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

项目总结/摘要 这个建议的COBRE神经调节中心项目的主要目标是阐明神经回路 强迫症中行为灵活性的潜在损害，使用经颅磁刺激作为 该系统和功能磁共振成像测量神经回路内的功能变化，涉及行为（不）灵活性 强迫症（OCD）。强迫症是一种慢性损害性神经精神障碍 与行为灵活性受损有关-最值得注意的是，强迫症是 紊乱强迫症患者在一系列实验任务中也表现出行为灵活性受损 (e.g.,集合转移、任务转换、逆向学习）。此外，强迫症的神经影像学结果通常显示， 在探索行为灵活性的任务中激活的异常模式。拟议的研究项目将 使用慢频率（1 Hz）rTMS探测功能障碍的电路，目标是额极，一个涉及 更高层次的认知控制过程可能在多个神经元之间的协调中起着关键作用。 参与行为灵活性的电路，与电路共享结构和功能连接 与强迫症的行为相似性有关我们的目的是测试（1）慢频率（1-Hz）rTMS是否对额叶 极点可以影响电路内的功能变化，在行为灵活性期间显示异常功能， 强迫症，（2）针对该回路的rTMS是否可以影响缺乏以下功能的人群的行为变化： 行为灵活性，以及（3）电路功能是否与rTMS后的行为表现有关。 虽然许多研究表明，在行为灵活性任务中， 强迫症，据我们所知，这将是第一个超越相关性的发现，直接检查变化 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 用于开发可改善治疗的基于神经回路的干预措施的目标识别 对于那些有强迫症的人来说。

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.