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

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.