针对强迫症的深部脑刺激的统一功能网络靶点。
A Unified Functional Network Target for Deep Brain Stimulation in Obsessive-Compulsive Disorder.
机构信息
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany.
Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany; Charité - Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, Berlin, Germany; Berlin School of Mind and Brain, Faculty of Philosophy, Humboldt-Universität zu Berlin, Berlin, Germany.
出版信息
Biol Psychiatry. 2021 Nov 15;90(10):701-713. doi: 10.1016/j.biopsych.2021.04.006. Epub 2021 Apr 20.
BACKGROUND
Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks.
METHODS
First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants.
RESULTS
While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets.
CONCLUSIONS
Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected-regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.
背景
针对难治性强迫症(OCD),已有多种深部脑刺激(DBS)靶点被提出。在此,我们探究了不同靶点的刺激效果是否通过一个共同或多个分离的功能脑网络来介导。
方法
首先,对来自接受内囊前肢或丘脑底核区 DBS 的 4 个 OCD 患者队列(N=50)的活跃电极进行种子点分析,采用 leave-one-cohort-out 和 leave-one-patient-out 设计计算并交叉验证最佳功能连接图谱,以实现耶鲁-布朗强迫量表(Yale-Brown Obsessive Compulsive Scale)评分的最大改善。其次,我们得出了最优的靶向特异性连接模式,以确定对两个靶点的临床结果都具有预测性的大脑区域,以及对任一靶点具有预测性的其他区域。功能连接使用来自 1000 名健康参与者的静息态功能磁共振成像数据进行定义。
结果
尽管最佳功能连接图谱显示了靶点之间的共性和差异,但在 OCD 队列和靶点之间具有稳健的临床改善的交叉预测,提示存在一个共享网络。与岛叶、前扣带回皮质和楔前叶等其他区域的连接具有预测性,而与刺激靶点无关。与这些具有共同预测性的区域具有最大连接的区域包括岛叶、额上回、前扣带回皮质和前丘脑,以及原始的立体定向靶点。
结论
从不同的靶点确定 DBS 调节 OCD 的网络,确定了一组与 DBS 电极具有最佳结果相关的大脑区域,无论靶点选择如何。基于这些结果,我们确定了一些潜在的大脑区域,这些区域可能会为强迫症提供更多或替代的神经调节靶点。