OBJECTIVES Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) is an emerging treatment for multiple brain diseases, including the drug-resistant epilepsy Lennox-Gastaut syndrome (LGS). We aimed to improve neurosurgical targeting of the CM by: (1) developing a structural MRI approach for CM visualisation, (2) identifying the CM's neurophysiological characteristics using microelectrode recordings (MERs) and (3) mapping connectivity from CM-DBS sites using functional MRI (fMRI). METHODS 19 patients with LGS (mean age=28 years) underwent presurgical 3T MRI using magnetisation-prepared 2 rapid acquisition gradient-echoes (MP2RAGE) and fMRI sequences; 16 patients proceeded to bilateral CM-DBS implantation and intraoperative thalamic MERs. CM visualisation was achieved by highlighting intrathalamic borders on MP2RAGE using Sobel edge detection. Mixed-effects analysis compared two MER features (spike firing rate and background noise) between ventrolateral, CM and parafasicular nuclei. Resting-state fMRI connectivity was assessed using implanted CM-DBS electrode positions as regions of interest. RESULTS The CM appeared as a hyperintense region bordering the comparatively hypointense pulvinar, mediodorsal and parafasicular nuclei. At the group level, reduced spike firing and background noise distinguished CM from the ventrolateral nucleus; however, these trends were not found in 20%-25% of individual MER trajectories. Areas of fMRI connectivity included basal ganglia, brainstem, cerebellum, sensorimotor/premotor and limbic cortex. CONCLUSIONS In the largest clinical trial of DBS undertaken in patients with LGS to date, we show that accurate targeting of the CM is achievable using 3T MP2RAGE MRI. Intraoperative MERs may provide additional localising features in some cases; however, their utility is limited by interpatient variability. Therapeutic effects of CM-DBS may be mediated via connectivity with brain networks that support diverse arousal, cognitive and sensorimotor processes.

中文翻译：

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靶向着丝粒丘脑丘脑核以进行深部脑刺激。

目标着丝粒体丘脑核（CM）的深部脑刺激（DBS）是一种针对多种脑部疾病的新兴治疗方法，包括耐药性癫痫性伦诺克斯-盖斯托综合征（LGS）。我们旨在通过以下方式改善CM的神经外科靶向性：（1）开发用于CM可视化的结构性MRI方法；（2）使用微电极记录（MER）识别CM的神经生理特征；（3）使用功能映射CM-DBS站点的连通性MRI（fMRI）。方法对19例LGS患者（平均年龄为28岁）进行了3T MRI检查，该检查采用了磁化准备的2次快速采集梯度回波（MP2RAGE）和fMRI序列。16例患者进行了双侧CM-DBS植入和术中丘脑MER。CM可视化是通过使用Sobel边缘检测在MP2RAGE上突出丘脑内边界来实现的。混合效应分析比较了腹侧，CM和筋膜旁核之间的两种MER特征（峰值发射率和背景噪声）。使用植入的CM-DBS电极位置作为关注区域来评估静止状态fMRI的连通性。结果CM表现为一个高强度区域，与相对低点的髓核，中嗅核和筋膜旁核相邻。在组水平上，减少的尖峰发射和背景噪声使CM与腹外侧核区分开。然而，在个体MER轨迹的20％-25％中未发现这些趋势。功能磁共振成像连接的区域包括基底神经节，脑干，小脑，感觉运动/前运动和边缘皮质。结论在迄今为止对LGS患者进行的DBS的最大临床试验中，我们表明使用3T MP2RAGE MRI可以实现CM的精确靶向。术中MER在某些情况下可能会提供其他定位功能。但是，它们的效用受到患者间差异的限制。CM-DBS的治疗作用可通过与支持各种唤醒，认知和感觉运动过程的脑网络的连通性来介导。