The Neurobiology of Emotional Experience in Patients with Schizophrenia: Using Investigations of Odor Valence Perception to Understand the Emotion Paradox

情感缺陷，如情感平淡和快感缺乏是精神分裂症的核心特征，但患者的自我报告表明，这种情绪反应的外在表达减少往往伴随着内部情绪体验的增加。行为研究表明，这可能是由积极和消极症状选择性地影响情绪刺激的效价谱的不同部分引起的。然而，到目前为止，这些观察结果背后的神经过程知之甚少。最近的工作在健康对照组强调存在多个输入路径的杏仁核。来自这些不同网络的神经输入的组合被认为调节了杏仁核对情绪刺激的反应。拟议的项目将调查这些途径的相对贡献异常杏仁核激活情绪刺激跨效价和唤醒维度的精神分裂症，以及这种相互作用是如何影响疾病的特点。作为第一步，我们建议设计一个气味电池，系统地改变整个情感空间的刺激强度和效价，并仔细验证这种电池在健康对照组。然后，该电池将用于行为评估气味效价感知和疾病特征之间的关系，并使用功能性磁共振成像，表征代表情感价值的神经网络之间的完整和干扰关系。特别是，我们的目标是分离的DLPFC，ACC和OFC的前额叶网络的贡献，据推测subserving负性情绪反应的下调，和奖励网络，包括腹侧纹状体和背侧核。该项目的目的是建立一个基于情绪缺陷的干预的理论基础，基于患者呈现的特定疾病特征。

Emotional deficits such as flat affect and anhedonia are core features of schizophrenia, but self-report from patients suggests that this reduced outward expression of emotional reactivity is paradoxically often accompanied by increased internal emotional experience. Behavioral studies suggest that this may be caused by positive and negative symptoms selectively affecting different parts of the valence spectrum of emotional stimuli. The neural processes underlying these observations are, however, to date poorly understood. Recent work in healthy control subjects emphasizes the existence of multiple input paths to the amygdala. The combination of neural input from these different networks is thought to modulate the amygdala response to emotional stimuli. The proposed project will investigate the relative contribution of these pathways to abnormal amygdala activation to emotional stimuli across valence and arousal dimensions in schizophrenia, and how this interplay is affected by illness characteristics. As a first step, we propose to design an odor battery which systematically varies stimulus intensity and valence across the entire affective space, and carefully validate this battery in healthy control subjects. This battery will then be used to behaviorally assess relationships between odor valence perception and illness characteristics and, using functional magnetic resonance imaging, characterize intact and disturbed relationships among the neural networks representing emotional value. In particular, the goal is to dissociate the contribution of a prefrontal network of DLPFC, ACC and OFC, supposedly subserving downregulation of a negative emotional response, and the reward network, including ventral striatum and nucleus accumbens. The aim of the project is to build a theoretical foundation for symptom-based intervention for emotional deficits, based on specific illness characteristics that a patient presents with.