Neural Circuitry of Threat Perception: Implications for Anxiety and Paranoia

 描述（由申请人提供）：焦虑和偏执可能导致对生活质量的重大和削弱性影响。焦虑和偏执都被认为与威胁检测系统的异常有关，该系统包括杏仁核等边缘系统结构以及与新皮层区域的相互作用。该提案旨在通过在成人大脑内的相关结构中进行生理记录来直接检查威胁检测神经回路的时空动态。我们将记录植入电极的癫痫患者的侵入性神经生理数据，同时他们执行旨在区分威胁信号的认知任务。凭借高时空分辨率，广泛和动态的记录，我们将能够调查以下基本问题：1）威胁刺激（单词和视听输入）是否比非威胁刺激更大程度地参与杏仁核和相关的内侧颞叶结构？2)在偏执和焦虑水平升高的受试者中，边缘系统对非威胁性刺激的参与程度是否更高？3)在威胁刺激的加工过程中，新皮层（包括语言和视觉皮层）与内侧颞叶结构之间的相互作用是否增强？(4)威胁检测是否对特定的输入方式（如语义或视听访问）保持不变？为了解决这些问题，我们组建了一个具有神经病学和精神病学（Weisholtz博士，Silbersweig博士，Butler博士），癫痫（Weisholtz博士，Dworetzky博士，Madsen博士）以及系统和计算神经科学（Kreiman博士）专业知识的团队。我们将通过检查大脑感兴趣区域的局部诱发电位和诱发高频活动以及对比威胁和中性刺激之间的反应来解决这些问题。区域间的相互作用将通过计算区域间振荡锁相和相关伽马功率的程度来探讨。我们将使用偏执狂评定量表和状态-特质焦虑量表评估偏执狂和焦虑的程度。这些研究工作将有助于更好地了解负责焦虑和偏执狂的内部回路，并最终开发预测工具和靶向治疗。

 DESCRIPTION (provided by applicant): Anxiety and paranoia can lead to a significant and debilitating impact on quality of life. Both anxiety and paranoia are believed to involve abnormalities of a threat detection system that includes limbic structures such as the amygdala and interactions with neocortical areas. This proposal aims to directly examine the spatiotemporal dynamics underlying the threat detection neural circuit by performing physiological recordings in the relevant structures within the adult human brain. We will record invasive neurophysiological data in epilepsy patients implanted with electrodes for clinical reasons while they perform cognitive tasks aimed to discriminate threat signals. By virtue of the high spatiotemporal resolution, extensive and dynamic recordings, we will be able to investigate the following fundamental questions: 1) Do threat stimuli (words and audiovisual inputs) engage the amygdala and related medial temporal structures to a greater degree than non-threatening stimuli? 2) Is there a greater degree of limbic engagement to non-threatening stimuli in subjects with elevated levels of paranoia and anxiety? 3) Is the interaction between neocortical areas (including language and visual cortex) and medial temporal structures enhanced during the processing of threat stimuli? (4) Is threat detection invariant to the specific input modalities suh as semantic or audiovisual access? To address these questions, we have assembled a team with expertise in Neurology and Psychiatry (Dr. Weisholtz, Dr. Silbersweig, Dr. Butler), epilepsy (Dr. Weisholtz, Dr. Dworetzky, Dr. Madsen) and systems and computational neuroscience (Dr. Kreiman). We will address these questions by examining localized evoked potentials and induced high- frequency activity in the brain regions of interest and by contrasting the response between threat and neutral stimuli. Interactions between regions will be explored by calculating the degree of inter-regional oscillatory phase locking and correlated gamma power. We will assess the degree of paranoia and anxiety using the Paranoia Rating Scale and the State-Trait Anxiety Inventory.These research efforts will contribute to a better understanding of the inner circuits responsible for anxiety and paranoia, and ultimately to the development of predictive tools and targeted therapies.