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Amygdala-Prefrontal in Fear Extinction

2026년 8월 28일 업데이트: Washington University School of Medicine

Causal Dynamics of Human Amygdala-Prefrontal Circuits During Fear Extinction Learning

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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

The ability to reduce fear responses through extinction when threats are no longer present is essential for mental health. Deficits in extinction underlie fear-related disorders such as post-traumatic stress disorder (PTSD). A critical gap remains in understanding the neural mechanisms underlying fear extinction, which poses a major barrier to developing more effective therapeutic interventions. The amygdala (AMY)-prefrontal circuits are critical in fear extinction. In animal models, the lateral nucleus of the amygdala (LA) receives sensory inputs and initiates fear learning, while the basal nucleus of the amygdala (BA) integrates regulatory inputs from the ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC) for appropriate fear response. However, due to species-specific differences between animal and human neurobiology, the nucleus-specific contributions of the amygdala and their interactions with the vmPFC and dACC in human fear extinction and regulation remain poorly understood. Clinically indicated stereoelectroencephalography (SEEG) electrodes, which allow direct recording and stimulation of amygdala-prefrontal circuits, provide a unique opportunity to address this gap. The objective of this study is to determine the causal dynamics of amygdala-prefrontal circuits involved in fear extinction learning in participants with epilepsy undergoing SEEG monitoring. The study will address three aims: (1) Determine the intrinsic and stimulation-induced dynamics of human amygdala-prefrontal circuits. The study will characterize cause pathways and circuit-level interactions in amygdala-vmPFC-dACC circuits using intracranial recordings and electrical stimulation. (2) Characterize nucleus-specific and hemispherical lateralized dynamics of amygdala-prefrontal circuits during fear extinction. The study will examine the neural dynamics of the LA, BA, and left and right amygdala-prefrontal circuits during fear extinction and regulation. (3) Determine the effects of theta-burst stimulation of amygdala nuclei on fear extinction. Theta-burst stimulation will be applied to the LA and BA during extinction learning to examine how targeted stimulation modulates fear-related neural circuits and behavior.

연구 유형

중재적

등록 (추정된)

40

단계

  • 해당 없음

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Tao Xie, PhD
  • 전화번호: 314-747-1443
  • 이메일: xiet@wustl.edu

연구 연락처 백업

연구 장소

    • Missouri
      • St Louis, Missouri, 미국, 63110-1010
        • 모병
        • Washington University School of Medicine
        • 연락하다:
        • 연락하다:
        • 수석 연구원:
          • Tao Xie, PhD

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 기초 과학
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
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.
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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Broadband high-frequency power (70-170 Hz) in amygdala-prefrontal circuits
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
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.
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
기간: 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 will be quantified from local field potentials recorded through clinically implanted stereoelectroencephalography (SEEG) electrodes in the amygdala and prefrontal cortex. Power at the stimulation frequency will be assessed during intracranial electrical stimulation to quantify stimulation-induced oscillatory entrainment within amygdala-prefrontal circuits. For theta-burst stimulation, theta-band activity (4-8 Hz) will be assessed.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Cortico-cortical evoked potential (CCEP) amplitude will be quantified from local field potentials recorded through clinically implanted stereoelectroencephalography (SEEG) electrodes following single-pulse intracranial electrical stimulation. CCEP amplitude will be used to assess effective connectivity between the amygdala and prefrontal cortex.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Theta (4-8 Hz) and gamma (30-50 Hz) band power will be quantified from local field potentials recorded through clinically implanted stereoelectroencephalography (SEEG) electrodes in the amygdala and prefrontal cortex. Theta/gamma-band power will be assessed during fear conditioning and extinction to characterize oscillatory neural activity within amygdala-prefrontal circuits.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Cross-frequency coupling will be quantified from local field potentials recorded through clinically implanted stereoelectroencephalography (SEEG) electrodes in the amygdala and prefrontal cortex. Coupling between neural activity across different frequency bands, including phase-amplitude coupling between lower-frequency oscillations and high-frequency activity, will be assessed during resting state and fear processing to characterize cross-frequency neural interactions within amygdala-prefrontal circuits.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Skin conductance response (SCR) amplitude will be quantified during fear conditioning and extinction to assess autonomic responses to conditioned stimuli.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Pupil diameter will be quantified from eye-tracking recordings during fear conditioning and extinction to assess autonomic responses to conditioned stimuli.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Button press reaction time will be quantified during fear conditioning and extinction to assess behavioral responses to conditioned stimuli.
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
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Participants will rate the unpleasantness of the conditioned stimuli during fear conditioning and extinction. Ratings will be used to quantify subjective emotional responses to the conditioned stimuli.
During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.

2차 결과 측정

결과 측정
측정값 설명
기간
Heart rate during fear conditioning and extinction
기간: During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.
Heart rate will be quantified during fear conditioning and extinction to assess autonomic responses to conditioned stimuli.
During research sessions, up to 2 hours per day for up to 4 days during the participant's hospital stay.

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

협력자

수사관

  • 수석 연구원: Tao Xie, PhD, Washington University School of Medicine

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 9월 15일

기본 완료 (추정된)

2031년 7월 31일

연구 완료 (추정된)

2032년 7월 31일

연구 등록 날짜

최초 제출

2026년 8월 18일

QC 기준을 충족하는 최초 제출

2026년 8월 28일

처음 게시됨 (실제)

2026년 9월 2일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 2일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 8월 28일

마지막으로 확인됨

2026년 8월 1일

추가 정보

이 연구와 관련된 용어

기타 연구 ID 번호

  • 202507143
  • K99MH144521 (미국 NIH 보조금/계약)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .