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

• 批准号: 10367990
• 负责人: Wilder T Doucette
• 金额: $ 17.3万
• 依托单位: DARTMOUTH-HITCHCOCK CLINIC
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10367990
• 关键词: Address; Appetitive Behavior; Area; Attention deficit hyperactivity disorder; Behavior; Behavioral; Bilateral; Binge Eating; Brain; Brain region; Clinical; Complement; Computing Methodologies; Corpus striatum structure; Costs and Benefits; Dangerousness; Data; Decision Making; Deep Brain Stimulation; Development; Diagnostic; Disease model; Drug usage; Eating; Electrophysiology (science); Ensure; Frequencies; Gambling; Goals; Human; Impulsivity; Individual; Intervention; Life Cycle Stages; Link; Logic; Measures; Medial; Mental disorders; Mentors; Mentorship; Nucleus Accumbens; Pathologic; Patients; Pattern; Performance; Persons; Phase; Physicians; Population; Prefrontal Cortex; Protocols documentation; Psychiatry; Quality of life; Research; Rodent; Rodent Model; Scientist; Substance Use Disorder; Suicide; System; Task Performances; Therapeutic; Time; Training; Transcranial magnetic stimulation; Variant; Violence; Work; base; clinical care; computerized tools; discounting; experience; high dimensionality; improved; indexing; individual variation; knowledge base; neuropsychiatry; pre-clinical; pre-clinical research; preclinical study; programs; prospective; psychologic; relapse risk; relating to nervous system; sex; substance use; targeted treatment; trait; translational research program

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).

抽象的 在许多精神疾病（例如多动症、躁郁症、饮食失调症）中都观察到冲动和冒险的决策 选择冲动（CI）的潜在心理结构的变化。 和风险选择（RC），可以使用特定任务在临床前和临床人群中进行评估 - CI 的延迟贴现任务和 RC 的风险决策任务 在患者中，CI 和 RC 任务。 与冲动和冒险决策相关的绩效，前瞻性地与有问题的问题相关 行为——赌博、暴饮暴食、药物滥用、暴力和自杀——并且还预测对这些行为的无反应 因此，可以使决策正常化的治疗，反映在 CI 或复发风险的改善上。 RC 任务表现可能对一系列神经精神疾病产生有意义的临床影响。 先前的研究已将 CI 和 RC 任务表现（啮齿动物和人类）与特定的 皮质纹状体活动模式，但很少有批准的神经精神疾病治疗方法 开发的目的是针对和治疗性操纵这些系统级神经活动 因此，该提案将：（1）确定与 CI 和 RC 相关的皮质纹状体活动模式。 任务表现；（2）确定如何针对不同的皮质纹状体区域进行深部脑刺激 (DBS) 改变皮质纹状体活动；(3) 使用 DBS 调节活动模式并将其与 CI 相关联 该提案将确定神经系统级别的治疗目标。 帮助开发基于回路的干预措施（例如 DBS 和经颅磁刺激 - TMS） 一系列精神疾病的适应不良决策。 我在该提案中的主要目标是建立一个独立的研究计划来解决 以下问题：与心理领域相关的神经系统级活动模式是什么 疾病？；以及如何利用神经系统层面对跨诊断领域的理解 使基于循环的干预措施能够发挥其治疗潜力？ 从紊乱食欲行为模型到常见功能域的临床研究 许多精神疾病的病理学将增强我的研究的转化相关性 为了实现这一转变并处于计算精神病学的最前沿，我必须获得额外的知识。 用于高维分析的高级行为协议和尖端计算工具的培训 K08 中概述的训练补充了我现有的知识库（电生理学和 基于电路的干预措施）并与拟议的具体目标很好地结合起来，以提供获得收益的背景 通过课程作业和一对一指导（内部和外部）在这些关键培训领域积累经验 外部的）。

项目成果

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。

• 发表时间: 2019
• 影响因子: 4.3
• 作者: Dwiel, Lucas L;Khokhar, Jibran Y;Connerney, Michael A;Green, Alan I;Doucette, Wilder T
• 通讯作者: Doucette, Wilder T

A Simple, Lightweight, and Low-Cost Customizable Multielectrode Array for Local Field Potential Recordings.

用于局部场电位记录的简单、轻量级且低成本的可定制多电极阵列。

• 发表时间: 2023-08
• 影响因子: 3.4
• 作者: Quansah Amissah, Richard;Albeely, Abdalla M;Bragg, Elise M;Perreault, Melissa L;Doucette, Wilder T;Khokhar, Jibran Y
• 通讯作者: Khokhar, Jibran Y