Using novel virtual reality tasks to identify neural mechanisms of discrimination learning in PTSD

创伤后应激障碍(PTSD)是一种非常普遍的、使人衰弱的疾病。尽管 关于创伤后应激障碍的病理生理学特征，目前还没有建立生物标记物来帮助 诊断、治疗进展和治疗反应的预测。新的证据表明 创伤后应激障碍是通过对威胁和奖励中的语境/线索的功能失调的辨别来调节的 加工，涉及海马体、伏隔核、杏仁核和前额叶皮质。 仍然，语境成分，或环境(心理)的心理边界的形成 表示)中描述威胁/安全和奖励/非奖励提示/信号 环境，以及这些过程的神经回路在创伤后应激障碍中仍有待研究 语境处理通常会受到损害。 我开发了两个虚拟现实(VR)任务来检查威胁和奖励歧视，以 使用以下工具评估环境中学习价歧视的潜在机制 位置特定的信息。简而言之，本研究使用的任务包括中性(CS-)和 威胁或奖励(CS+)区域，在单一环境中，参与者必须使用空间 学习区分这两个领域的信息。这项任务旨在揭示大脑 参与学习的地区预测环境奖励的地点。 这项研究计划旨在调查创伤后应激障碍患者之间的脑活动差异。 80例，无创伤后应激障碍的创伤暴露对照组(TE；n=80)，健康对照组(HC；n=80)。 VR范型期间的功能磁共振成像(FMRI)将用于阐明 威胁和奖励学习与辨别加工的神经机制 组。多个级别的评估将包括多模式磁共振成像，以及外围设备 测量唤醒(例如，皮肤电导反应)、眼球跟踪和 学习。 这是澄清威胁和奖励歧视学习过程的第一步 环境，特别是为了阐明神经信号是否特定于价信号或 一般的创伤后应激障碍精神病理学。从长远来看，这项研究将阐明具体的 辨别学习所需的脑区在一个将会进步的环境中的作用 发展对创伤后应激障碍和其他精神病的有效诊断和治疗。

Post-traumatic stress disorder (PTSD) is a highly prevalent and debilitating disorder. Despite efforts to characterize PTSD pathophysiology, no biomarkers have been established to aid in diagnosis, treatment development, and prediction of treatment response. New evidence poses that PTSD is mediated by dysfunctional discrimination of context/cues in both threat and reward processing, involving the hippocampus, nucleus accumbens, amygdala, and prefrontal cortex. Still, the contextual component, or the formation of mental boundaries of the environment (mental representations) that delineate threat/safety and reward/non-reward cues/signals within a single environment, and the neural circuits of these processes are yet to be studied in PTSD where contextual processing is often impaired. I have developed two virtual reality (VR) tasks to examine threat and reward discrimination, to assess the underlying mechanisms of learning valence discrimination within an environment using location-specific information. Briefly, the task used for this study consists of neutral (CS-) and threat or reward (CS+) areas, within a single environment, and participants must use spatial information to learn to discriminate between both areas. The task is designed to reveal brain regions involved in learning locations predictive of environmental reward. This research proposal aims to investigate brain activity differences between patients with PTSD (n=80), trauma-exposed controls without PTSD (TE; n=80), and healthy controls (HC; n=80). Functional magnetic resonance imaging (fMRI) during the VR paradigm will be used to clarify the neural mechanisms underlying threat and reward learning and discrimination processing across groups. Multiple levels of assessment will include multimodal MRI, coupled with peripheral measures of arousal (e.g., Skin Conductance Response), eye-tracking, and subjective ratings of learning. This is a first step to clarify the process of threat and reward discrimination learning within an environment, particularly to elucidate if the neural signatures are specific to valence signaling or to PTSD psychopathology in general. In the long term, this research will shed light on the specific role of brain areas needed for discrimination learning within an environment which will advance the development of effective diagnostics and treatments for PTSD and other psychopathologies.