Neuroimaging biomarkers of Mind-Body treatment response in chronic visceral pain

描述(申请人提供)：心身疗法，如冥想、瑜伽或催眠，已被证明可以改善包括肠易激综合征(IBS)在内的几种持续性疼痛障碍的主观症状。然而，能够帮助确定治疗反应(“生物标记物”)的客观、可靠的措施尚未开发出来。生物标记物可以支持临床终点，并可用于在心身临床试验中更全面地评估机制和结果，以及比较各种补充和综合医学治疗方法，并帮助针对最有可能受益的患者进行特定治疗。最近发现的IBS和其他慢性疼痛障碍患者的功能和结构脑成像异常是有吸引力的候选生物标记物，但尚未得到验证。例如，我们的团队已经在IBS中发现了休息时自发脑振荡的时空模式的变化和疼痛预期时脑区域之间的功能连接的变化，以及前额叶脑区结构密度的变化。临床症状的严重程度与这些脑异常中的一些也显示出相关性。基于这些初步发现，我们建议一个循序渐进的过程，遵循已建立的生物标记物验证指南，以确定以下内容：目标1：开发和验证脑结构和功能改变作为肠易激综合征患者CAM相关治疗改变的候选生物标记物。每个建议的生物标记物将通过其区分患者和健康对照(HC)的能力、其与主观症状严重程度的相关性以及其随时间的稳定性来验证。我们提出的候选生物标记物包括：静息状态下右前岛对低频功率的贡献增加，预期疼痛期间杏仁核连接性改变，以及前额叶皮质灰质减少的结构标记物。目的2：通过评估IBS患者在基于正念的压力减轻(MBSR)后的治疗反应性，验证来自目标1的最佳生物标记物候选。目的3：通过检查性别、年龄、合并疼痛症状和/或基线疾病严重程度等因素之间的关系，确定目标1和目标2中最佳生物标记物的共性，作为生物标记物效用与初始和3个月结果相关的调节因素。这些目标将通过两项研究来实现。第一项研究将在一次成像会议期间检查75名IBS患者和30名健康对照，其中30名IBS患者在2-4周后重返第二次会议，以检验目标1的假设。第二项研究将在MBSR计划前后用成像和症状问卷对50名IBS患者进行测试，以检验目标2和3的假设。

DESCRIPTION (provided by applicant): Mind-Body treatments such as meditation, yoga or hypnosis have been shown to improve subjective symptoms in several persistent pain disorders including Irritable Bowel Syndrome (IBS). However, objective, reliable measures than can help identify treatment response ("biomarkers") have not been developed. A biomarker can support clinical endpoints and be used to more fully assess mechanisms and outcomes in Mind-Body clinical trials, as well as compare various Complementary and Integrative Medicine treatments, and help to target specific treatments to patients most likely to benefit. Recently identified functional and structural brain imaging abnormalities in patients with IBS and other chronic pain disorders are attractive biomarker candidates but have yet to be validated. For example, alterations in the spatiotemporal pattern of spontaneous brain oscillations during rest and in the functional connections between brain regions during pain expectation as well as changes in the structural density in prefrontal brain areas have been identified in IBS by our group. Correlations of clinical symptom severity with some of these brain abnormalities have also been shown. Based on these preliminary findings, we propose a step-wise process, following established guidelines for biomarker validation, to determine the following: Aim 1: Develop and validate structural and functional brain alterations as candidate biomarkers of CAM related treatment change in IBS. Each proposed biomarker will be validated by its ability to differentiate between patients and healthy controls (HC), its correlation with subjective symptom severity, and its stability over time. Our proposed candidate biomarkers include: increased right anterior insula contributions to low frequency power in the resting state, altered connectivity of the amygdala during anticipation of pain, and a structural marker of decreased prefrontal cortex gray matter. Aim 2: Validate optimal biomarker candidates from Aim 1 by assessment of their relationship to treatment responsiveness in IBS patients following Mindfulness Based Stress Reduction (MBSR). Aim 3: Determine the generality of optimal biomarkers from Aims 1 and 2 by examining relationship of factors such as sex, age, co-morbid pain symptoms, and/or baseline disease severity as moderators of the utility of the biomarker to be associated with initial and three month outcomes. These Aims will be accomplished in two studies. The first will examine 75 IBS patients and 30 healthy controls during a single imaging session with 30 of the IBS subjects returning for a second session 2-4 weeks later to test the hypotheses for Aim 1. The second study will test 50 IBS patients before and after the MBSR program with imaging and symptom questionnaires to test the hypotheses for Aims 2 and 3.