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

描述（由申请人提供）：身心治疗，如冥想，瑜伽或催眠，已被证明可以改善几种持续性疼痛疾病的主观症状，包括肠易激综合征（IBS）。然而，能够帮助识别治疗反应的客观、可靠的测量方法（“生物标志物”）尚未开发出来。生物标志物可以支持临床终点，并用于更全面地评估身心临床试验的机制和结果，以及比较各种补充和综合医学治疗，并有助于针对最有可能受益的患者进行特定治疗。最近发现的IBS和其他慢性疼痛疾病患者的功能和结构脑成像异常是有吸引力的生物标志物候选者，但尚未得到验证。例如，我们的研究小组已经发现，在IBS中，休息时自发脑振荡的时空模式、疼痛预期期间脑区域之间的功能连接以及前额叶脑区结构密度的变化都发生了变化。临床症状的严重程度与某些大脑异常也有相关性。基于这些初步发现，我们提出了一个循序渐进的过程，遵循既定的生物标志物验证指南，以确定以下内容：目的1：开发和验证大脑结构和功能改变作为IBS中CAM相关治疗变化的候选生物标志物。每个提出的生物标志物将通过其区分患者和健康对照（HC）的能力、与主观症状严重程度的相关性以及随时间的稳定性来验证。我们提出的候选生物标志物包括：静息状态下右前脑岛对低频功率的贡献增加，疼痛预期时杏仁核的连通性改变，前额叶皮层灰质减少的结构标记。目标2：通过评估IBS患者在正念减压（MBSR）后对治疗反应性的关系，验证目标1中最佳的生物标志物候选物。目标3：通过检查性别、年龄、共病疼痛症状和/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中最佳生物标志物的普遍性，这些因素是生物标志物效用与初始和三个月预后相关的调节因素。这些目标将通过两项研究来实现。第一组将在单次影像学检查中检查75名肠易激综合征患者和30名健康对照者，其中30名肠易激综合征患者在2-4周后返回第二次影像学检查，以检验目的1的假设。第二项研究将对50名IBS患者在MBSR项目前后进行影像学和症状问卷调查，以检验目标2和目标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.