Modulating prefrontal circuits underlying behavioral flexibility in OCD: a TMS study

调节强迫症行为灵活性背后的前额叶回路：一项 TMS 研究

• 批准号: 10548181
• 负责人: Sarah Lynn Garnaat
• 金额: $ 30.64万
• 依托单位: BUTLER HOSPITAL (PROVIDENCE, RI)
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548181
• 关键词: Acute; Affect; Anatomy; Anterior; Area; Award; Behavior; Behavior Control; Behavioral; Brain; Brain region; Centers of Research Excellence; Chronic; Clinical; Corpus striatum structure; Data Correlations; Development; Disease; Dorsal; Enrollment; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impairment; Individual; Intervention; Investigation; Knowledge; Measures; Mentors; Obsessive-Compulsive Disorder; Participant; Patients; Pattern; Performance; Play; Population; Prefrontal Cortex; Procedures; Process; Research; Research Project Grants; Rest; Reversal Learning; Role; System; Testing; Training; Transcranial magnetic stimulation; Translations; Treatment outcome; Ventral Striatum; Work; age group; behavior change; behavior prediction; behavioral impairment; behavioral outcome; brain based; cingulate cortex; cognitive control; cognitive task; compulsion; disorder control; flexibility; healthy volunteer; improved; neural; neural circuit; neural patterning; neuroimaging; neuropsychiatric disorder; neuropsychiatry; neuroregulation; recruit; repetitive transcranial magnetic stimulation; response

PROJECT SUMMARY/ABSTRACT The primary goal of this proposed COBRE Center for Neuromodulation Project is to elucidate neural circuits underlying impairments in behavioral flexibility in OCD, using transcranial magnetic stimulation as a probe of the system and fMRI to measure functional changes within neural circuitry implicated in behavioral (in)flexibility in obsessive-compulsive disorder (OCD). OCD is a chronic and impairing neuropsychiatric disorders associated with impairments in behavioral flexibility – most notably, the compulsions which are a hallmark of the disorder. Patients with OCD also show impaired behavioral flexibility on a range of experimental tasks (e.g., set-shifting, task-switching, reversal learning). Moreover, neuroimaging findings in OCD routinely show abnormal patterns of activation during tasks probing behavioral flexibility. The proposed research project will use slow frequency (1-Hz) rTMS to probe dysfunctional circuitry, targeting frontal pole, an area involved in higher level cognitive control processes which likely plays a key role in coordination between multiple neural circuits involved in behavioral flexibility and which shares structural and functional connections to circuitry implicated in behavioral inflexibility in OCD. We aim to test whether (1) slow frequency (1-Hz) rTMS to frontal pole can affect functional changes within circuits showing abnormal functioning during behavioral flexibility in OCD, (2) whether rTMS targeting this circuitry can affect behavioral changes in a population with deficits in behavioral flexibility, and (3) whether circuit functioning relates to behavioral performance following rTMS. While a number of studies have shown abnormal neural circuit functioning during behavioral flexibility tasks in OCD, to our knowledge, this will be the first to move beyond correlational findings to directly examine changes to circuit functioning following a probe of the system using TMS. The long-term goal of this work is to inform target identification for development of neurocircuit-based interventions which may improve treatment outcomes for those with OCD.

项目摘要/摘要 这个拟议的神经调节项目的索布雷鞋垫中心的主要目标是阐明神经回路 使用经颅磁刺激作为OCD行为灵活性的潜在障碍 系统和fMRI测量行为（in）灵活性实施的神经电路中功能变化 在强迫症（OCD）中。强迫症是一种慢性和损害神经精神疾病 与行为灵活性的损害相关 - 最值得注意的是，强迫是 疾病。强迫症患者在一系列实验任务上还显示出行为灵活性受损 （例如，设置变动，任务切换，逆转学习）。此外，OCD中的神经影像学发现常规显示 任务探测行为灵活性的任务过程中激活的异常模式。拟议的研究项目将 使用缓慢的频率（1-Hz）RTM探测功能失调的电路，针对额叶，涉及的区域 更高级别的认知控制过程可能在多个神经之间的协调中起关键作用 行为灵活性涉及的电路，并与电路具有结构和功能连接 在强迫症中实施的行为僵化。我们旨在测试（1）缓慢的频率（1-Hz）RTMS到正面 杆可以影响电路内的功能变化，显示在行为灵活性期间的功能异常 强迫症，（2）针对此电路的RTM是否会影响具有定义的人群的行为变化 行为灵活性，（3）电路功能是否与RTMS后的行为性能有关。 尽管许多研究表明在行为灵活性任务中的神经回路功能异常 据我们所知，强迫症将是第一个超越相关发现直接检查变化的人 通过使用TMS探测系统后的电路功能。这项工作的长期目标是告知 目标识别基于神经电路的干预措施的开发，这些干预措施可能会改善治疗 患有强迫症患者的结果。