Department of Psychiatry, University of Calgary, Calgary, AB, Canada; Department of Clinical Neuroscience, University of Calgary, AB, Canada; Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, UT, USA; Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.
Brain Stimul. 2020 Jul-Aug;13(4):1094-1101. doi: 10.1016/j.brs.2020.03.006. Epub 2020 Mar 19.
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.
Here we used the volume of tissue activated (VTA) and probabilistic diffusion tensor imaging (DTI) to quantify tract activation relating to response.
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.
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).
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.
扣带回下皮质（SCC）的深部脑刺激（DBS）是一种有前途的治疗难治性抑郁症（TRD）的研究性治疗方法。 然而，结果各不相同，可能是由于 DBS 放置不理想。 建议理想的放置位置是刺激 4 个 SCC 白质束； 然而，尚无定量数据将这些目标束的激活与反应联系起来。
本研究使用激活的组织体积（VTA）和概率弥散张量成像（DTI）来量化与反应相关的束激活。
在 19 名接受 SCC-DBS 的 TRD 患者中进行了 DTI。 我们将 Hamilton 抑郁评定量表（HDRS）基线降低>48%定义为临床反应。 根据受试者特异性刺激参数生成双侧 VTA。 使用全脑概率 DTI 计算源自 VTA 的患者特异性束图。 使用束特异性量化方法分离出四个目标束，并检查它们与 DBS 激活组织的重叠。
在所有反应者中，6 个月和 12 个月时都刺激了内侧额和颞叶投射。 个体束基于广义线性混合模型分析在 6 个月（F（1，135）=3.828，p=0.001）和 12 个月（F（1，135）=5.688，p<0.001）时显示出束与反应之间的显著相互作用，事后检验显示 6 个月时扣带束激活与反应相关增加（t（135）=2.418，p=0.017），12 个月时小内囊束激活减少（t（135）= -2.802，p=0.006）。
更广泛的白质束谱，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，而过多刺激小内囊可能会产生不利影响。 我们的工作支持针对特定患者的前瞻性靶向，以提供个性化的 DBS。
