Computationally guided modulation of cortical-striatal activity: Toward brain stimulation-based treatments for impulsive and risky decision making

计算引导的皮质纹状体活动调节:针对冲动和冒险决策的基于大脑刺激的治疗

基本信息

  • 批准号:
    10367990
  • 负责人:
  • 金额:
    $ 17.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-03-01 至 2024-02-29
  • 项目状态:
    已结题

项目摘要

ABSTRACT Impulsive and risky decision-making are observed in many psychiatric disorders (e.g., ADHD, bipolar, eating and substance use disorders). Variation in the underlying psychological constructs of choice impulsivity (CI) and risky choice (RC), can be evaluated in both pre-clinical and clinical populations using specific tasks—the delay discounting task for CI and the risky decision-making task for RC. In patients, CI and RC task performance associated with impulsive and risky decision-making, relates prospectively to problematic behaviors—gambling, binge eating, substance use, violence and suicide—and also predicts non-response to treatment and risk of relapse. Thus, treatments that can normalize decision-making, reflected in improved CI or RC task performance, could have a meaningful clinical impact across an array of neuropsychiatric conditions. Previous studies have correlated CI and RC task performance (in both rodents and humans) with specific patterns of cortical-striatal activity, but few approved treatments for neuropsychiatric illness have been developed for the purpose of targeting and therapeutically manipulating these systems-level neural activity patterns. Therefore, this proposal will: (1) identify patterns of cortical-striatal activity correlated with CI and RC task performance; (2) determine how targeting diverse cortical-striatal regions with deep brain stimulation (DBS) alters cortical-striatal activity; and (3) use DBS to modulate activity patterns and correlate these with CI and RC task performance changes. This proposal will identify neural systems-level treatment targets that will aid in the development of circuit-based interventions (e.g., DBS and transcranial magnetic stimulation-TMS) for maladaptive decision-making across an array of psychiatric conditions. My primary goal under this proposal is to establish an independent research program that will address the following questions: What are the neural systems-level activity patterns that are relevant to domains of mental illness?; and How can a neural systems-level understanding of trans-diagnostic domains be leveraged to enable circuit-based interventions to reach their therapeutic potential? I believe that transitioning my pre- clinical research from models of disordered appetitive behavior to common domains of function that are pathologic across many psychiatric conditions will enhance the translational relevance of my research program. To make this transition and be at the forefront of computational psychiatry, I must acquire additional training in advanced behavioral protocols and cutting-edge computational tools for analysis of high dimensional neural data. The training outlined in this K08 complements my existing knowledge base (electrophysiology and circuit-based interventions) and aligns well with the proposed Specific Aims to provide a context to gain experience in these key areas of training through course work and one-on-one mentorship (both internal and external).
摘要 冲动和危险的决策在许多精神障碍(如多动症、躁郁症、进食)中被观察到 和物质使用障碍)。选择冲动(CI)潜在心理结构的变异 和风险选择(RC),可以使用特定的任务在临床前和临床人群中进行评估 CI延迟折扣任务和RC风险决策任务。在患者中,CI和RC任务 与冲动和冒险的决策有关的表现,可能与有问题的有关 行为--赌博、暴饮暴食、吸毒、暴力和自杀--也预示着对 治疗和复发风险。因此,可以使决策正常化的治疗,反映在改善的CI或 RC任务表现,可能会对一系列神经精神疾病产生有意义的临床影响。 以前的研究已经将CI和RC任务绩效(在啮齿动物和人类中)与特定的 皮质-纹状体活动的模式,但很少有被批准的神经精神疾病的治疗方法 开发的目的是靶向和治疗操作这些系统级别的神经活动 模式。因此,这一建议将:(1)确定与CI和RC相关的皮质-纹状体活动模式 任务绩效;(2)确定如何通过脑深部刺激来定位不同的皮质-纹状体区域 (3)使用DBS调节活动模式,并将其与CI关联起来 和RC任务绩效的变化。这项提案将确定神经系统级别的治疗目标, 协助开发以电路为基础的干预措施(例如,DBS和经颅磁刺激-TMS) 在一系列精神疾病中做出不适应的决策。 根据这项提议,我的主要目标是建立一个独立的研究计划,以解决 以下问题:与心智领域相关的神经系统水平的活动模式是什么 疾病?;以及如何利用神经系统对跨诊断领域的理解来 使基于电路的干预能够发挥其治疗潜力?我相信把我的预科-- 从食欲障碍模型到常见功能领域的临床研究 许多精神疾病的病理研究将增强我的研究的翻译相关性 程序。为了实现这一转变并走在计算精神病学的前沿,我必须获得额外的 高级行为规程和尖端计算工具的培训,用于高维分析 神经数据。本K08中概述的培训补充了我现有的知识库(电生理学和 以电路为基础的干预措施),并与提议的具体目标很好地保持一致,以提供可获得的背景 通过课程工作和一对一指导(内部和 外部)。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Finding the balance between model complexity and performance: Using ventral striatal oscillations to classify feeding behavior in rats.
寻找模型复杂性和性能之间的平衡:使用腹侧纹状体振荡对大鼠的进食行为进行分类。
  • DOI:
    10.1371/journal.pcbi.1006838
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    4.3
  • 作者:
    Dwiel,LucasL;Khokhar,JibranY;Connerney,MichaelA;Green,AlanI;Doucette,WilderT
  • 通讯作者:
    Doucette,WilderT
A Simple, Lightweight, and Low-Cost Customizable Multielectrode Array for Local Field Potential Recordings.
  • DOI:
    10.1523/eneuro.0212-23.2023
  • 发表时间:
    2023-08
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Amissah, Richard Quansah;Albeely, Abdalla M.;Bragg, Elise M.;Perreault, Melissa L.;Doucette, Wilder T.;Khokhar, Jibran Y.
  • 通讯作者:
    Khokhar, Jibran Y.
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Wilder T Doucette其他文献

