Amygdala rtfMRI Neurofeedback for Treatment Resistant 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，并将被视为治疗耐药(TR-MDD)。 对积极刺激的反应性降低，以杏仁核对积极自传性刺激的低反应性为指标 记忆回忆可能是干扰从TR-MDD恢复的一种原因机制。我们实验室以前的工作 提示对抗抑郁药物有反应的人表现出杏仁核活动增加， 与对照相比，与基线没有区别，而DR-MDD患者未能在 杏仁核活动。此外，我们还发现，MDD参与者(更广泛地说，不是具体的tr- MDD)确实能够通过实时功能磁共振成像在积极记忆回忆过程中增强他们的杏仁核反应 神经反馈(rtfMRI-nf)训练，这种增加与大量和快速的减少有关 抑郁症状。在这里，我们建议评估rtfmri-nf训练是否能增加杏仁核。 对积极记忆的反应可能是对TRMDD的一种干预。R61期间将涉及 干预措施的改进和机制的评估；N=40名TRMDD患者将经历5个杏仁核 Rtfmri-nf训练课程，我们将评估杏仁核活动的变化，目的是证实 患有tr-MDD的患者能够增加对积极记忆的杏仁核反应，并确定 足够的目标参与/杏仁核渐近线所需的最少训练课程数为 已到达。R33阶段将涉及与对照干预和评估的机械性比较 临床变化(包括作用持续时间)。N=60名tr-mdd个人将被随机分配到 杏仁核rtfMRI-nf干预或对照rtfMRI-nf干预的双盲条件 接受过调节顶叶区域的训练，推测该区域与情绪处理或MDD无关。成功将会 建议对传统耐药人群进行新的非药物、非侵入性干预 MDD患者的比例。

Abstract Up to two-thirds of patients diagnosed with major depressive disorder (MDD) will not respond to standard pharmacological and psychological interventions and will be considered treatment resistant (TR-MDD). Decreased reactivity to positive stimuli, indexed by low amygdala reactivity to positive autobiographical memory recall, may be a causal mechanism interfering with recovery from TR-MDD. Previous work in our lab suggests that individuals who do respond to antidepressant medications show increased amygdala activity that is indistinguishable from controls relative to baseline, while TR-MDD individuals fail to show this increase in amygdala activity. Furthermore, we have found that MDD participants (more generally, not specifically TR- MDD) are indeed 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 whether rtfMRI-nf training to increase the amygdala response to positive memories may serve as an intervention for TR-MDD. The R61 period will involve intervention refinement and evaluation of mechanism; N=40 TR-MDD individuals will undergo five amygdala rtfMRI-nf training sessions and we will assess changes in amygdala activity with the goal of confirming that patients with TR-MDD are able to increase the amygdala response to positive memories, and to determine the minimal number of training sessions required for sufficient target engagement/amygdala asymptote to be reached. The R33 phase will involve a mechanistic comparison to a control intervention and evaluation of clinical change (including duration of effects). N=60 TR-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 are trained to regulate a parietal region putatively not involved in emotional processing or MDD. Success will suggest a new non-pharmacological, non-invasive intervention for a traditionally treatment-resistant population of MDD individuals.