Neurofeedback and Neural Plasticity of Self-Processing and Affect Regulation Circuits in Suicide Attempting Adolescents

项目摘要 响应RFA-MH-18-704的这一分阶段创新申请寻求初始（R61）2年的支持 阶段的里程碑驱动测试的神经目标的干预，通过一种新的神经反馈（NF）治疗。 使用NF，我们将针对青少年（13-17岁）的情感调节和自我处理的神经回路 有明显的自杀意念和最近的自杀企图实现我们提出的里程碑 将触发额外三年的支持（R33阶段），以确认更大样本中的目标参与 随机分配至活性NF干预组与安慰剂NF组，以评估靶点之间的关系 职能成果的参与和变化。情感失调和异常自我加工预测 在高危人群中反复尝试自杀。药物或行为无法充分解决这些问题 治疗。NF培训在先前安慰剂对照NF中在这些维度上实现了持久改善 审判为了进一步发展这种干预，我们试图首先确定NF最佳参与的神经靶点， 情绪调节和自我处理的关键时期。我们的试验数据和理论考虑支持 杏仁核或dACC活性增加及其功能连接（FC） 与中前额叶皮层（mPFC）代表通过NF训练可治疗的目标。在R61初始阶段 我们将估计dACC和杏仁核活动及其FC的干预相关增加的效应大小， 在自我处理和情感调节任务中，每个位点20名青年使用mPFC进行高质量成像， 临床数据。这一阶段的目标是确定哪些基因座在青少年中上调最好， 与功能目标的改善有关。如果我们达到了我们提出的增加dACC的里程碑， 杏仁核活动及其与mPFC的FC超过了特定的效应大小，并解释了一个明显的 在情感调节和自我处理行为的方差的比例，我们将继续R33 相位在R33阶段，我们将扩大研究，测试70名随机接受积极NF干预的青少年 (dACC或杏仁核）或安慰剂NF。对于这两个阶段，我们将获得最先进的磁共振 主要关注功能性MRI的MRI数据。我们在R33阶段的具体目标是确认 随机分配至活性药物组与安慰剂NF组的目标参与度;检查 神经靶点的变化与情感调节、自我处理和 自杀意念;并确定改善功能结果的介质。支持有效性的证据 dACC或杏仁核回路作为可修改的神经靶点将支持未来的研究， 增强青少年神经反馈的有效性。重要的是，即使是负面的结果也会 关于神经反馈的位置和方向的信息（顶部=dACC与下=杏仁核）， 取得了实质性的效果。脑成像的不确定结果仍将为未来的贝叶斯先验提供信息 研究情绪调节和自我加工障碍的神经基质及其改善。

PROJECT SUMMARY This phased innovation application in response to RFA-MH-18-704 seeks support for an initial (R61) 2-year phase for milestone-driven testing of neural targets of intervention by a novel neurofeedback (NF) treatment. Using NF, we will target the neurocircuitry of affect regulation and self-processing in adolescents (ages 13-17) who have current significant suicide ideation and a recent suicide attempt. Attaining our proposed milestones would trigger support for three additional years (R33 phase) to confirm target engagement in a larger sample with random assignment to active NF intervention vs. Placebo NF, to assess the relationships between target engagement and changes in functional outcomes. Affect dysregulation and abnormal self-processing predict repeated suicide attempts in at risk populations. They are insufficiently addressed by medications or behavioral treatments. NF training elicits enduring improvements in those dimensions in prior Placebo controlled NF trials. To further develop this intervention, we seek to first identify the neural target best engaged by NF during a critical period for affect regulation and self-processing. Our pilot data and theoretical considerations support the overarching hypothesis that increased amygdala or dACC activity and their functional connectivity (FC) with the middle prefrontal cortex (mPFC) represent treatable targets via NF training. In the initial R61 phase we will estimate the effect size of intervention-related increases in dACC and amygdala activity and their FC with mPFC during self-processing and affect regulation task in 20 youth per loci with high-quality imaging and clinical data. The goal of this phase is to determine which loci is best up-regulated in adolescents and is associated with functional targets improvements. If we meet our proposed milestone that increased dACC or amygdala activity and their FC with the mPFC exceed a specific effect size and account for an appreciable proportion of the variance in affect regulation and self-processing behavior, we would proceed to the R33 phase. In the R33 phase, we will expand the study to test 70 adolescents randomized to active NF intervention (dACC or Amygdala) or to a placebo NF. For both phases, we will obtain state-of-the-art magnetic resonance imaging (MRI) data with a primary focus on functional MRI. Our specific aims in the R33 phase are to confirm target engagement in the groups randomized to active vs. the Placebo NF group; to examine the relationship between changes in the neural target and clinical improvements in affect regulation, self-processing and suicide ideation; and to identify mediators of improved functional outcomes. Evidence supporting the validity of dACC or amygdala circuits as a modifiable neural target would then support future studies to further enhance the effectiveness of neurofeedback in adolescents. Importantly, even negative results will be informative regarding the location and direction of neurofeedback (top=dACC vs. down=amygdala) that best attains substantial effects. Inconclusive results from brain imaging would still inform Bayesian priors for future studies of the neural substrates of affect regulation and self-processing impairments and their amelioration.