重复经颅磁刺激调控强迫症目标导向控制缺陷的机制研究

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique. The results of the efficacy studies of rTMS for OCD are inconsistent, which is related with the uncertainty of brain regions, cortical functions, neurotransmitters and cognitive functions referred to efficacious rTMS for OCD. The previous study found that the main changing of cognitive functions in OCD patients was the behavioral model from goal-directed control to habit formation, which was related with the overactivity of orbitofrontal cortex and caudate and might be modulated by rTMS. We found that OCD patients had overactivity of cortical function and decreased level of gamma-aminobutyric acid (GABA) in orbital frontal cortex (OFC) than the healthy controls. We assume that low frequency rTMS treatment which is applied to stimulate the OFC in OCD patients increase the GABA level in OFC, decrease the overactivity of orbitofrontal cortex and caudate, improve the deficit of goal-directed control and decrease the compulsivity. The project combines the techniques of behavioral tests, event-related functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS), uses the case control and randomized double-blind sham-controlled study to compare the level of goal-directed control, the neural function of orbitofrontal cortex-caudate circuit and the level of GABA in OFC between patients and healthy controls at baseline, in patients before and after low frequency rTMS treatment which is applied to stimulate the OFC and between patients after rTMS treatment and healthy controls. The proof of the hypothesis would clarify the mechanism of goal-directed control deficit in obsessive-compulsive disorder modulated by rTMS and provide the reference of developing the precision therapeutics.

重复经颅磁刺激（rTMS）是一种无创性神经调控技术，对强迫症（OCD）的疗效研究结果不一致。这和rTMS有效治疗OCD所涉及脑区、皮层功能、神经递质和认知功能不明有关。既往研究明确OCD主要认知功能改变是行为模式从目标导向控制向习惯转换，与眶额叶皮层-尾状核环路过度兴奋有关，可能受rTMS调控。我们发现OCD眶额叶皮层（OFC）过度兴奋和γ-氨基丁酸浓度下降。本研究假设低频rTMS刺激OCD的OFC，增加γ-氨基丁酸水平，降低OFC-尾状核环路功能，改善目标导向控制缺陷，减轻强迫行为。本项目结合行为学、任务态功能磁共振成像和磁共振波谱技术，采用病例对照和随机双盲伪刺激对照方法，比较OCD患者和健康对照、干预前后患者以及干预后患者与健康对照的目标导向控制程度、OFC-尾状核环路功能、OFCγ-氨基丁酸水平。假设的证明，可明确rTMS调控OCD目标导向控制缺陷的机制，为发展OCD精准治疗提供依据。

重复经颅磁刺激（rTMS）是一种无创性神经调控技术，对强迫症（OCD）的疗效研究结果不一致，与神经调控机制尚不明确有关。本研究结合行为学、功能磁共振成像和磁共振波谱等多模态影像学技术，采用病例对照和随机双盲伪刺激对照方法，比较OCD患者和健康对照、rTMS干预前后患者的目标导向控制程度、眶额叶（OFC）-尾状核环路功能、γ-氨基丁酸水平（GABA）。研究发现OCD患者存在目标导向控制缺陷，与强迫行为负相关，与过度兴奋的右侧OFC负相关，且眶额叶皮层GABA水平与双侧尾状核之间的功能连接（FC）值正相关；足强度足疗程低频rTMS治疗OCD是一种安全且可接受的治疗方法，能显著改善OCD患者的抑郁和焦虑症状，增加认知灵活性，改善目标导向控制缺陷，同时调控眶额叶皮层-尾状核环路功能。该假设的证明，可明确rTMS调控OCD目标导向控制缺陷的机制，为发展OCD精准治疗提供依据，也为OCD发病机制研究提供新的研究思路。