Harrison Ben J, Fullana Miquel A, Soriano-Mas Carles, Via Esther, Pujol Jesus, Martínez-Zalacaín Ignacio, Tinoco-Gonzalez Daniella, Davey Christopher G, López-Solà Marina, Pérez Sola Victor, Menchón José M, Cardoner Narcís
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Victoria, Australia.
Institute of Neuropsychiatry and Addictions, Hospital Del Mar, CIBERSAM G21, Barcelona, Spain.
Hum Brain Mapp. 2015 Oct;36(10):3950-8. doi: 10.1002/hbm.22889. Epub 2015 Jul 6.
Advances in the neuroscientific understanding of bodily autonomic awareness, or interoception, have led to the hypothesis that human trait anxiety sensitivity (AS)-the fear of bodily autonomic arousal-is primarily mediated by the anterior insular cortex. Despite broad appeal, few experimental studies have comprehensively addressed this hypothesis. We recruited 55 individuals exhibiting a range of AS and assessed them with functional magnetic resonance imaging (fMRI) during aversive fear conditioning. For each participant, three primary measures of interest were derived: a trait Anxiety Sensitivity Index score; an in-scanner rating of elevated bodily anxiety sensations during fear conditioning; and a corresponding estimate of whole-brain functional activation to the conditioned versus nonconditioned stimuli. Using a voxel-wise mediation analysis framework, we formally tested for 'neural mediators' of the predicted association between trait AS score and in-scanner anxiety sensations during fear conditioning. Contrary to the anterior insular hypothesis, no evidence of significant mediation was observed for this brain region, which was instead linked to perceived anxiety sensations independently from AS. Evidence for significant mediation was obtained for the dorsal anterior cingulate cortex-a finding that we argue is more consistent with the hypothesized role of human cingulofrontal cortex in conscious threat appraisal processes, including threat-overestimation. This study offers an important neurobiological validation of the AS construct and identifies a specific neural substrate that may underlie high AS clinical phenotypes, including but not limited to panic disorder.
对身体自主意识（即内感受）的神经科学理解取得的进展，引发了这样一种假说：人类特质焦虑敏感性（AS）——对身体自主唤醒的恐惧——主要由前岛叶皮层介导。尽管该假说颇具吸引力，但很少有实验研究全面探讨过这一假说。我们招募了55名表现出不同程度AS的个体，并在厌恶恐惧条件反射过程中用功能磁共振成像（fMRI）对他们进行评估。对于每位参与者，得出了三项主要的感兴趣指标：特质焦虑敏感性指数得分；恐惧条件反射过程中扫描仪内对身体焦虑感觉增强的评分；以及对条件刺激与非条件刺激的全脑功能激活的相应估计值。使用基于体素的中介分析框架，我们正式检验了在恐惧条件反射过程中，特质AS得分与扫描仪内焦虑感觉之间预测关联的“神经中介”。与前岛叶假说相反，未观察到该脑区有显著中介作用的证据，相反，该脑区与感知到的焦虑感觉相关，且与AS无关。背侧前扣带回皮层存在显著中介作用的证据——我们认为这一发现更符合人类扣带前皮层在包括威胁高估在内的有意识威胁评估过程中的假定作用。这项研究为AS结构提供了重要的神经生物学验证，并确定了一个特定的神经基质，它可能是高AS临床表型的基础，包括但不限于惊恐障碍。
