Recruiting

Fear Learning

Sponsor:

Washington University School of Medicine

Code:

NCT07800455

Conditions

Fear Extinction

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Direct intracranial electrical stimulation

Fear conditioning

Study Details

Brief summary:

The goal of this clinical trial is to understand how brain circuits involving the amygdala and prefrontal cortex contribute to fear learning and extinction. Fear extinction is the process by which a fear response decreases when a threat is no longer present. The study will include participants with epilepsy who are undergoing stereoelectroencephalography (SEEG) monitoring as part of their clinical care. The main questions this study aims to answer are: How do the amygdala and prefrontal cortex interact during fear learning and extinction? Do different parts and hemispheres of the amygdala have different roles in fear learning and extinction? How does electrical stimulation of the amygdala affect these brain circuits and fear extinction? Participants will complete tasks involving fear learning and extinction while researchers record brain activity from clinically implanted electrodes. Researchers will also use electrical stimulation via these electrodes to study how amygdala activity affects other brain regions and fear extinction.

Conditions

Fear Extinction

Study ID

NCT07800455

Start date

Sep 15, 2026

Status verified date

Aug, 2026

Completion date

Jul 31, 2032

Anticipated

Primary completion date

Jul 31, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. At least 18 years of age.
2. Able to understand the nature of the task.
3. Able to provide informed consent themselves or provide consent through their legally authorized representative.
4. Undergoing clinically indicated intracranial electrode implantation with coverage of at least one fear-related brain region, including the amygdala, hippocampus, cingulate cortex, insula, or prefrontal cortex.

Exclusion Criteria:

1. Under the age of 18.
2. Unable to understand the nature of the task.
3. Unable to provide informed consent themselves or provide consent through their legally authorized representative.
4. No clinically indicated intracranial electrode coverage in any fear-related brain region, including the amygdala, hippocampus, cingulate cortex, insula, or prefrontal cortex

Study Design

Enrollment

40 participants

Anticipated

Intervention Model

Single group

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Amygdala-prefrontal in Fear Extinction

Participants will undergo direct intracranial electrical stimulation and complete a Pavlovian fear conditioning and extinction task while neural activity is recorded through clinically implanted stereoelectroencephalography (SEEG) electrodes. Electrical stimulation, including single-pulse and/or high-frequency stimulation, will be delivered through the intracranial electrodes to investigate amygdala-prefrontal circuit dynamics. Participants may also receive theta-burst stimulation of the amygdala during extinction learning.

Interventions

Direct intracranial electrical stimulation

During a resting state and extinction learning phase, participants will receive electrical stimulation (single-pulse and/or high-frequency stimulation) through the intracranial electrodes while recording local field potentials from the neural networks. Direct electrical stimulation will be accomplished using FDA-approved equipment and stimulation protocols that are consistent with those used routinely for clinical purposes.

Fear conditioning

Participants will be involved in a Pavlovian fear conditioning/extinction experiment while recording local field potential signals from the neural networks. During the experiment, neutral stimuli will be paired with an aversive but not painful electric shock (via the surface skin of the hand/foot) or screeching sound.

Primary outcome measure

  • Broadband high-frequency power (70-170 Hz) in amygdala-prefrontal circuits [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Oscillatory power at the stimulation frequency during intracranial electrical stimulation [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Amplitude of cortico-cortical evoked potentials in amygdala-prefrontal circuits [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Theta/gamma band power in amygdala-prefrontal circuits [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Cross-frequency coupling in amygdala-prefrontal circuits [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Skin conductance response amplitude during fear conditioning and extinction [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Pupil diameter during fear conditioning and extinction [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Button press reaction time during fear conditioning and extinction [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]
  • Subjective unpleasantness rating during fear conditioning and extinction [ Time Frame: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay. ]

Central Contacts and Locations

Central contacts

Tao Xie, PhD

314-747-1443xiet@wustl.edu

Peter Brunner, PhD

314-747-1443pbrunner@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110-1010

Contacts

Juliana Amaral Passipieri, PhD

314-747-1443ajuliana@wustl.edu

Tao Xie, PhD

314-747-1443xiet@wustl.edu

Principal Investigator:

Tao Xie, PhD

More Information

Sponsor

Washington University School of Medicine

Last update posted

Sep 2, 2026

Last verified

Aug, 2026

Keywords

  • Fear extinction
  • Fear conditioning
  • Amygdala
  • Prefrontal cortex
  • Intracranial electrical stimulation
  • Fear learning
  • Stereoelectroencephalography
  • Neuromodulation

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-09-02.