Amygdala rtfMRI Neurofeedback for Treatment Resistant Depression

摘要 多达三分之二的诊断为重度抑郁症（MDD）的患者对标准治疗没有反应。 药物和心理干预，并将被视为治疗抵抗（TR-MDD）。 对积极刺激的反应性降低，以杏仁核对积极自传体的低反应性为指标 记忆回忆，可能是干扰TR-MDD恢复的因果机制。我们实验室以前的工作 研究表明，对抗抑郁药物有反应的个体表现出杏仁核活动的增加， 相对于基线，与对照组没有区别，而TR-MDD个体未能表现出这种增加 杏仁核活动此外，我们发现MDD参与者（更一般地说，不具体地说，TR- 通过实时功能磁共振成像， 神经反馈（rtfMRI-nf）训练，这种增加与大而快速的减少有关， 抑郁症状在这里，我们建议评估rtfMRI-NF训练是否增加杏仁核 对积极记忆的反应可以作为TR-MDD的干预。R61期间将涉及 干预细化和机制评估; N = 40名TR-MDD个体将接受5个杏仁核 rtfMRI-nf训练课程，我们将评估杏仁核活动的变化，目的是确认 TR-MDD患者能够增加杏仁核对积极记忆的反应，并确定 足够的目标参与/杏仁核渐近线所需的最小训练次数 达到了R33阶段将涉及与对照干预的机械比较和评估 临床变化（包括影响持续时间）。N = 60名TR-MDD受试者将随机分配至 杏仁核rtfMRI-nf干预或对照rtfMRI-nf干预的双盲条件， 被训练来调节不参与情绪处理或MDD的顶叶区域。成功将 这为传统治疗抵抗人群提供了一种新的非药物性、非侵入性干预措施 MDD患者。

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.