Intracranial Neurophysiological Signatures of Fear and Anxiety in Humans

项目总结/摘要 对啮齿动物的研究积累的证据表明，对威胁性刺激的情绪反应依赖于 包括内侧前额叶皮质在内的焦虑处理网络内的神经生理学变化 （mPFC）、基底外侧杏仁核（BLA）和腹侧海马（vHPC）[1]。由于啮齿类动物研究经常使用 实验室动物模型（类似于健康人类）目前还不清楚这些发现是否会转化为人类 mPFC-BLA-vHPC网络，特别是在具有各种焦虑水平的个体中，例如创伤后应激 广泛性焦虑症（GAD）或创伤后应激障碍（PTSD）。拟议的项目将实施一项前所未有的 颅内脑电图（iEEG）记录和颅内电刺激（iES）平台， mPFC-BLA-vHPC振荡活动在实验室和自然恐惧为基础的任务，使用沉浸式虚拟 虚拟现实（VR）技术和可穿戴生物传感器，能够记录生理（眨眼、心率 变异性[HRV]、皮肤电导反应[SCR]和瞳孔大小）。通过跨学科合作 加州大学洛杉矶分校和退伍军人管理局大洛杉矶医疗保健系统（VAGLAHS）之间， 拟议项目将访问80名植入mPFC、BLA和/或vHPC深度的癫痫受试者 不同程度的焦虑相关处理失调的电极。由于我们的研究涉及基本的 关于mPFC-BLA-vHPC振荡在人类恐惧和焦虑中的作用的问题，结果将弥合 研究结果跨越物种，并为帮助未来的焦虑症患者奠定科学基础。 紊乱

Project Summary/Abstract Accumulating evidence from studies in rodents suggests that emotional reactions to threatening stimuli rely on neurophysiological changes within an anxiety-processing network that includes the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC) [1]. Since rodent studies often use laboratory animal models (similar to healthy humans) it is unclear whether findings will translate to the human mPFC-BLA-vHPC network especially in individuals with various levels of anxiety such as post-traumatic stress disorder (PTSD) or generalized anxiety disorder (GAD). The proposed project will implement a first-of-its-kind platform for intracranial electroencephalographic (iEEG) recording and intracranial electrical stimulation (iES) of mPFC-BLA-vHPC oscillatory activity during laboratory and naturalistic fear-based tasks using immersive virtual reality (VR) technology and wearable biometric sensors capable of recording physiology (eye-blinks, heart rate variability [HRV], skin conductance response [SCR], and pupil size). Through an interdisciplinary collaboration between UCLA and the Veteran’s Administration Greater Los Angeles Healthcare System (VAGLAHS) the proposed project will have access to 80 epilepsy participants implanted with mPFC, BLA, and/or vHPC depth electrodes with varying levels of dysregulatory anxiety-related processing. Since our studies address basic questions about the role of mPFC-BLA-vHPC oscillations in human fear and anxiety, the results will bridge findings across species and lay the scientific foundation for helping future patients with debilitating anxiety disorders.