The Neural Basis of the Positivity Offset as a Mechanism of Avolition in Schizophrenia

项目总结 孤独感(例如，减少动机和对目标导向行为的投入)是一种核心的负面症状， 这是预测精神分裂症患者功能障碍的最有力指标之一。当前的心理社会和 药物干预在治疗心绞痛方面效果不佳，这主要是由于人们对其了解有限。 潜在的机制。涉及皮质-纹状体功能障碍的领先概念框架 奖励过程中的异常提高了该领域对病因的理解 然而，这项工作尚未导致治疗方面的重大突破。这些 模型假设精神分裂症患者的享乐反应是完整的，我们实验室最近提出的这一理论可能是 还为时过早。在卡奇奥波的评估空间模型的启发下，运用情感科学的方法 情绪体验，我们最近证明了情绪体验中的异常确实有助于 精神分裂症患者的精神分裂，表现为积极程度的降低。正性偏移量是自适应 一种功能，其特点是在低水平的唤醒时，积极情绪比消极情绪更平衡 促进有动机的行为。我们实验室的初步数据表明，正性偏移在 精神分裂症与临床评定的阴性症状有关，这表明它可能提供了一种新的 对偷盗行为的解释。在目前的研究中，我们的目标是通过以下方式扩展这些发现：1)识别 作为正性偏移量基础的电路，2)确定正性偏移量是否也在实数中减小。 精神分裂症的世界，以及3)确定积极程度的减少是否抵消了相关的神经 过程预示着日常生活中的消亡。具体地说，我们将使用fMRI来测量 情绪体验任务，以验证内侧前额叶皮质激活减少的假设， 伏隔核和尾状核与精神分裂症患者的正性抵消减少有关。 此外，我们将研究这些区域的激活是否预示着正性偏移量的减少和 在现实世界中，这将通过主动和被动的数字表型来测量。这种方法 解决了对情感和神经机制的理解上的差距 对日常运作的影响。这些发现有可能为个人化的治疗方法提供参考 通过识别可作为治疗靶点的特定神经回路和情感过程进行治疗 药理学和心理社会干预。此外，很少有临床研究人员接受过采用 研究阴性症状的跨学科、多模式方法。拟议的研究和培训计划 旨在满足这一领域的迫切需求，为申请者提供尖端技能 神经成像和数字表型方法，以检验关于AVOLATION起源的假说。

PROJECT SUMMARY Avolition (e.g., reduced motivation and engagement in goal-directed behavior) is a core negative symptom and one of the strongest predictors of functional disability in schizophrenia. Current psychosocial and pharmacological interventions are ineffective at treating avolition, largely due to limited understanding of its underlying mechanisms. Leading conceptual frameworks implicating dysfunctional cortico-striatal interactions and abnormalities in reward processing have improved the field's understanding of the etiological underpinnings of avolition; however, this work has not yet led to significant breakthroughs in treatment. These models assume that the hedonic response is intact in schizophrenia, a theory our lab recently proposed may be premature. By applying an affective science approach informed by Cacioppo's Evaluative Space Model of Emotional Experience, we recently demonstrated that abnormalities in emotional experience do contribute to avolition in schizophrenia, in the form of a reduction in the positivity offset. The positivity offset is an adaptive function characterized by a greater balance of positive than negative emotion at low levels of arousal, which promotes motivated behaviors. Preliminary data from our lab indicates that the positivity offset is reduced in schizophrenia and is associated with clinically rated negative symptoms, suggesting it may offer a novel explanation for avolition. In the current study, we aim to expand these findings by: 1) identifying the neural circuits underlying the positivity offset, 2) determining whether the positivity offset is also reduced in the real- world in schizophrenia, and 3) determining whether reductions in the positivity offset and associated neural processes predict avolition in everyday life. Specifically, we will use fMRI to measure neural activity during an emotional experience task to test the hypothesis that reduced activation of the medial prefrontal cortex, nucleus accumbens, and caudate nucleus is associated with reductions in the positivity offset in schizophrenia. Additionally, we will examine whether activation in these regions predicts positivity offset reduction and avolition in the real-world, which will be measured via active and passive digital phenotyping. This approach addresses the gap in understanding of the affective and neural mechanisms underlying avolition and their impact on daily functioning. Findings have potential to inform personalized medicine approaches to treating avolition by identifying specific neural circuits and affective processes that can serve as treatment targets for pharmacological and psychosocial interventions. Further, few clinical investigators are trained to adopt a transdisciplinary, multimodal approach to study negative symptoms. The proposed research and training plans are designed to meet this urgent need in the field, providing the applicant with skills in cutting-edge neuroimaging and digital phenotyping methods to test hypotheses about the origins of avolition.