Background: Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. Methods: We performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. Results: No model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Conclusions: Patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

中文翻译：

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特定于患者的连接体模型与强迫症有关，但不能预测深部脑刺激的结果

背景：腹内侧囊/腹纹状体（VCVS）的深部脑刺激（DBS）是一种强迫症（OCD）的新兴治疗方法。最近，使用规范性连接体的多项研究已将DBS结局与特定白质束的刺激相关。这些研究没有测试这些相关性是否具有临床预测性，也没有应用生物标志物开发所必需的交叉验证方法。此外，他们没有考虑DBS患者与规范性连接套中使用的未诊断对照之间系统性差异的可能性。方法：我们对8例接受OCVS的VCVS DBS的患者进行了患者特异性扩散成像。我们描绘了通过VCVS将丘脑和丘脑下核（STN）连接到额叶前皮层的区域。然后，我们计算了各个患者的DBS设置可能激活了哪些管道。我们拟合了多种统计模型，以预测由于管道激活而导致的强迫症和抑郁症结局。我们进一步尝试预测轻度躁狂，这是一种VCVS DBS并发症。我们根据保留的测试集评估了所有模型的性能。结果：没有模型预测OCD反应，抑郁反应或轻度躁狂高于机会。系数检查在某种程度上支持了先前的报告，因为捕获投射到扣带回皮层的束与YBOCS和MADRS响应均相关。但是，与先前的报告相比，与STN连接的区域与响应没有可靠的关联。结论：特定于患者的影像学检查和指导性依从分析无法确定具有足够效果大小以推动临床决策或预测个体结局的体表学靶标。这些发现提示在解释规范性连接基因组研究的结果时要谨慎。