Objective

Deep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD.

Methods

We performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset.

Results

Probabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets.

Conclusions

Our results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.

中文翻译：

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深部脑刺激治疗难治性抑郁症的连接组学分析

客观的

十多年来，深部脑刺激（DBS）一直被用作治疗难治性抑郁症（TRD）的最后手段。许多 DBS 靶标已被提出并进行了临床测试，但潜在的回路机制仍不清楚。发现 DBS 靶标激活的白质束 (WMT) 可能会提供有关调节 DBS 改善 TRD 功效的电路基质的重要信息。

方法

我们使用人类连接组项目数据集中 100 名健康志愿者的扩散磁共振成像数据进行概率纤维束成像，以分析针对当前用于 TRD 的 DBS 目标的刺激的结构连接模式。我们生成了平均和二元纤维分布图，并计算了数据集中 WMT 流线的数量。

结果

概率跟踪结果表明，不同 DBS 目标的激活表现出重叠但相当不同的途径的调节。DBS 目标根据主要调节的 WMT 和大脑区域分为 4 组：皮质、纹状体、丘脑和内侧前脑束。我们的数据还显示，布罗德曼 10 区和杏仁核是与所有 DBS 目标相关的枢纽结构。

结论

我们的结果共同表明，DBS 目标的独特机制意味着未来 DBS 治疗 TRD 的个体化目标选择和制定。Brodmann 10 区和杏仁核的调节可能对于 DBS 介导的 TRD 治疗效果至关重要。