Causal role of delta-beta coupling for goal-directed behavior in anhedonia

δ-β耦合对快感缺失中目标导向行为的因果作用

基本信息

  • 批准号:
    10371650
  • 负责人:
  • 金额:
    $ 9.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-13 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

PROPOSAL SUMMARY/ABSTRACT Anhedonia – the inability to seek-out and experience pleasure – is a common symptom in depression that predicts treatment resistance and is sometimes exacerbated by first-line antidepressants. Anhedonia falls within the “Positive Valence System” of the Research Domain Criteria framework that comprises two primary components: “liking” and “wanting.” The “liking,” or consummatory, component reflects the evaluation of rewards reliant on the medial prefrontal cortex and ventral striatum. The “wanting,” or anticipatory, component modulates the degree to which effort is expended in goal-directed behavior reliant on the lateral prefrontal cortex and dorsal striatum. Previous research found decreased neural activity in both of these neural circuits in depressed patients with anhedonia but has not causally investigated the role of these neural circuits, or their temporal dynamics, in different components of reward-based decision-making. The preliminary data found decreased goal-directed behavior in depressed patients with anhedonia and reduced cross-frequency coupling between the phase of delta oscillations (2-4 Hz) in lateral prefrontal cortex and task-modulated beta oscillations (15-30 Hz) (delta-beta coupling). The objective of this research plan is to dissect the causal role of frontal-striatal circuity in different components of reward-based decision-making and their impairment in anhedonia. The central hypothesis is that anhedonia arises from decreased goal-directed behavior and disruption of delta-beta coupling in lateral prefrontal cortex and dorsal striatum. The rationale is that spatially and temporally-targeted non-invasive brain stimulation during performance of a reward-based decision-making task will provide causal evidence for which network dynamics are impaired in anhedonia. Accordingly, the three specific aims are (1) Causally dissociate the neural circuits that implement goal-directed behavior and reward-evaluation in decision-making, (2) Increase goal- directed behavior in depressed patients with anhedonia using network-targeted non-invasive brain stimulation, and (3) Investigate target engagement of delta-beta coupling in a potential treatment paradigm with network- targeted stimulation in a randomized clinical trial for depressed patients with symptoms of anhedonia. This proposal is significant because it will causally evaluate mechanistic models of the networks and cognitive processes that are disrupted in anhedonia. The work is innovative because it uses concurrent neurophysiology and neurostimulation, integrates high-resolution spatial and temporal investigation tools, and utilizes individualized stimulation parameters such as subcortical-targeting with functional-connectivity and task-specific frequency targeting. The positive impact of this proposal is a refined definition of anhedonia based in biological mechanism that may have transdiagnostic relevance for other psychiatric illnesses such as schizophrenia and substance use disorder. The implication of this proposal is that the knowledge gained can be directly used for the development of novel interventions using precision medicine.
提案摘要/摘要 快感缺失--无法寻找和体验快乐--是抑郁症的一种常见症状, 预示着治疗抵抗,有时会因一线抗抑郁药而加剧。快感缺失福尔斯属于 研究领域标准框架的"正价系统",包括两个主要的 组成部分:“喜欢”和“想要”。“喜欢”或完善性成分反映了对奖励的评价 依赖于内侧前额叶皮层和腹侧纹状体"想要"或预期成分调节 努力在多大程度上是花费在目标导向的行为依赖于外侧前额叶皮层和背侧 纹状体先前的研究发现,抑郁症患者的这两种神经回路的神经活动都有所减少 但没有因果关系研究这些神经回路的作用,或他们的时间动态, 基于奖励的决策的不同组成部分。初步数据发现, 行为在抑郁症患者的快感缺乏和减少交叉频率之间的耦合相位 δ振荡(2 - 4 Hz)在外侧前额叶皮层和任务调制的β振荡(15 - 30 Hz)(δ-β 耦合)。本研究计划的目的是剖析额-纹状体环路在不同脑区中的因果作用。 奖励为基础的决策及其在快感缺失的损害的组成部分。核心假设是, 快感缺乏是由于目标导向行为的减少和外侧前额叶的δ-β耦合的破坏引起的。 皮质和背侧纹状体。基本原理是,空间和时间靶向的非侵入性脑刺激 在基于奖励的决策任务的执行过程中,将提供因果关系的证据, 动力学在快感缺乏中受损。因此,这三个具体目标是:(1)因果地分离神经元, 在决策中实现目标导向行为和奖励评估的电路,(2)增加目标- 使用网络靶向非侵入性脑刺激治疗快感缺失的抑郁症患者的定向行为, 和(3)研究在具有网络的潜在治疗范例中δ-β偶联的靶点接合, 在一项随机临床试验中,对有快感缺乏症状的抑郁症患者进行靶向刺激。这 该提案是重要的,因为它将因果评估网络和认知的机制模型 在快感缺乏症中被破坏的过程。这项工作是创新的,因为它使用并发神经生理学 和神经刺激,集成了高分辨率的空间和时间调查工具,并利用 个性化的刺激参数,例如具有功能连接性和任务特异性的皮质下靶向 频率瞄准这一建议的积极影响是一个基于生物学的快感缺乏的精确定义。 可能对其他精神疾病(如精神分裂症)具有转诊断相关性的机制, 物质使用障碍这一建议的含义是,所获得的知识可以直接用于 使用精准医疗开发新的干预措施。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Justin M Riddle其他文献

Justin M Riddle的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Justin M Riddle', 18)}}的其他基金

Causal role of delta-beta coupling for goal-directed behavior in anhedonia
δ-β耦合对快感缺失中目标导向行为的因果作用
  • 批准号:
    10917463
  • 财政年份:
    2021
  • 资助金额:
    $ 9.17万
  • 项目类别:
Causal role of delta-beta coupling for goal-directed behavior in anhedonia
δ-β耦合对快感缺失中目标导向行为的因果作用
  • 批准号:
    10488259
  • 财政年份:
    2021
  • 资助金额:
    $ 9.17万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了