Hamani Clement, Davidson Benjamin, Corchs Felipe, Abrahao Agessandro, Nestor Sean M, Rabin Jennifer S, Nyman Alexander J, Phung Liane, Goubran Maged, Levitt Anthony, Talakoub Omid, Giacobbe Peter, Lipsman Nir
Sunnybrook Research Institute, Toronto, ON M4N3M5, Canada.
Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
Sci Adv. 2022 Dec 2;8(48):eadc9970. doi: 10.1126/sciadv.adc9970.
Deep brain stimulation (DBS) has been investigated for neuropsychiatric disorders. In this phase 1 trial, we treated four posttraumatic stress disorder (PTSD) patients with DBS delivered to the subgenual cingulum and the uncinate fasciculus. In addition to validated clinical scales, patients underwent neuroimaging studies and psychophysiological assessments of fear conditioning, extinction, and recall. We show that the procedure is safe and potentially effective (55% reduction in Clinical Administered PTSD Scale scores). Posttreatment imaging data revealed metabolic activity changes in PTSD neurocircuits. During psychophysiological assessments, patients with PTSD had higher skin conductance responses when tested for recall compared to healthy controls. After DBS, this objectively measured variable was significantly reduced. Last, we found that a ratio between recall of extinguished and nonextinguished conditioned responses had a strong correlation with clinical outcome. As this variable was recorded at baseline, it may comprise a potential biomarker of treatment response.
深部脑刺激（DBS）已被用于研究神经精神疾病。在这项1期试验中，我们对4名创伤后应激障碍（PTSD）患者进行了DBS治疗，刺激靶点为膝下扣带回和钩束。除了经过验证的临床量表外，患者还接受了神经影像学研究以及恐惧条件反射、消退和回忆的心理生理评估。我们发现该治疗方法是安全的且可能有效（临床管理PTSD量表评分降低了55%）。治疗后的影像学数据显示PTSD神经回路的代谢活动发生了变化。在心理生理评估期间，与健康对照组相比，PTSD患者在进行回忆测试时皮肤电导反应更高。DBS治疗后，这个客观测量的变量显著降低。最后，我们发现消退的条件反应与未消退的条件反应的回忆比率与临床结果密切相关。由于这个变量是在基线时记录的，它可能构成治疗反应的潜在生物标志物。
