Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia.
Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia.
J Neurophysiol. 2019 Sep 1;122(3):1023-1035. doi: 10.1152/jn.00875.2018. Epub 2019 Jul 17.
Subcallosal cingulate cortex deep brain stimulation (SCC-DBS) is an experimental therapy for treatment-resistant depression (TRD). Refinement and optimization of SCC-DBS will benefit from increased study of SCC electrophysiology in context of ongoing high-frequency SCC-DBS therapy. The study objective was a 7-mo observation of frequency-domain 1/ slope in off-stimulation local field potentials (SCC-LFPs) alongside standardized measurements of depression severity in 4 patients undergoing SCC-DBS. SCC was implanted bilaterally with a combined neurostimulation-LFP recording system. Following a 1-mo off-stimulation postoperative phase with multiple daily recordings, patients received bilateral SCC-DBS therapy (130 Hz, 90 μs) and weekly resting-state SCC-LFP recordings over a 6-mo treatment phase. 1/ slopes for each time point were estimated via linear regression of log-transformed Welch periodograms. General linear mixed-effects models were constructed to estimate pretreatment sources of 1/ slope variance, and 95% bootstrap confidence intervals were constructed to estimate treatment phase 1/ slope association with treatment response (50% decrease in preimplantation symptom severity). Results show the time of recording was a prominent source of pretreatment 1/ slope variance bilaterally, with increased 1/ slope magnitude observed during night hours (2300-0659). Increase in right 1/ slope was observed in the setting of treatment response, with bootstrap analysis supporting this observation in 3 of 4 subjects. We conclude that 1/ slope can be measured longitudinally in a combined SCC-DBS/LFP recording system and likely conforms to known 1/ circadian variability. The preliminary evidence of 1/ slope increase during treatment response suggests a potential utility as a candidate biomarker for ongoing development of adaptive TRD-neuromodulation strategies. In four patients with treatment-resistant depression undergoing therapeutic deep brain stimulation (DBS), we present the first longitudinal observations of local field potentials (LFP) from the subcallosal cingulate region outside the postoperative period. Specifically, our results demonstrate that frequency-domain 1/ activity is measurable in a combined DBS-LFP recording system and that right hemisphere recordings appear sensitive to mood state, thus suggesting a potential readout suitable for consideration in ongoing efforts to develop adaptive DBS delivery systems.
扣带皮层下脑刺激（SCC-DBS）是一种治疗难治性抑郁症（TRD）的实验性疗法。SCC-DBS 的改进和优化将受益于对 SCC 电生理学的深入研究，以便在持续的高频 SCC-DBS 治疗的背景下进行。研究目的是对 4 名接受 SCC-DBS 的患者进行为期 7 个月的观察，在停止刺激期间记录局部场电位（SCC-LFP）的频域 1/斜率，并结合抑郁严重程度的标准化测量。SCC 双侧植入神经刺激-LFP 记录系统。在 1 个月的无刺激术后阶段进行多次每日记录后，患者接受双侧 SCC-DBS 治疗（130 Hz，90 μs），并在 6 个月的治疗阶段每周进行静息状态 SCC-LFP 记录。通过对数变换的 Welch 周期图的线性回归估计每个时间点的 1/斜率。构建了广义线性混合效应模型来估计 1/斜率方差的预处理来源，并构建了 95%的自举置信区间来估计治疗阶段 1/斜率与治疗反应（植入前症状严重程度降低 50%）的相关性。结果表明，记录时间是双侧预处理 1/斜率方差的主要来源，夜间（2300-0659）观察到 1/斜率幅度增加。在治疗反应的背景下观察到右侧 1/斜率增加，bootstrap 分析支持 4 名患者中的 3 名。我们得出结论，1/斜率可以在 SCC-DBS/LFP 记录系统中进行纵向测量，并且可能符合已知的 1/circadian 变异性。在治疗反应期间增加 1/斜率的初步证据表明，它作为正在开发的适应性 TRD-神经调节策略的候选生物标志物具有潜在的用途。在 4 名接受治疗性深部脑刺激（DBS）治疗的难治性抑郁症患者中，我们首次在术后期间以外的扣带皮层下区域观察到局部场电位（LFP）的纵向观察。具体而言，我们的结果表明，频域 1/活动可在 DBS-LFP 联合记录系统中测量，并且右半球记录对情绪状态敏感，因此表明潜在的读出适合考虑正在开发的适应性 DBS 输送系统。