Wilder T Doucette的其他文献

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{{ truncateString('Wilder T Doucette', 18)}}的其他基金

Evaluating the potential of neural oscillation biomarkers in a rodent model of intervention outcome variation: Toward personalized mental health care
评估神经振荡生物标志物在干预结果变化的啮齿动物模型中的潜力:走向个性化心理保健
  • 批准号:
    10718156
  • 财政年份:
    2023
  • 资助金额:
    $ 17.3万
  • 项目类别:
NE Modulation of Olfactory Bulb During Learning in Mice
小鼠学习过程中嗅球的 NE 调节
  • 批准号:
    7533459
  • 财政年份:
    2005
  • 资助金额:
    $ 17.3万
  • 项目类别:
NE Modulation of Olfactory Bulb During Learning in Mice
小鼠学习过程中嗅球的 NE 调节
  • 批准号:
    7057157
  • 财政年份:
    2005
  • 资助金额:
    $ 17.3万
  • 项目类别:
NE Modulation of Olfactory Bulb During Learning in Mice
小鼠学习过程中嗅球的 NE 调节
  • 批准号:
    7140732
  • 财政年份:
    2005
  • 资助金额:
    $ 17.3万
  • 项目类别:
NE Modulation of Olfactory Bulb During Learning in Mice
小鼠学习过程中嗅球的 NE 调节
  • 批准号:
    7320264
  • 财政年份:
    2005
  • 资助金额:
    $ 17.3万
  • 项目类别:

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  • 批准号:
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前额皮质中的 Mu-阿片系统:在食欲行为中的作用
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    8145565
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前额皮质中的 Mu-阿片系统:在食欲行为中的作用
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    8008656
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Neural Predictors of Self-Regulation Failure and Success for Appetitive Behavior
食欲行为自我调节失败和成功的神经预测因素
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    2006
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Neural Predictors of Self-Regulation Failure and Success for Appetitive Behavior
食欲行为自我调节失败和成功的神经预测因素
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食欲行为自我调节失败和成功的神经预测因素
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