Confirmatory Efficacy Clinical Trial of Amygdala Neurofeedback for Depression

摘要 多达三分之二的被诊断为严重抑郁障碍(MDD)的患者对标准药物没有反应 药物和心理干预，表明有必要开发新的治疗方法。减少 对积极刺激的反应性，以杏仁核对积极的自传体记忆回忆的低反应性为指标， 可能是一种干扰MDD康复的因果机制。先前的研究表明，那些 对抗抑郁药物的反应显示杏仁核对积极刺激的活性增加，即 与对照组没有区别，而那些没有反应的人没有表现出杏仁核活动的这种增加。 在几项小型研究中，我们已经表明MDD参与者能够增加他们的杏仁核反应 在通过实时功能磁共振神经反馈(rtfMRI-nf)训练进行积极记忆回忆期间，这一增加是 与抑郁症状的大幅快速减少有关。在这里，我们建议评估疗效 在一项大规模的验证性R01临床试验中进行了这种干预。N=200名MDD患者将被随机 在双盲条件下分配给杏仁核rtfMRI-nf干预组或对照rtfmri-nf组 干预，他们接受带轭的假神经反馈(他们看到的不是自己的大脑活动，而是 来自接受杏仁核rtfMRI-nf检查的另一名参与者的信号)。我们建议使用相同的 神经反馈范式与我们之前的研究一样，有一个关键的区别。而不是使用控制条件 这涉及到训练另一个大脑区域，我们将采用带轭的假对照组来演示 我们的发现对所使用的控制条件的类型是稳健的。此外，我们还打算确定我们是否 可以使用自我报告机制来评估谁可能需要建议的神经反馈干预，以及 他们是否有可能成功地使用它。最后，我们将与实施科学家合作，以获得 来自最终用户和临床医生的反馈，以了解背景对结果的影响并提高 干预可接受性。成功将证实一种新的非药物、非侵入性治疗MDD的方法 个人。

Abstract Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard pharmacological and psychological interventions, suggesting a need to develop novel therapeutics. Decreased reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical memory recall, may be a causal mechanism interfering with recovery from MDD. Previous work suggests that individuals who do respond to antidepressant medications show increased amygdala activity to positive stimuli that is indistinguishable from controls, while those who do not respond fail to show this increase in amygdala activity. In several small studies we have shown that MDD participants are able to increase their amygdala response during positive memory recall via real-time fMRI neurofeedback (rtfMRI-nf) training, and that this increase is associated with large and rapid reductions in depressive symptoms. Here, we propose to evaluate the efficacy of this intervention in a large-scale confirmatory R01 clinical trial. N=200 MDD individuals will be randomly assigned under double-blind conditions to the amygdala rtfMRI-nf intervention or to a control rtfMRI-nf intervention where they receive yoked sham neurofeedback (instead of their own brain activity they see the signal from another participant who underwent amygdala rtfMRI-nf). We propose to use the same neurofeedback paradigm as our prior studies, with one critical difference. Rather than using a control condition that involves training another brain region, we will adopt a yoked sham control group in order to demonstrate that our findings are robust to the type of control condition used. We additionally aim to determine whether we can use self-report mechanisms to assess who might need the proposed neurofeedback intervention and whether they are likely to be successful in using it. Finally, we will work with implementation scientists to obtain feedback from end-users and clinicians to understand contextual influences on outcomes and increase intervention acceptability. Success will confirm a new non-pharmacological, non-invasive intervention for MDD individuals.