Human Hippocampus Arbitrates Approach-Avoidance Conflict
Human Hippocampus Arbitrates Approach-Avoidance Conflict
复制标题
DOI：
10.1016/j.cub.2014.01.046
复制
发表时间：
2014-03-03
期刊：
影响因子：
9.2
通讯作者：
Dolan, Raymond J.
中科院分区：
文献类型：
--
作者：
Bach, Dominik R.;Guitart-Masip, Marc;Dolan, Raymond J.
人类焦虑的动物模型经常引发接近和回避之间的冲突 [1, 2]。其中，一个关键的行为分析包括被动避免潜在威胁和抑制，这两者都被认为是由腹侧海马体控制的[2-6]。将这些方法转化为临床环境的努力[7, 8]受到以下事实的阻碍：尚不清楚人类是否表现出类似的回避倾向，如果是的话，他们是否具有同源的神经生物学基础[9]。在这里，我们开发了一个范例来研究人类海马体在不同程度的潜在威胁下仲裁回避冲突中的作用。在四项实验中，受试者通过适应威胁水平的被动回避行为和行为抑制表现出类似的行为。使用功能磁共振成像（fMRI），我们观察到威胁水平涉及前海马体，即啮齿动物腹侧海马体的人类同源物[10]。对患有选择性海马损伤的患者进行测试，我们证明了海马体的因果作用，患者在所有威胁水平上都表现出被动回避行为和抑制行为减少。我们的数据提供了第一个类似于动物焦虑模型的人类接近-回避冲突分析。这些发现将啮齿动物和人类关于被动回避和行为抑制的研究联系起来，并为解决人类焦虑症的神经元基础提供了一个框架，我们的数据表明海马体在其中发挥着重要作用。
Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2-6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.