Division of Neurosurgery, Department of Surgery, University Health Network and University of Toronto, Toronto, Canada.
Krembil Research Institute, University of Toronto, Toronto, Canada.
Brain. 2022 Jun 30;145(6):2214-2226. doi: 10.1093/brain/awab447.
Deep brain stimulation targeting the subcallosal cingulate area, a hub with multiple axonal projections, has shown therapeutic potential for treatment-resistant mood disorders. While subcallosal cingulate deep brain stimulation drives long-term metabolic changes in corticolimbic circuits, the brain areas that are directly modulated by electrical stimulation of this region are not known. We used 3.0 T functional MRI to map the topography of acute brain changes produced by stimulation in an initial cohort of 12 patients with fully implanted deep brain stimulation devices targeting the subcallosal cingulate area. Four additional subcallosal cingulate deep brain stimulation patients were also scanned and employed as a validation cohort. Participants underwent resting state scans (n = 78 acquisitions overall) during (i) inactive deep brain stimulation; (ii) clinically optimal active deep brain stimulation; and (iii) suboptimal active deep brain stimulation. All scans were acquired within a single MRI session, each separated by a 5-min washout period. Analysis of the amplitude of low-frequency fluctuations in each sequence indicated that clinically optimal deep brain stimulation reduced spontaneous brain activity in several areas, including the bilateral dorsal anterior cingulate cortex, the bilateral posterior cingulate cortex, the bilateral precuneus and the left inferior parietal lobule (PBonferroni < 0.0001). Stimulation-induced dorsal anterior cingulate cortex signal reduction correlated with immediate within-session mood fluctuations, was greater at optimal versus suboptimal settings and was related to local cingulum bundle engagement. Moreover, linear modelling showed that immediate changes in dorsal anterior cingulate cortex, posterior cingulate cortex and precuneus activity could predict individual long-term antidepressant improvement. A model derived from the primary cohort that incorporated amplitude of low-frequency fluctuations changes in these three areas (along with preoperative symptom severity) explained 55% of the variance in clinical improvement in that cohort. The same model also explained 93% of the variance in the out-of-sample validation cohort. Additionally, all three brain areas exhibited significant changes in functional connectivity between active and inactive deep brain stimulation states (PBonferroni < 0.01). These results provide insight into the network-level mechanisms of subcallosal cingulate deep brain stimulation and point towards potential acute biomarkers of clinical response that could help to optimize and personalize this therapy.
针对扣带回下侧区域的深部脑刺激作为一种治疗抵抗性情绪障碍的治疗方法具有很大的潜力，因为该区域是一个具有多个轴突投射的枢纽。虽然扣带回下侧深部脑刺激可驱动皮质边缘回路的长期代谢变化，但目前尚不清楚该区域电刺激直接调节哪些脑区。我们使用 3.0T 功能磁共振成像技术，对最初的 12 名接受全植入式深部脑刺激装置靶向扣带回下侧区域的患者的急性脑变化进行刺激定位。另外 4 名扣带回下侧深部脑刺激患者也进行了扫描，并作为验证队列。参与者在静息状态下接受了扫描（总共 78 次采集），分别在（i）深部脑刺激不活跃期间；（ii）临床最佳深部脑刺激活跃期间；（iii）深部脑刺激不活跃期间。所有扫描均在单次 MRI 会话中进行，每个序列之间间隔 5 分钟洗脱期。对每个序列的低频波动幅度进行分析表明，临床最佳深部脑刺激降低了几个区域的自发性脑活动，包括双侧背侧前扣带回皮质、双侧后扣带回皮质、双侧楔前叶和左侧下顶叶（PBonferroni < 0.0001）。刺激诱导的背侧前扣带回皮质信号减少与即时会话内情绪波动相关，在最佳状态下比在次佳状态下更明显，与局部扣带束参与相关。此外，线性模型显示，背侧前扣带皮质、后扣带皮质和楔前叶活动的即时变化可以预测个体的长期抗抑郁改善。从主要队列中得出的一个模型，该模型纳入了这些三个区域的低频波动幅度变化（以及术前症状严重程度），可以解释该队列中临床改善的 55%的方差。相同的模型还解释了验证队列中 93%的方差。此外，所有三个脑区在主动和不活跃深部脑刺激状态之间的功能连接都发生了显著变化（PBonferroni < 0.01）。这些结果提供了关于扣带回下侧深部脑刺激的网络水平机制的见解，并指出了潜在的急性临床反应生物标志物，这可能有助于优化和个性化这种治疗。
