Amygdala-Prefrontal in Fear Extinction
2026年8月28日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (推定)
40
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Tao Xie, PhD
- 電話番号：314-747-1443
- メール：xiet@wustl.edu
研究連絡先のバックアップ
- 名前：Peter Brunner, PhD
- 電話番号：314-747-1443
- メール：pbrunner@wustl.edu
研究場所
-
-
Missouri
-
St Louis、Missouri、アメリカ、63110-1010
- 募集
- Washington University School of Medicine
-
コンタクト：
- Juliana Amaral Passipieri, PhD
- 電話番号：314-747-1443
- メール：ajuliana@wustl.edu
-
コンタクト：
- Tao Xie, PhD
- 電話番号：314-747-1443
- メール：xiet@wustl.edu
-
主任研究者：
- Tao Xie, PhD
-
-
参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
いいえ
説明
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：基礎科学
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Broadband high-frequency power (70-170 Hz) in amygdala-prefrontal circuits
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Heart rate during fear conditioning and extinction
時間枠：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.
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Tao Xie, PhD、Washington University School of Medicine
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- Xie T, Foutz TJ, Adamek M, Swift JR, Inman CS, Manns JR, Leuthardt EC, Willie JT, Brunner P. Single-pulse electrical stimulation artifact removal using the novel matching pursuit-based artifact reconstruction and removal method (MPARRM). J Neural Eng. 2023 Dec 27;20(6):066036. doi: 10.1088/1741-2552/ad1385.
- Xie T, van Rooij SJH, Inman CS, Wang S, Brunner P, Willie JT. The case for hemispheric lateralization of the human amygdala in fear processing. Mol Psychiatry. 2025 May;30(5):2252-2259. doi: 10.1038/s41380-025-02940-2. Epub 2025 Feb 27.
- Xie T, van Rooij SJH, Sun S, Bryson NK, Demarest P, Park H, Maccotta L, Wang S, Brunner P, Willie JT. Right amygdala ablation reduces maladaptive negative interpretation bias and symptoms in a patient with post-traumatic stress disorder. Nat Commun. 2026 Jun 22;17(1):7868. doi: 10.1038/s41467-026-74099-5.
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年9月15日
一次修了 (推定)
2031年7月31日
研究の完了 (推定)
2032年7月31日
試験登録日
最初に提出
2026年8月18日
QC基準を満たした最初の提出物
2026年8月28日
最初の投稿 (実際)
2026年9月2日
学習記録の更新
投稿された最後の更新 (実際)
2026年9月2日
QC基準を満たした最後の更新が送信されました
2026年8月28日
最終確認日
2026年8月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。