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

项目总结 响应RFA-MH-18-704的这一阶段性创新应用寻求对初始(R61)2年期的支持 通过一种新的神经反馈(NF)治疗对干预的神经目标进行里程碑驱动测试的阶段。 使用神经营养因子，我们将针对青少年(13-17岁)的情绪调节和自我处理的神经回路 他们目前有严重的自杀意念和最近一次自杀未遂。达到我们建议的里程碑 将触发额外三年(R33阶段)的支持，以确认更大样本中的目标参与度 通过随机分配到积极的神经营养因子干预和安慰剂神经营养因子，以评估靶点之间的关系 参与和功能结果的变化。情绪调节失调与异常自我加工预测 在高危人群中反复尝试自杀。药物或行为疗法不足以解决这些问题 治疗。与之前的安慰剂对照的神经营养因子相比，神经营养因子训练在这些维度上产生了持久的改善 审判。为了进一步发展这种干预，我们寻求首先确定神经营养因子在治疗期间最佳的神经靶点 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性(FC)的总体假设 与中前额叶皮质(MPFC)一起，代表了通过神经营养训练的可治疗靶点。在初始R61阶段 我们将估计与干预相关的dACC和杏仁核活动增加的影响大小及其FC 在自我处理过程中使用mPFC，并影响每个座位20名年轻人的调节任务，具有高质量的成像和 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，并且 与功能目标改进相关。如果我们达到我们提议的里程碑，即增加dACC或 杏仁核活动及其与mPFC的FC超过特定的效应大小，并占可察觉的 影响调节和自我加工行为的差异比例，我们将继续进行R33 相位。在R33阶段，我们将扩大研究范围，测试70名随机接受主动神经营养因子干预的青少年 (dACC或杏仁核)或给安慰剂核因子。对于这两个阶段，我们都将获得最先进的磁共振 成像(MRI)数据，主要侧重于功能MRI。我们在R33阶段的具体目标是确认 随机分为积极组和安慰剂组的目标参与度；以检查两者之间的关系 在神经靶点的变化和临床上情感调节、自我处理和治疗的改善之间 自杀意念；并确定改善功能结果的中介因素。支持有效性的证据 将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，以进一步 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将是 关于神经反馈的位置和方向(顶部=dACC与向下=杏仁核)的信息最好 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 情绪调节和自我处理障碍的神经基础及其改善的研究。

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.