Arbitration between habitual and goal-directed behavior in obsessive-compulsive disorder: circuit dynamics and effects of noninvasive neurostimulation

强迫症中习惯性行为和目标导向行为之间的仲裁：回路动力学和无创神经刺激的影响

• 批准号: 10012942
• 负责人: Reza Tadayon-Nejad
• 金额: $ 20.28万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-24 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10012942
• 关键词: Address; Adult; Anodes; Arbitration; Area; Behavior; Behavior Control; Behavioral; Biology; Brain; Cathodes; Characteristics; Clinical; Complex; Data; Decision Making; Development; Effectiveness; Environment; Equilibrium; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impairment; Individual; Inferior; Knowledge; Lateral; Left; Link; Mediating; Mental disorders; Mentors; Mentorship; Methodology; Methods; Molecular; Motor; National Institute of Mental Health; Neurosciences; Obsessive compulsive behavior; Obsessive-Compulsive Disorder; Outcome; Participant; Pattern; Performance; Population; Prefrontal Cortex; Records; Research; Research Project Grants; Rewards; Scanning; Scientist; Signal Transduction; Solid; Symptoms; System; Task Performances; Testing; Training; avoidance behavior; base; behavior measurement; behavioral phenotyping; career; career development; clinical phenotype; clinically relevant; cognitive neuroscience; compulsion; effective therapy; neurobehavioral; neuromechanism; novel; patient oriented; putamen; relating to nervous system; skills

Abstract: Dysfunctional decision-making may be a prominent mechanism underlying maladaptive behavior in multiple psychiatric disorders, including obsessive-compulsive disorder (OCD). Debilitating compulsivity and avoidance in OCD are believed to be a direct result of flawed decision-processing. A better understanding of the brain mechanisms of abnormal decision-making in OCD is essential for the development of more effective treatment options. This mentored patient-oriented career development project plans to address this underexplored area. By providing the necessary mentorship and support and building upon the candidate’s solid skillset in basic and clinical neuroscience, the primary goal of this K23 project is to establish the candidate’s career as an independent clinician-scientist with expertise in clinical decision neuroscience. The candidate will benefit from the clinical and academic environments of UCLA and Caltech as well as from a mentorship team with a complementary expertise and exceptional scientific and mentoring records to fill gaps in his knowledge and skills in 3 areas: 1) cognitive neuroscience of decision-making; 2) clinical neuroscience task-based functional magnetic resonance imaging (fMRI) methodology; and 3) noninvasive neurostimulation methodology. Integrated with the above-mentioned training goals, the research project will examine neurobehavioral characteristics of decision-making in OCD. [People utilize two behavioral strategies, goal-directed (GD) and habitual (HB) when engaging in value-based decision-making that involves rewarding or punishing outcomes. Furthermore, an arbitration mechanism has been proposed recently that controls the balance between those two strategies in healthy participants. Arbitration regions (the frontopolar and inferolateral prefrontal cortex (ilPFC)) regulate the goal-directed/habitual decision-making balance by selectively downregulating the activity of the habitual regions (putamen and supplementary motor area). In OCD, an imbalance exists between GD and HB action selection in favor of HB action selection. This project aims to explore the neurobehavioral characteristics of this arbitration mechanism and its relationship with behaviors and clinical phenotypes in OCD by applying cognitive neuroscience, clinical task-based fMRI and transcranial direct current stimulation (tDCS) approaches. Adults with OCD and healthy control participants will perform two tasks while being scanned, and when they receive inhibitory, excitatory, and sham tDCS over the left ilPFC outside of the scanner: I) a decision-making task in which GD and HB strategies compete to control action selection and II) a clinically relevant symptom provocation-avoidance task in which avoidance decisions will be simulated. The project’s research aims are to 1) explore the GD, HB, and arbitration regions’ neural activity and arbitration-habitual circuit connectivity in OCD; 2) examine the association between measures of behavioral performance, arbitration’s neural activity and connectivity, and OCD clinical symptoms; and 3) investigate the behavioral consequences of tDCS over an arbitration region, the left ilPFC, during task performance.]

摘要： 功能失调的决策可能是一个突出的机制，潜在的适应不良的行为，在多个 精神障碍，包括强迫症（OCD）。使人衰弱的强迫性和回避 被认为是错误决策过程的直接结果。更好地了解大脑 强迫症的异常决策机制对于开发更有效的治疗方法至关重要 选项.这一指导性的以病人为导向的职业发展项目计划解决这一探索不足的领域。 通过提供必要的指导和支持，并建立在候选人的基本技能， 和临床神经科学，这个K23项目的主要目标是建立候选人的职业生涯， 独立的临床医生-科学家，具有临床决策神经科学方面的专业知识。候选人将受益于 加州大学洛杉矶分校和加州理工学院的临床和学术环境，以及来自一个导师团队， 互补的专业知识和出色的科学和指导记录，以填补他的知识空白， 3个领域的技能：1）决策的认知神经科学; 2）临床神经科学任务为基础的功能 磁共振成像（fMRI）方法; 3）非侵入性神经刺激方法。 结合上述培训目标，本研究项目将检查神经行为 强迫症的决策特征[人们使用两种行为策略，目标导向（GD）和 当从事涉及奖励或惩罚结果的基于价值观的决策时，会出现习惯性（HB）。 此外，最近还提出了一个仲裁机制，以控制这些因素之间的平衡。 健康参与者的两种策略。仲裁区（额极和下外侧前额叶皮层 （ilPFC））通过选择性下调活动来调节目标导向/习惯性决策平衡 习惯性区域（壳核和辅助运动区）。在强迫症中，GD和GD之间存在不平衡， 和HB动作选择有利于HB动作选择。该项目旨在探索神经行为 这种仲裁机制的特点及其与强迫症行为和临床表型的关系 通过应用认知神经科学、基于临床任务的fMRI和经颅直流电刺激（tDCS） 接近。患有强迫症的成年人和健康对照组参与者在接受扫描时将执行两项任务， 当他们在扫描仪外的左侧ilPFC上接受抑制性、兴奋性和假tDCS时：I）a 决策任务，其中GD和HB策略竞争控制动作选择和II）临床 相关症状激发-回避任务，其中将模拟回避决策。该项目的 研究目的是：1）探讨GD、HB和仲裁区的神经活动和仲裁习惯性 强迫症中的电路连接; 2）检查行为表现的测量之间的关联， 仲裁的神经活动和连接，和强迫症的临床症状;和3）调查的行为 在任务执行期间，tDCS在仲裁区域（左ilPFC）上的结果。