难治性强迫症脑深部电刺激治疗的电生理机制及预后因素研究

Obsessive compulsive disorder (OCD) is a common and severe mental illness with a 0.8%-3% incidence rate, due to its early age of onset and chronic course with many largely unmet needs, is particularly devastating. For those(10%) with poor response to the most efficacious treatments, neuromodulation therapy such as deep brain stimulation(DBS) are considered. Deep brain stimulation of ventral internal capsule and ventral striatum (VC/VS) including nucleus accumbens targets, is a reversible neurosurgical procedure which has been approved by American and European Food and Drug Administration with 50%-75% efficiency. However, research is needed to understand disease neurophysiology, DBS parameter setting and mechanisms of successful DBS treatment. Our team which includes Shanghai RuiJin Hospital, Beijing Sixth Hospital and Institute of Neuroscience, will use electrophysiological, neuroimging and other features to identify neuronal signatures (biomarkers) in refractory OCD patients.They are useful to 1) identify sub-territories to refine the targeted region DBS ; 2)identify disease signatures that allow verification of specific target engagement in therapy (stimulation) ; and 3) identify an association with neuronal disease signatures and successful DBS treatment. Fundamental knowledge will be gained about the neuronal characteristic of nucleus accumbens that will inform development of therapies. More broadly, this information will inform DBS of VC/VS currently being investigating for the treatment of depression, anorexia, and opioid dependence.

强迫症是常见的严重精神疾病，发病率0.8%-3%，由于发病年龄早和慢性病程，是青壮年全球疾病负担最大的疾病。药物治疗和认知行为治疗部分有效（约60%），约10%患者在现有疗法下缓解不完全并残留严重失能症状，对难治性患者可使用脑深部电刺激治疗，该疗法已获得欧盟、美国等地药监局批准临床应用，疗效约50%-75%，然而缺乏疗效预后指标，电刺激参数调节复杂。本项目联合上海瑞金医院的精神障碍神经调控手术的专长、北医六院精神病学、神经影像学专长与中科院神经所电生理学专长，将采用国际难治性强迫症入排标准，通过术前检测临床及影像指标、记录脑深部结构的电生理活动并随访疗效。该工作有望提供强迫症腹侧纹状体/内囊前肢神经生理学特征，结果将阐明疾病病理学、寻找预后生物标记物、优化刺激参数设置并最终促进新治疗的形成，以治疗其他类似手术干预的疾病，如抑郁症、厌食症、药物依赖等。

腹侧内囊/腹侧纹状体脑深部电刺激治疗难治性强迫症（OCD）已获得欧盟、美国等地药监局批准临床应用，但电刺激参数调节复杂、缺乏疗效预后指标。我们拟采用影像、认知和电生理技术阐明强迫症疾病病理学。我们发现，与健康对照相比，OCD患者具有更高估计的GANB水平和更高的GABA与谷氨酸比，在执行控制上能力相当。OCD患者在腹侧内囊前肢射频消融术治疗后，腹侧纹状体/伏隔核与背侧前扣带回（dACC）的功能性连接减弱，功能连接的变化与强迫症严重程度YBOCS分数的改变有显著相关。此外，术前背侧尾状核与dACC的功能连接强度在治疗无效组中的功能连接强度更强，能预测YBOCS分数的改变。我们还发现精神疾病中额叶皮层-缰核网络中theta/alpha波段同步性的增加与情绪效价相关，但与刺激的唤起得分无关。