Amygdala-Prefrontal in Fear Extinction

ConditionFear Extinction

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

SponsorWashington University School of Medicine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

At least 18 years of age.

Able to understand the nature of the task.

Able to provide informed consent themselves or provide consent through their legally authorized representative.

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.

Disqualifiers

Under the age of 18.

Unable to understand the nature of the task.

Unable to provide informed consent themselves or provide consent through their legally authorized representative.

No clinically indicated intracranial electrode coverage in any fear-related brain region, including the amygdala, hippocampus, cingulate cortex, insula, or prefrontal cortex

Trial design

Design model

Single group

Treatments tested in this trial

Direct intracranial electrical stimulation
Other intervention
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
Behavioral
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.

Treatment groups

40 Participants

are divided into 1 treatment group

Group A: Amygdala-prefrontal in Fear ExtinctionExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Broadband high-frequency power (70-170 Hz) in amygdala-prefrontal circuits

Broadband high-frequency power (70-170 Hz) will be quantified from local field potentials recorded through clinically implanted stereoelectroencephalography (SEEG) electrodes in the amygdala and prefrontal cortex. Broadband high-frequency power will be assessed during fear processing and during intracranial electrical stimulation to characterize local neural activity within amygdala-prefrontal circuits. For stimulation recordings, stimulation artifacts will be removed using appropriate artifact-removal methods, for example, MPARRM (matching pursuit-based artifact reconstruction and removal method) for single-pulse stimulation and LIBRA (linear baseline-integrated removal of artifacts) for high-frequency stimulation.

Time frame