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

积极性抵消作为精神分裂症意志机制的神经基础

• 批准号: 10314527
• 负责人: Lisa Ann Bartolomeo
• 金额: $ 4.01万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314527
• 关键词: Adaptive Behaviors; Address; Adopted; Affective; Arousal; Behavior; Behavioral; Bilateral; Cellular Phone; Clinical; Clinical Investigator; Corpus striatum structure; Data; Decision Making; Diagnostic; Ecological momentary assessment; Emotional; Emotions; Equilibrium; Etiology; Exhibits; Exploratory Behavior; Functional Magnetic Resonance Imaging; Goals; Image; Impairment; Intervention; Laboratories; Lead; Learning; Libraries; Life; Measures; Medial; Medical; Methods; Modeling; Motivation; Negative Valence; Normalcy; Nucleus Accumbens; Outpatients; Participant; Patient Self-Report; Patients; Pharmacology; Phenotype; Prefrontal Cortex; Process; Psychological reinforcement; Research Training; Rewards; Schizophrenia; Science; Seminal; Series; Space Models; Symptoms; Testing; Theoretical model; Work; affective disturbance; affective neuroscience; base; caudate nucleus; cognitive process; cost; daily functioning; design; digital; emotional experience; fighting; functional disability; hedonic; improved; indexing; interest; investigator training; motivated behavior; multimodality; neural circuit; neuroimaging; neuromechanism; novel; personalized medicine; positive emotional state; premature; psychosocial; relating to nervous system; response; reward processing; sensor; skills; theories

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.

项目概要 意志缺失（例如，动机和对目标导向行为的参与度降低）是一种核心负面症状， 精神分裂症功能障碍的最强预测因素之一。目前的心理社会和 药物干预对于治疗无欲症无效，很大程度上是由于对其的了解有限。 底层机制。涉及功能失调的皮质纹状体相互作用的主要概念框架 奖励处理的异常提高了该领域对病因的理解 意志的基础；然而，这项工作尚未在治疗方面取得重大突破。这些 模型假设精神分裂症的享乐反应是完整的，我们实验室最近提出的理论可能是 为时过早。通过应用由 Cacioppo 的评估空间模型提供的情感科学方法 情绪体验，我们最近证明情绪体验的异常确实会导致 精神分裂症中的意志力下降，表现为积极抵消的减少。正性偏移是自适应的 功能的特点是在低唤醒水平下积极情绪比消极情绪具有更大的平衡，这 促进积极的行为。我们实验室的初步数据表明，积极偏移在 精神分裂症并与临床评定的阴性症状相关，这表明它可能提供一种新的治疗方法 对无欲的解释。在当前的研究中，我们的目标是通过以下方式扩展这些发现：1）识别神经元 正性偏移背后的电路，2）确定正性偏移是否也在实际中减少 精神分裂症的世界，以及 3) 确定积极性的减少是否会抵消和相关的神经元 过程预测日常生活中的意愿。具体来说，我们将使用功能磁共振成像来测量神经活动 情绪体验任务来测试内侧前额叶皮层激活减少的假设， 伏隔核和尾状核与精神分裂症阳性偏移的减少有关。 此外，我们将检查这些区域的激活是否可以预测积极性偏移的减少以及 现实世界中的意志，将通过主动和被动数字表型来测量。这种做法 解决了对无欲及其背后的情感和神经机制的理解上的差距 对日常功能的影响。研究结果有可能为个性化医学治疗方法提供信息 通过识别特定的神经回路和情感过程来作为治疗目标 药物和心理社会干预。此外，很少有临床研究人员接受过采用 跨学科、多模式的方法来研究阴性症状。拟议的研究和培训计划 旨在满足该领域的这一迫切需求，为申请人提供尖端技能 神经影像和数字表型分析方法来检验有关意志起源的假设。