BACKGROUND Deep brain stimulation (DBS) of subcallosal cingulate cortex (SCC) is a promising investigational therapy for treatment-resistant depression (TRD). However, outcomes vary, likely due to suboptimal DBS placement. Ideal placement is proposed to stimulate 4 SCC white matter bundles; however, no quantitative data have linked activation of these target tracts to response. OBJECTIVE Here we used the volume of tissue activated (VTA) and probabilistic diffusion tensor imaging (DTI) to quantify tract activation relating to response. METHODS DTI was performed in 19 TRD patients who received SCC-DBS. We defined clinical response as >48% reduction from baseline in the Hamilton Depression Rating Scale. Bilateral VTAs were generated based on subject-specific stimulation parameters. Patient-specific tract maps emanating from the VTAs were calculated using whole-brain probabilistic DTI. The four target tracts were isolated using tract-specific quantification and examined for overlap with DBS activated tissue. RESULTS Medial frontal and temporal projections were stimulated in all responders at 6 and 12 months. Individual tract-based generalized linear mixed model analysis revealed a significant tract-by-response interaction at both 6 (F(1,135) = 3.828, p = 0.001) and 12 (F(1,135) = 5.688, p < 0.001) months, with post hoc tests revealing a response-related increase in cingulum activation at 6 months (t(135) = 2.418, p = 0.017) and decrease in forceps minor activation at 12 months (t(135) = -2.802, p = 0.006). CONCLUSIONS A wider profile of white matter tracts, particularly to the medial frontal, was associated with DBS response. Cingulum bundle stimulation may promote early response and excess stimulation of the forceps minor might be detrimental. Our work supports prospective patient-specific targeting to inform personalized DBS.

中文翻译：

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基于束的分析胼胝体下扣带回脑深部刺激治疗难治性抑郁症的目标参与


背景胼胝体下扣带皮层（SCC）的深部脑刺激（DBS）是治疗难治性抑郁症（TRD）的一种有前途的研究疗法。然而，结果各不相同，可能是由于 DBS 放置不理想所致。建议理想的放置位置以刺激 4 个 SCC 白质束；然而，没有定量数据将这些靶区的激活与反应联系起来。目的在这里，我们使用组织激活体积（VTA）和概率扩散张量成像（DTI）来量化与反应相关的纤维束激活。方法 对 19 名接受 SCC-DBS 的 TRD 患者进行 DTI。我们将临床反应定义为汉密尔顿抑郁评定量表中较基线降低 >48%。双侧 VTA 是根据受试者特定的刺激参数生成的。使用全脑概率 DTI 计算源自 VTA 的患者特异性神经束图。使用特定束的定量方法分离出四个目标束，并检查是否与 DBS 激活的组织重叠。结果 所有反应者的内侧额叶和颞叶投射在 6 个月和 12 个月时均受到刺激。基于个体区域的广义线性混合模型分析显示，在 6 个月（F(1,135) = 3.828，p = 0.001）和 12 个月（F(1,135) = 5.688，p < 0.001）时，区域与反应之间存在显着的相互作用，其中事后测试显示，6 个月时扣带回激活与反应相关增加（t(135) = 2.418，p = 0.017），12 个月时镊子轻微激活减少（t(135) = -2.802，p = 0.006）。结论 更广泛的白质束，特别是内侧额叶，与 DBS 反应相关。扣带束刺激可能会促进早期反应，而小镊子的过度刺激可能是有害的。 我们的工作支持前瞻性的患者特定目标，为个性化 DBS 提供信息。