自主边缘神经调节对纤维肌痛症具有有益的临床效果。
Volitional limbic neuromodulation exerts a beneficial clinical effect on Fibromyalgia.
机构信息
Sagol Brain Institute, Wohl Institute for Advanced Imaging, Tel-Aviv Sourasky Medical Centre, Tel-Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel-Aviv, Israel.
Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel; Department of Internal Medicine, Tel Aviv Sourasky Medical Centre, Tel-Aviv, Israel.
出版信息
Neuroimage. 2019 Feb 1;186:758-770. doi: 10.1016/j.neuroimage.2018.11.001. Epub 2018 Nov 5.
Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by reducing sleep disorder improving emotion regulation. We further expected that improved clinical status would correspond with successful training as indicated by improved down modulation of the Amygdala-EFP signal. Thirty-Four Fibromyalgia patients (31F; age 35.6 ± 11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions or sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion. REM latency and objective sleep quality index were robustly improved following the treatment course only in the real-neurofeedback group (time × group p < 0.05) and to a greater extent among good modulators (time × sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the neurofeedback training. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the real-neurofeedback group (time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures. Our findings suggest that Amyg-EFP-neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation treatment in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the substantial link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.
使用神经反馈进行自主神经调节已被证明是一种治疗涉及外周和中枢神经失调的慢性疾病的潜在方法。在这里,我们将神经反馈应用于患有纤维肌痛的患者 - 一种涉及睡眠障碍和情绪失调的慢性疼痛综合征。这些辅助症状会对疼痛产生放大效应,已知是由边缘活动增强介导的。为了以适合 EEG 神经反馈训练的可扩展方式可靠地探测边缘活动,我们利用杏仁核 - BOLD 信号的电指纹 (EFP) 模型(称为杏仁核 - EFP),该模型已在我们实验室中成功验证用于自主神经调节。我们预计,旨在调节边缘活动的杏仁核 EFP 神经反馈训练将通过改善睡眠障碍和情绪调节来改善纤维肌痛患者的慢性疼痛。我们进一步预计,临床状况的改善将与训练成功相对应,这表现为杏仁核 EFP 信号的下调得到改善。34 名纤维肌痛患者(31F;年龄 35.6 ± 11.82)参加了一项随机安慰剂对照试验,每两周进行一次杏仁核 EFP 神经反馈治疗或假神经反馈治疗(n = 9),总共持续五周。在训练后,根据神经反馈训练的成功情况,将真正的神经反馈组中的参与者分为良好(n = 13)或不良(n = 12)调节剂。在治疗前后,获得了自我报告的疼痛、抑郁、焦虑、疲劳和睡眠质量,以及客观的睡眠指数。在神经反馈训练完成后的长达三年内提供了长期的临床随访。只有在真正的神经反馈组中(时间×组 p <0.05),并且在良好的调节剂中更为明显(时间×亚组 p <0.05),治疗过程后 REM 潜伏期和客观睡眠质量指数得到了显著改善。在神经反馈训练结束时,自我报告的措施并未显示出特定的治疗反应。然而,随访评估显示,慢性疼痛和主观睡眠体验的延迟改善仅在真正的神经反馈组中可见(时间×组 p <0.05)。调节分析表明,在随访评估中对疼痛的持久临床影响可以通过训练后客观睡眠和主观影响测量的即时改善来预测。我们的研究结果表明,专门针对边缘活动下调的杏仁核 EFP 神经反馈为纤维肌痛患者提供了一种基于 EEG 的自主神经调节治疗的成功原则方法。重要的是,似乎通过其改善睡眠的即时效果,神经反馈训练诱导了慢性疼痛的目标主观症状的延迟减轻,远远超过了即时安慰剂效应。这种治疗慢性疼痛的间接方法反映了躯体和情感失调之间的实质性联系,这种联系可以通过神经反馈成功靶向。