Kalin N H, Shelton S E, Davidson R J, Kelley A E
Departments of Psychiatry and Psychology, University of Wisconsin, Madison, Wisconsin 53719, USA.
J Neurosci. 2001 Mar 15;21(6):2067-74. doi: 10.1523/JNEUROSCI.21-06-02067.2001.
Temperamentally anxious individuals can be identified in childhood and are at risk to develop anxiety and depressive disorders. In addition, these individuals tend to have extreme asymmetric right prefrontal brain activity. Although common and clinically important, little is known about the pathophysiology of anxious temperament. Regardless, indirect evidence from rodent studies and difficult to interpret primate studies is used to support the hypothesis that the amygdala plays a central role. In previous studies using rhesus monkeys, we characterized an anxious temperament endophenotype that is associated with excessive anxiety and fear-related responses and increased electrical activity in right frontal brain regions. To examine the role of the amygdala in mediating this endophenotype and other fearful responses, we prepared monkeys with selective fiber sparing ibotenic acid lesions of the amygdala. Unconditioned trait-like anxiety-fear responses remained intact in monkeys with >95% bilateral amygdala destruction. In addition, the lesions did not affect EEG frontal asymmetry. However, acute unconditioned fear responses, such as those elicited by exposure to a snake and to an unfamiliar threatening conspecific were blunted in monkeys with >70% lesions. These findings demonstrate that the primate amygdala is involved in mediating some acute unconditioned fear responses but challenge the notion that the amygdala is the key structure underlying the dispositional behavioral and physiological characteristics of anxious temperament.
气质性焦虑的个体在童年期即可被识别,且有发展为焦虑症和抑郁症的风险。此外,这些个体往往具有极端不对称的右侧前额叶脑活动。尽管常见且具有临床重要性,但对于焦虑气质的病理生理学知之甚少。无论如何,来自啮齿动物研究和难以解释的灵长类动物研究的间接证据被用来支持杏仁核起核心作用的假说。在之前使用恒河猴的研究中,我们描述了一种焦虑气质内表型,它与过度焦虑和恐惧相关反应以及右侧额叶脑区电活动增加有关。为了研究杏仁核在介导这种内表型和其他恐惧反应中的作用,我们用选择性保留纤维的鹅膏蕈氨酸损毁杏仁核来制备猴子模型。双侧杏仁核损毁超过95%的猴子中,非条件性特质样焦虑 - 恐惧反应保持完好。此外,损毁并未影响脑电图额叶不对称性。然而,双侧杏仁核损毁超过70%的猴子,对诸如接触蛇和陌生的威胁性同种动物所引发的急性非条件性恐惧反应减弱。这些发现表明,灵长类动物的杏仁核参与介导一些急性非条件性恐惧反应,但对杏仁核是焦虑气质的行为和生理特征的关键结构这一观点提出了挑战。