Derksen Maik, Zuidinga Birte, van der Veer Marijke, Rhemrev Valerie, Jolink Linda, Reneman Liesbeth, Nederveen Aart, Forstmann Birte, Feenstra Matthijs, Willuhn Ingo, Denys Damiaan
The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Psychiatry, Amsterdam University Medical Centers (location AMC), University of Amsterdam, Amsterdam, The Netherlands.
The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Psychiatry Res Neuroimaging. 2023 Apr;330:111611. doi: 10.1016/j.pscychresns.2023.111611. Epub 2023 Feb 9.
Deep brain stimulation (DBS) is an established neuromodulatory intervention against otherwise treatment-refractory obsessive-compulsive disorder (OCD). Several DBS targets, all of which are part of brain networks connecting basal ganglia and prefrontal cortex, alleviate OCD symptoms. Stimulation of these targets is thought to unfold its therapeutic effect by modulation of network activity through internal capsule (IC) connections. Research into DBS-induced network changes and the nature of IC-related effects of DBS in OCD is needed to further improve DBS. Here, we studied the effects of DBS at the ventral medial striatum (VMS) and IC on blood-oxygen level dependent (BOLD) responses in awake rats using functional magnetic resonance imaging (fMRI). BOLD-signal intensity was measured in five regions of interest (ROIs): medial and orbital prefrontal cortex, nucleus accumbens (NAc), IC area, and mediodorsal thalamus. In previous rodent studies, stimulation at both target locations resulted in a reduction of OCD-like behavior and activation of prefrontal cortical areas. Therefore, we hypothesized that stimulation at both targets would result in partially overlapping BOLD responses. Both differential and overlapping activity between VMS and IC stimulation was found. Stimulating the caudal part of the IC resulted in activation around the electrode, while stimulating the rostral part of the IC resulted in increased cross-correlations between the IC area, orbitofrontal cortex, and NAc. Stimulation of the dorsal part of the VMS resulted in increased activity in the IC area, suggesting this area is activated during both VMS and IC stimulation. This activation is also indicative of VMS-DBS impacting corticofugal fibers running through the medial caudate into the anterior IC, and both VMS and IC DBS might act on these fibers to induce OCD-reducing effects. These results show that rodent fMRI with simultaneous electrode stimulation is a promising approach to study the neural mechanisms of DBS. Comparing the effects of DBS in different target areas has the potential to improve our understanding of the neuromodulatory changes that take place across various networks and connections in the brain. Performing this research in animal disease models will lead to translational insights in the mechanisms underlying DBS, and can aid improvement and optimization of DBS in patient populations.
深部脑刺激（DBS）是一种针对其他治疗方法难治的强迫症（OCD）的既定神经调节干预措施。几个DBS靶点，均为连接基底神经节和前额叶皮层的脑网络的一部分，可缓解强迫症症状。这些靶点的刺激被认为是通过内囊（IC）连接调节网络活动来发挥其治疗作用。需要对DBS诱导的网络变化以及DBS在强迫症中与IC相关的效应的性质进行研究，以进一步改善DBS。在此，我们使用功能磁共振成像（fMRI）研究了腹内侧纹状体（VMS）和IC处的DBS对清醒大鼠血氧水平依赖性（BOLD）反应的影响。在五个感兴趣区域（ROI）测量了BOLD信号强度：内侧和眶前额叶皮层、伏隔核（NAc）、IC区域和背内侧丘脑。在先前的啮齿动物研究中，在两个靶点位置进行刺激均导致强迫症样行为减少以及前额叶皮层区域激活。因此，我们假设在两个靶点进行刺激会导致部分重叠的BOLD反应。发现了VMS和IC刺激之间的差异和重叠活动。刺激IC的尾部会导致电极周围激活，而刺激IC的头部会导致IC区域、眶额叶皮层和NAc之间的互相关性增加。刺激VMS的背部会导致IC区域活动增加，表明该区域在VMS和IC刺激期间均被激活。这种激活也表明VMS-DBS影响通过内侧尾状核进入前IC的皮质传出纤维，并且VMS和IC DBS可能作用于这些纤维以诱导强迫症减轻效应。这些结果表明，同时进行电极刺激的啮齿动物fMRI是研究DBS神经机制的一种有前景的方法。比较不同靶点区域的DBS效应有可能增进我们对大脑中各种网络和连接中发生的神经调节变化的理解。在动物疾病模型中进行这项研究将带来对DBS潜在机制转化性的见解，并有助于改善和优化针对患者群体的DBS。
