Neural mechanisms of affective processing in prefrontal-limbic circuits

前额叶边缘环路情感处理的神经机制

• 批准号: 10016795
• 负责人: Peter Rudebeck
• 金额: $ 57.71万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-11 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10016795
• 关键词: Acute; Affect; Affective; Amygdaloid structure; Anhedonia; Anterior; Anxiety Disorders; Area; Behavior; Behavioral; Brain; Chronic; Code; Corpus striatum structure; Data; Decision Making; Deep Brain Stimulation; Diffusion; Disease; Electric Stimulation; Event; Failure; Fiber; Foundations; Frequencies; Functional disorder; Goals; Human; Image; Individual; Intervention; Knowledge; Lesion; Light; Limbic System; Magnetic Resonance Imaging; Major Depressive Disorder; Mental Depression; Methods; Monkeys; Mood Disorders; Neurons; Neurosciences; Operant Conditioning; Pathway interactions; Patients; Pattern; Physiological; Prefrontal Cortex; Primates; Process; Randomized Clinical Trials; Research; Rewards; Role; Schizophrenia; Signal Transduction; Site; Specificity; Structure; Testing; Ventral Striatum; Work; base; behavior influence; behavioral response; cingulate cortex; expectation; experience; image guided; imaging modality; imaging study; innovation; mood symptom; neural circuit; neural patterning; neuromechanism; novel; pleasure; relating to nervous system; response; reward expectancy; reward processing; theories; white matter

Project summary Anhedonia is a defining symptom of mood disorders and anxiety disorders and is characterized by a loss of positive affect from rewarding experiences. Current theories of anhedonia emphasize that it consists of two distinct components: one is related to the expectation of reward, the other to the pleasure from receiving rewards. Understanding how the brain processes expected and received rewards at the level of single neurons is therefore a key challenge for basic neuroscience. Imaging studies indicate that one part of the prefrontal cortex, the subcallosal anterior cingulate cortex (ACC) is active when rewards are expected and is altered in individuals with anhedonia. Corroborating this finding, data from studies of monkeys with lesions of the subcallosal ACC indicate that this area is important for behavior related to the expectation, but not the receipt of rewards. However, no approach to date has been able to provide a circuit-level understanding of how the subcallosal ACC influences reward expectation. This level of understanding is important as deep brain stimulation of subcallosal ACC and nearby white matter pathways alleviates anhedonia in some patients. This intervention is hypothesized to work by altering functional interaction between subcallosal ACC and either amygdala or ventral striatum. Which pathway is more important for controlling behavior related to reward expectation or the requisite activity patterns is unknown. Our goal here is to determine the neural mechanisms engaged in the subcallosal ACC-amygdala-VS circuit when rewards are expected and then received. We hypothesize that the role of the subcallosal ACC is to modulate reward encoding within ventral striatum and amygdala during reward expectation, but not receipt. To test our hypothesis we will use an innovative combination of single-neuron recordings, field potential recordings, electrical stimulation, diffusion imaging methods, and chemogenetics analyzing the timing of reward-related neural responses and LFP coherence among the three sites under normal physiological conditions, when neurons in subcallosal ACC are chronically activated using chemogenetic methods, and when acute electrical stimulation is applied both under normal conditions and when the area is chronically activated. Completing these aims will fundamentally advance our understanding of the neural circuits and activity patterns that control reward-related behavioral and neural activity in primates as well as providing a circuit level understanding of how subcallosal ACC influences expected reward processing. This level of understanding has the potential to inform and help refine pathway- specific interventions for all disorders characterized by a loss pleasure from reward, such as depression as well as schizophrenia.

项目摘要 Anhedonia是情绪障碍和焦虑症的定义症状，其特征是失去 奖励经验的积极影响。当前的Anhedonia理论强调，它由两个 不同的组成部分：一个与奖励的期望有关，另一个与接受的乐趣有关 奖励。了解大脑如何在单个神经元的水平上进行预期并获得奖励 因此，是基本神经科学的关键挑战。成像研究表明前额叶的一部分 皮层，前扣带回皮层（ACC）是有效的，当期望奖励并改变 患有Anhedonia的人。证实了这一发现，来自猴子研究的数据 亚callosal ACC表明该区域对于与期望相关的行为很重要，但没有收据 奖励。但是，迄今为止尚无方法能够提供对电路级的了解 亚易体育ACC影响奖励期望。这种理解水平很重要 在某些患者中，刺激亚易毛ACC和附近的白质途径可减轻抗抗酸。这 假设干预可以通过改变亚易毛ACC和任何一个之间的功能相互作用来工作 杏仁核或腹纹状体。哪种途径对于控制与奖励有关的行为更为重要 期望或必要的活动模式未知。我们的目标是确定神经机制 预计然后获得奖励时，参与了亚果callosal Acc-amygdala-VS电路。我们 假设亚易毛ACC的作用是调节腹侧纹状体内编码的奖励，并且 在奖励期望期间，杏仁核，但没有收据。为了检验我们的假设，我们将使用创新 单神经元记录，现场潜在记录，电刺激，扩散成像的组合 方法和化学遗传学分析了与奖励相关的神经反应和LFP相干性的时间 在正常生理条件下的三个部位中，当supcallosal ACC中的神经元长期存在时 使用化学发生方法激活，并在正常下施用急性电刺激 条件以及该区域长期激活时。完成这些目标将从根本上促进我们的 了解控制与奖励相关行为和神经的神经回路和活动模式 灵长类动物的活动，并提供对亚易毛ACC如何影响的电路级别的理解 预期的奖励处理。这种理解水平有可能告知和帮助完善途径 - 对所有疾病的具体干预措施，这些疾病的特征是奖励的损失愉悦感，例如抑郁症 以及精神分裂症。