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

在美国，偏头痛影响着600多万儿童和青少年，并导致严重的疼痛和残疾。 认知行为疗法(CBT)有效地减少了儿童患者的头痛天数。 CBT包括不同的组成部分，包括精神和身体途径(深呼吸、进行性肌肉 放松、想象、生物反馈)和认知再评价训练(CR)。而中国的新战略计划 国家补充和综合健康中心强调“神经生物学效应和 作为非药物性疼痛研究的重中之重的大脑机制， CBT工作的组成部分仍然没有得到很好的描述。为了剖析CBT所涉及的神经机制，我们 将进行一项机械性临床试验，以比较80名患有偏头痛的年轻人(年龄在10岁至17岁之间) 接受放松训练(BART)至80名接受CR训练的人。功能磁共振成像与定量感觉 将在干预前后(为期8周)获得测试(QST)数据，以实现这些目标：AIM 1A.BART和CR训练是否会以与头痛相关的方式不同地改变静息大脑的激活 减价？我们的初步数据表明，偏头痛患者有促进伤害性连接的功能模式 而CBT则产生杏仁核功能连接的抗伤害性模式。我们 假设BART在CR训练时优先激活腹内侧前额叶皮质(VmPFC) 将优先激活背外侧前额叶皮质(DlPFC)和其他认知控制区域。至 为了测试这一点，动脉自旋标记(ASL)核磁共振将被用来比较稳定训练前后的差异。 BART组和CR组处于脑激活状态。静息状态BOLD fMRI将用于确定BART和 CR训练导致vmPFC和dlPFC与 杏仁核。目标1B。BART和CR的主动行为是否以不同的方式招募vmPFC和 DLPFC？来自CBT的初步数据是在休息期间获得的，可能反映了运动的积极影响 治疗/减轻头痛，而不是在积极参与期间涉及的阶段性机制 BART/CR策略。为了进一步确定BART和CR是否涉及不同的大脑机制，ASL和CR BOLD MRI将用于比较活动期间大脑的激活和杏仁核功能的连通性 每种治疗的表现与休息。目的2.痛觉调制的效率能预测头痛吗 BART与CR相比减少了多少？条件性疼痛调制(CPM)疗效的QST评估 提供了内源性疼痛调节机制在疼痛条件和疼痛条件下参与的索引 疼痛治疗。我们的初步工作表明，CPM的低效率预示着头痛。 CBT后减少。然而，BART与CR相比，在存在 扰乱了内源性疼痛的调制。因此，前处理的CPM将被用来检验低 CPM的有效性将不同地预测BART和CR后头痛的缓解。

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.