PhD, 979-845-3211
About this study
Official title: 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.
Read more
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.
Read the 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:
- 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
- Conditions
- Irritability
- Being tested
- Frustration task
- Keywords
- Healthy volunteers, Frustration, Magnetoencephalography
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Frustration taskOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Frustration task | Experimental | 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. Receives: Other: Frustration task |
What is being measured
The primary outcome is the main question the study is designed to answer.
(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.
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.
Measured: The measurements will be taken during the MEG/frustration task session.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2024
- Study start21 Feb 2025
- Primary completion31 Aug 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (38)Papers the sponsor has linked to this study.
- Other trials for IrritabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Zheng Li, Ph.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06484088
- Sponsor's protocol ID
- 10002073
- Other IDs
- 002073-M
- Status last verified
- 21 Oct 2026
- First submitted
- 29 Jun 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
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.
PubMed 32138943Brotman 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.
PubMed 28482689Eshel 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.
PubMed 31799997Linke 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.
PubMed 36563874Tseng 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/appi.ajp.2018.18040491. Epub 2018 Oct 19.
PubMed 30336704AMSEL 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.
PubMed 13527595Naik 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.
PubMed 36909498Naik 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.
PubMed 38045768Vrba J, Robinson SE. Signal processing in magnetoencephalography. Methods. 2001 Oct;25(2):249-71. doi: 10.1006/meth.2001.1238.
PubMed 11812209Pizzo F, Roehri N, Medina Villalon S, Trebuchon A, Chen S, Lagarde S, Carron R, Gavaret M, Giusiano B, McGonigal A, Bartolomei F, Badier JM, Benar CG. Deep brain activities can be detected with magnetoencephalography. Nat Commun. 2019 Feb 27;10(1):971. doi: 10.1038/s41467-019-08665-5.
PubMed 30814498Salvadore G, Cornwell BR, Sambataro F, Latov D, Colon-Rosario V, Carver F, Holroyd T, DiazGranados N, Machado-Vieira R, Grillon C, Drevets WC, Zarate CA Jr. Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine. Neuropsychopharmacology. 2010 Jun;35(7):1415-22. doi: 10.1038/npp.2010.24. Epub 2010 Mar 10.
PubMed 20393460Cornwell BR, Carver FW, Coppola R, Johnson L, Alvarez R, Grillon C. Evoked amygdala responses to negative faces revealed by adaptive MEG beamformers. Brain Res. 2008 Dec 9;1244:103-12. doi: 10.1016/j.brainres.2008.09.068. Epub 2008 Oct 7.
PubMed 18930036Carlson GA, Singh MK. Emotion Dysregulation and Outbursts in Children and Adolescents: Part I. Child Adolesc Psychiatr Clin N Am. 2021 Apr;30(2):xiii-xvi. doi: 10.1016/j.chc.2020.10.014. Epub 2021 Feb 15. No abstract available.
PubMed 33743952Singh MK, Carlson GA. Emotion Dysregulation in Children and Adolescents: Part II. Child Adolesc Psychiatr Clin N Am. 2021 Jul;30(3):xiii-xiv. doi: 10.1016/j.chc.2021.05.002. No abstract available.
PubMed 34053694Tseng WL, Naim R, Chue A, Shaughnessy S, Meigs J, Pine DS, Leibenluft E, Kircanski K, Brotman MA. Network analysis of ecological momentary assessment identifies frustration as a central node in irritability. J Child Psychol Psychiatry. 2023 Aug;64(8):1212-1221. doi: 10.1111/jcpp.13794. Epub 2023 Mar 28.
PubMed 36977629