Deep brain stimulation (DBS) is a promising treatment option for severe refractory major depressive disorder (MDD) [1,2]. The most common neural targets for DBS in MDD are the subcallosal cingulate cortex (SCC) and the ventral capsule/ventral striatum (VC/VS) [3e5]. The long-term clinical response after DBS to these targets has been characterized as a gradual improvement in mood, with >40% of patients reaching a responder status by 1 year [3,4]. Recently, the superolateral branch of the medial forebrain bundle (slMFB) was identified as a novel DBS target for MDD [6]. Unlike the SCC and VC/VS, the slMFB can only be identified using diffusion magnetic resonance imaging (dMRI) [7]. The slMFB is an ascending white-matter tract containing the dopaminergic fibers of the meso-limbic and meso-cortical reward pathways [8]. Two centers have reported extremely favourable rapid results following DBS of the slMFB ( 50% responder status within 1 week, 80% responder status by 1 year) [8,9]. In this report, we outline our failed attempt to replicate these findings. Two patients with severe MDD underwent DBS to the slMFB (for inclusion/exclusion criteria see trial registry: NCT04009928). Both patients were males (ages 55,62) with a long-standing history of anhedonic MDD, who had failed numerous trials of pharmacotherapy, psychotherapy, and electroconvulsive therapy. The slMFB was targeted using pre-operative structural and diffusionweighted MRI scans, as previously reported [8,9]. A 3mm spherical region of interest (ROI) was placed in the midbrain, used as a seed to perform tractography (http://dsi-studio.labsolver.org/), and manually adjusted to maximize contact with the slMFB (Fig. 1). Coordinates of the inferior-medial aspect of the ROI was used as the target for DBS. DBS electrodes (Medtronic, 3389) were implanted with the patients awake but sedated. Intraoperative stimulation at the deepest contacts revealed diplopia but no autonomic changes. Patient 1 experienced a transient arousal/appetitive response during right sided test-stimulation, but this could not be re-captured on repeat testing. Under general anesthetic, the electrodes were connected to the implantable pulse generator (Medtronic, Activa PC). Electrode placement was verified with a postoperative MRI. Stimulation was initiated at 2 weeks postoperatively and adjusted biweekly. Programming began at 1.5V, 60ms, and 130Hz (bipolar) and was increased systematically by 0.5V biweekly, until persistent diplopia necessitated moving to other contacts. After 2-4-week trials of bipolar stimulation at each contact, monopolar stimulation was also tested. In a few instances, patients reported transient improvements in mood following stimulation change,

中文翻译：

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抑郁症对内侧前脑束深部脑刺激缺乏临床反应

脑深部电刺激 (DBS) 是重度难治性重度抑郁症 (MDD) 的一种有前景的治疗选择 [1,2]。MDD 中 DBS 最常见的神经目标是胼胝体扣带回皮层 (SCC) 和腹侧囊/腹侧纹状体 (VC/VS) [3e5]。DBS 后对这些目标的长期临床反应的特点是情绪的逐渐改善，> 40% 的患者在 1 年内达到反应状态 [3,4]。最近，内侧前脑束的上外侧分支 (slMFB) 被确定为 MDD 的新 DBS 目标 [6]。与 SCC 和 VC/VS 不同，slMFB 只能使用扩散磁共振成像 (dMRI) [7] 来识别。slMFB 是一种上升的白质束，包含中边缘和中皮层奖励通路的多巴胺能纤维 [8]。两个中心报告了 slMFB 的 DBS 后非常有利的快速结果（1 周内 50% 的反应状态，1 年内 80% 的反应状态）[8,9]。在本报告中，我们概述了重复这些发现的失败尝试。两名患有严重 MDD 的患者在 slMFB 中接受了 DBS（纳入/排除标准参见试验注册：NCT04009928）。两名患者均为男性（55,62 岁），有长期无快感 MDD 病史，多次尝试药物治疗、心理治疗和电休克治疗均失败。slMFB 的目标是使用术前结构和扩散加权 MRI 扫描，如先前报道的 [8,9]。一个 3mm 的球形感兴趣区域 (ROI) 被放置在中脑中，用作执行牵引成像的种子 (http://dsi-studio.labsolver.org/)，并手动调整以最大限度地与 slMFB 接触（图 1）。ROI 的下内侧坐标用作 DBS 的目标。DBS 电极（Medtronic，3389）在患者清醒但镇静的情况下植入。最深接触处的术中刺激显示复视，但没有自主神经变化。患者 1 在右侧测试刺激期间经历了短暂的唤醒/食欲反应，但无法在重复测试中重新捕获。在全身麻醉下，电极连接到植入式脉冲发生器（美敦力，Activa PC）。电极放置通过术后 MRI 验证。刺激在术后 2 周开始并每两周调整一次。编程开始于 1.5V、60ms 和 130Hz（双极），并且每两周系统地增加 0.5V，直到持续性复视需要转移到其他接触者为止。在每次接触的双极刺激试验 2-4 周后，还测试了单极刺激。在少数情况下，患者报告刺激变化后情绪暂时改善，