Andres Elena, Meyer Benjamin, Yuen Kenneth S L, Kalisch Raffael
Leibniz Institute for Resilience Research (LIR), Mainz, Germany.
Donders Centre for Cognitive Neuroimaging, Radboud University, Nijmegen, The Netherlands.
Curr Top Behav Neurosci. 2025 Jan 3. doi: 10.1007/7854_2024_555.
The elucidation of the functional neuroanatomy of human fear, or threat, extinction has started in the 2000s by a series of enthusiastically greeted functional magnetic resonance imaging (fMRI) studies that were able to translate findings from rodent research about an involvement of the ventromedial prefrontal cortex (vmPFC) and the hippocampus in fear extinction into human models. Enthusiasm has been painfully dampened by a meta-analysis of human fMRI studies by Fullana and colleagues in 2018 who showed that activation in these areas is inconsistent, sending shock waves through the extinction research community. The present review guides readers from the field (as well as non-specialist readers desiring safe knowledge about human extinction mechanisms) during a series of exposures with corrective information. New information about extinction-related brain activation not considered by Fullana et al. will also be presented. After completion of this exposure-based fear reduction program, readers will trust that the reward learning system, the cerebellum, the vmPFC, the hippocampus, and a wider brain network are involved in human fear extinction, along with the neurotransmitters dopamine and noradrenaline. Specific elements of our exposure program include exploitation of the temporal dynamics of extinction, of the spatial heterogeneity of extinction-related brain activation, of functional connectivity methods, and of large sample sizes. Implications of insights from studies in healthy humans for the understanding and treatment of anxiety-related disorders are discussed.
对人类恐惧或威胁消退的功能性神经解剖学的阐释始于21世纪，一系列备受欢迎的功能磁共振成像（fMRI）研究将啮齿动物研究中关于腹内侧前额叶皮层（vmPFC）和海马体参与恐惧消退的发现转化为人类模型。然而，2018年富拉纳及其同事对人类fMRI研究的一项荟萃分析令人痛苦地浇灭了这种热情，该分析表明这些区域的激活并不一致，这在消退研究领域引起了轩然大波。本综述在一系列包含纠正信息的阐述过程中引导该领域的读者（以及渴望安全了解人类消退机制的非专业读者）。还将呈现富拉纳等人未考虑到的与消退相关的大脑激活的新信息。在完成这个基于暴露的恐惧减轻计划后，读者将相信奖赏学习系统、小脑、vmPFC、海马体以及更广泛的脑网络，连同神经递质多巴胺和去甲肾上腺素，都参与了人类恐惧的消退。我们的暴露计划的具体要素包括利用消退的时间动态、消退相关大脑激活的空间异质性、功能连接方法以及大样本量。讨论了健康人类研究中的见解对理解和治疗焦虑相关障碍的意义。
