Kibleur A, Gras-Combe G, Benis D, Bastin J, Bougerol T, Chabardès S, Polosan M, David O
Université Grenoble Alpes, Grenoble, France.
Inserm, U1216, Grenoble Institut des Neurosciences, Grenoble, France.
Transl Psychiatry. 2016 Oct 18;6(10):e922. doi: 10.1038/tp.2016.192.
High-frequency deep brain stimulation of the subthalamic nucleus can be used to treat severe obsessive-compulsive disorders that are refractory to conventional treatments. The mechanisms of action of this approach possibly rely on the modulation of associative-limbic subcortical-cortical loops, but remain to be fully elucidated. Here in 12 patients, we report the effects of high-frequency stimulation of the subthalamic nucleus on behavior, and on electroencephalographic responses and inferred effective connectivity during motor inhibition processes involved in the stop signal task. First, we found that patients were faster to respond and had slower motor inhibition processes when stimulated. Second, the subthalamic stimulation modulated the amplitude and delayed inhibition-related electroencephalographic responses. The power of reconstructed cortical current densities decreased in the stimulation condition in a parietal-frontal network including cortical regions of the inhibition network such as the superior parts of the inferior frontal gyri and the dorsolateral prefrontal cortex. Finally, dynamic causal modeling revealed that the subthalamic stimulation was more likely to modulate efferent connections from the basal ganglia, modeled as a hidden source, to the cortex. The connection from the basal ganglia to the right inferior frontal gyrus was significantly decreased by subthalamic stimulation. Beyond motor inhibition, our study thus strongly suggests that the mechanisms of action of high-frequency subthalamic stimulation are not restricted to the subthalamic nucleus, but also involve the modulation of distributed subcortical-cortical networks.
丘脑底核高频深部脑刺激可用于治疗对传统治疗无效的严重强迫症。这种治疗方法的作用机制可能依赖于对联合-边缘系统皮层下-皮层环路的调节,但仍有待充分阐明。在此,我们报告了12例患者中,丘脑底核高频刺激对行为、脑电图反应以及在停止信号任务中运动抑制过程中推断的有效连接性的影响。首先,我们发现患者在受到刺激时反应更快,运动抑制过程更慢。其次,丘脑底核刺激调节了与抑制相关的脑电图反应的幅度并延迟了其出现。在包括抑制网络皮层区域(如下额回上部和背外侧前额叶皮层)的顶叶-额叶网络中,刺激条件下重建的皮层电流密度功率降低。最后,动态因果模型显示,丘脑底核刺激更有可能调节从作为隐藏源建模的基底神经节到皮层的传出连接。丘脑底核刺激使从基底神经节到右下额回的连接显著减少。因此,除了运动抑制外,我们的研究强烈表明,丘脑底核高频刺激的作用机制不仅限于丘脑底核,还涉及对分布式皮层下-皮层网络的调节。