Dissecting Neural Mechanisms Supporting Mind and Body Approaches to Pain Reduction in Youth with Migraine

偏头痛影响美国超过600万儿童和青少年，并导致严重的疼痛和残疾。 认知行为疗法（CBT）有效地减少了儿科患者的头痛天数。 CBT包括不同的组成部分，包括心灵和身体方法（深呼吸，渐进肌肉 放松、想象、生物反馈）和认知再评价训练（CR）。虽然新的战略计划， 国家补充和综合健康中心强调“神经生物学效应和 机制”作为非药物疼痛研究的首要科学优先事项， CBT工作的组成部分仍然没有得到很好的界定。为了剖析CBT的神经机制，我们 将进行一项机械临床试验，比较80名青少年（10至17岁）的偏头痛样本， 接受放松训练（BART）的80人接受CR训练。功能磁共振成像和定量感觉 将在干预前后（8周）获得测试（QST）数据，以解决这些目标： 1A. BART和CR训练是否以与头痛相关的方式不同地改变静息脑激活 减少？我们的初步数据表明，偏头痛患者具有功能连接的亲伤害性模式 而CBT产生杏仁核功能连接的抗伤害性模式。我们 假设BART将优先激活腹内侧前额叶皮层（vmPFC），而CR训练 将优先激活背外侧前额叶皮层（dlPFC）和其他认知控制区域。到 为了验证这一点，动脉自旋标记（ASL）MRI将用于比较稳定的训练前后差异。 说明BART和CR组的脑激活。静息状态BOLD fMRI将用于确定BART和 CR训练对vmPFC和dlPFC的功能连接产生不同的改变， 杏仁核目标1B。BART和CR的主动性能是否差异性地募集vmPFC的激活， dlPFC？CBT的初步数据是在休息时获得的，可能反映了 治疗/头痛减少，而不是在积极参与的阶段性机制， BART/CR战略。为了进一步确定BART和CR是否涉及不同的脑机制，ASL和 BOLD MRI将用于比较活动期间的大脑激活和杏仁核功能连接。 每次治疗与休息的性能。目标2.疼痛调节的效率能预测头痛吗 BART与CR后的减少？QST评估条件性疼痛调制（CPM）的效率 提供了疼痛状况中内源性疼痛调节机制的参与指数， 疼痛治疗我们的初步工作表明，CPM的低效率是头痛的预测 减少CBT。然而，目前尚不清楚BART与CR在存在以下情况下是否更有效： 破坏了内源性疼痛调节因此，治疗前CPM将用于检验低 CPM的有效性将是BART与CR后头痛减少的差异预测。

Migraine affects over 6 million children and adolescents in the U.S. and leads to significant pain and disability. Cognitive behavioral therapy (CBT) effectively reduces the number of headache days in pediatric patients. CBT includes distinct components, including mind and body approaches (deep breathing, progressive muscle relaxation, imagery, biofeedback) and cognitive reappraisal training (CR). While the new strategic plan of the National Center for Complementary and Integrated Health highlights “Neurobiological Effects and Mechanisms” as a top scientific priority for non-pharmacological pain research, the brain mechanisms by which components of CBT work remain poorly delineated. To dissect the neural mechanisms engaged by CBT, we will conduct a mechanistic clinical trial to compare a sample of 80 youth (ages 10 to 17) with migraine who receive relaxation training (BART) to 80 who receive CR training. Functional MRI and quantitative sensory testing (QST) data will be obtained before and after intervention (an 8 week period) to address these aims: Aim 1A. Do BART and CR training differentially alter resting brain activation in a fashion related to headache reduction? Our pilot data indicate migraine patients have pro-nociceptive patterns of functional connectivity with the amygdala while CBT produces anti-nociceptive patterns of amygdalar functional connectivity. We hypothesize that BART will preferentially activate the ventromedial prefrontal cortex (vmPFC) while CR training will preferentially activate the dorsolateral prefrontal cortex (dlPFC) and other regions of cognitive control. To test this, arterial spin labeling (ASL) MRI will be used to compare pre vs. post training differences in steady state brain activation in BART and CR groups. Resting state BOLD fMRI will be used to determine if BART and CR training produce differential alterations of the functional connectivity of the vmPFC and dlPFC with the amygdala. Aim 1B. Does active performance of BART and CR differentially recruit activation of the vmPFC and dlPFC? Preliminary data from CBT were obtained during rest and may reflect tonically active consequences of therapy/headache reduction rather than the phasic mechanisms involved during active engagement of BART/CR strategies. To further determine if BART and CR involve distinct brain mechanisms, both ASL and BOLD MRI will be used to compare brain activation and amygdalar functional connectivity during active performance of each treatment vs. rest. Aim 2. Does the efficiency of pain modulation predict headache reduction following BART vs. CR? QST assessment of the efficiency of conditioned pain modulation (CPM) provides an index of the involvement of endogenous pain modulatory mechanisms in both pain conditions and pain treatments. Our preliminary work has shown that low efficiency of CPM is predictive of headache reduction following CBT. However, it remains unknown if BART vs. CR is more effective in the presence of disrupted endogenous pain modulation. Thus, pre-treatment CPM will be used to test the hypothesis that low efficiency of CPM will be differentially predictive of headache reductions following BART vs. CR.