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).

摘要 在许多精神疾病中观察到冲动和冒险的决策（例如，多动症躁郁症进食 物质使用障碍）。选择冲动（CI）的潜在心理结构的变化 和风险选择（RC），可以在临床前和临床人群中使用特定的任务进行评估- 延迟折扣任务CI和风险决策任务RC。在患者中，CI和RC任务 与冲动和风险决策相关的绩效，与有问题的 行为-赌博，暴饮暴食，物质使用，暴力和自杀-也预测不响应 治疗和复发的风险。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，可能在一系列神经精神疾病中具有有意义的临床影响。 先前的研究将CI和RC任务表现（啮齿动物和人类）与特定的 皮质-纹状体活动的模式，但很少有批准的神经精神疾病的治疗方法， 开发的目的是针对和治疗操纵这些系统级神经活动 模式.因此，本研究将：（1）确定与CI和RC相关的皮质-纹状体活动模式 任务表现;（2）确定如何用深部脑刺激靶向不同的皮质-纹状体区域 (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 和RC任务性能变化。该提案将确定神经系统水平的治疗目标， 有助于开发基于电路的干预（例如，DBS和经颅磁刺激（TMS） 在一系列精神疾病中的适应不良决策。 我的主要目标是建立一个独立的研究计划， 以下问题：与心理领域相关的神经系统水平的活动模式是什么？ 生病了？以及如何利用神经系统层面对跨诊断域的理解， 使基于回路的干预能够发挥其治疗潜力？我相信把我的前- 临床研究从紊乱的食欲行为模型到共同的功能领域， 在许多精神疾病的病理将提高我的研究翻译相关性 程序.为了实现这一转变，并站在计算精神病学的最前沿，我必须获得额外的知识。 培训先进的行为协议和尖端的计算工具，用于分析高维 神经数据本K 08中概述的培训补充了我现有的知识基础（电生理学和 基于回路的干预措施），并与拟议的具体目标保持一致，以提供获得 通过课程工作和一对一指导（内部和外部）， 外部）。

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。

• DOI: 10.1371/journal.pcbi.1006838
• 发表时间: 2019
• 期刊: PLoS computational biology
• 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: ENEURO
• 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.