Chen Xiaoyu, Wang Zhen, Lv Qian, Lv Qiming, van Wingen Guido, Fridgeirsson Egill Axfjord, Denys Damiaan, Voon Valerie, Wang Zheng
Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
Mol Psychiatry. 2022 Feb;27(2):1020-1030. doi: 10.1038/s41380-021-01358-w. Epub 2021 Oct 26.
Neurosurgical interventions including deep brain stimulation (DBS) and capsulotomy have been demonstrated effective for refractory obsessive-compulsive disorder (OCD), although treatment-shared/-specific network mechanisms remain largely unclear. We retrospectively analyzed resting-state fMRI data from three cohorts: a cross-sectional dataset of 186 subjects (104 OCD and 82 healthy controls), and two longitudinal datasets of refractory patients receiving ventral capsule/ventral striatum DBS (14 OCD) and anterior capsulotomy (27 OCD). We developed a machine learning model predictive of OCD symptoms (indexed by the Yale-Brown Obsessive Compulsive Scale, Y-BOCS) based on functional connectivity profiles and used graphic measures of network communication to characterize treatment-induced profile changes. We applied a linear model on 2 levels treatments (DBS or capsulotomy) and outcome to identify whether pre-surgical network communication was associated with differential treatment outcomes. We identified 54 functional connectivities within fronto-subcortical networks significantly predictive of Y-BOCS score in patients across 3 independent cohorts, and observed a coexisting pattern of downregulated cortico-subcortical and upregulated cortico-cortical network communication commonly shared by DBS and capsulotomy. Furthermore, increased cortico-cortical communication at ventrolateral and centrolateral prefrontal cortices induced by DBS and capsulotomy contributed to improvement of mood and anxiety symptoms, respectively (p < 0.05). Importantly, pretreatment communication of ventrolateral and centrolateral prefrontal cortices were differentially predictive of mood and anxiety improvements by DBS and capsulotomy (effect sizes = 0.45 and 0.41, respectively). These findings unravel treatment-shared and treatment-specific network characteristics induced by DBS and capsulotomy, which may facilitate the search of potential evidence-based markers for optimally selecting among treatment options for a patient.
神经外科干预措施,包括深部脑刺激(DBS)和内囊切开术,已被证明对难治性强迫症(OCD)有效,尽管治疗共享/特异性的网络机制在很大程度上仍不清楚。我们回顾性分析了来自三个队列的静息态功能磁共振成像(fMRI)数据:一个包含186名受试者(104名强迫症患者和82名健康对照)的横断面数据集,以及两个接受腹侧囊/腹侧纹状体DBS(14名强迫症患者)和前内囊切开术(27名强迫症患者)的难治性患者的纵向数据集。我们基于功能连接图谱开发了一个预测强迫症症状(由耶鲁-布朗强迫症量表,即Y-BOCS索引)的机器学习模型,并使用网络通信的图形测量来表征治疗引起的图谱变化。我们对治疗(DBS或内囊切开术)和结果应用了一个二级线性模型,以确定术前网络通信是否与不同的治疗结果相关。我们在额-皮质下网络中识别出54种功能连接,这些连接在3个独立队列的患者中显著预测Y-BOCS评分,并观察到DBS和内囊切开术共同具有的皮质-皮质下网络通信下调和皮质-皮质网络通信上调的共存模式。此外,DBS和内囊切开术分别在腹外侧和中央外侧前额叶皮质诱导的皮质-皮质通信增加,分别有助于改善情绪和焦虑症状(p < 0.05)。重要的是,腹外侧和中央外侧前额叶皮质的术前通信分别对DBS和内囊切开术改善情绪和焦虑具有不同的预测作用(效应大小分别为0.45和0.41)。这些发现揭示了DBS和内囊切开术诱导的治疗共享和治疗特异性网络特征,这可能有助于寻找潜在的循证标志物,以便为患者在治疗选择中进行最佳选择。