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

情感缺陷，如扁平情感和快感缺乏症是精神分裂症的核心特征，但患者的自我报告表明，这种情绪反应的外部表达减少往往伴随着内在情绪体验的增加，这是自相矛盾的。行为研究表明，这可能是由于阳性和阴性症状选择性地影响情绪刺激效价谱的不同部分造成的。然而，迄今为止，人们对这些观察结果背后的神经过程知之甚少。最近对健康对照受试者的研究强调了通往杏仁核的多种输入路径的存在。来自这些不同网络的神经输入的组合被认为可以调节杏仁核对情绪刺激的反应。该项目将研究这些途径在精神分裂症患者的效价和觉醒维度上对杏仁核异常激活的相对贡献，以及这种相互作用如何受到疾病特征的影响。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，并在健康对照对象中仔细验证该电池。然后，该电池将用于行为评估气味价感知与疾病特征之间的关系，并使用功能磁共振成像来表征代表情感价值的神经网络之间完整和受干扰的关系。具体来说，目标是分离由DLPFC、ACC和OFC组成的前额叶网络的作用，该网络被认为有助于消极情绪反应的下调，以及包括腹侧纹状体和伏隔核在内的奖励网络。该项目的目的是根据患者所表现出的特定疾病特征，为基于症状的情绪缺陷干预建立理论基础。

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.