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

项目摘要/摘要 这个拟议的科布雷神经调节中心项目的主要目标是阐明神经回路 强迫症患者潜在的行为灵活性障碍，使用经颅磁刺激作为探测 测量神经回路中与行为(In)灵活性有关的功能变化的系统和功能磁共振成像 患有强迫症(OCD)。强迫症是一种慢性的、严重的神经精神疾病。 与行为灵活性受损有关--最值得注意的是，强迫症是 这是一种混乱。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。 (例如，集合转换、任务转换、反转学习)。此外，强迫症的神经影像表现通常显示 在探测行为灵活性的任务期间，激活模式异常。拟议的研究项目将 使用慢频(1-Hz)rTMS探测功能失调的电路，瞄准额极，这是一个涉及 更高水平的认知控制过程可能在多个神经之间的协调中发挥关键作用 与行为灵活性有关的电路，并共享与电路的结构和功能连接 与强迫症的行为僵化有关。我们的目标是测试(1)慢频率(1-Hz)rTMS是否到额叶 杆子可以影响在行为灵活性期间显示异常功能的电路内的功能变化 强迫症，(2)靶向此回路的rTMS是否会影响在大脑中有缺陷的人群的行为改变 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神经回路功能异常 强迫症，据我们所知，这将是第一次超越相关发现直接检查变化 在使用TMS对系统进行探测后恢复电路功能。这项工作的长期目标是向 靶标识别用于开发可能改善治疗的基于神经回路的干预措施 强迫症患者的结果。

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.