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

描述（由申请人提供）：冥想、瑜伽或催眠等身心治疗已被证明可改善几种持续性疼痛疾病（包括肠易激综合征（IBS））的主观症状。然而，还没有开发出可以帮助识别治疗反应的客观、可靠的措施（“生物标志物”）。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中的机制和结果，以及比较各种补充和整合医学治疗，并帮助针对最有可能受益的患者进行特定治疗。最近确定的功能和结构的IBS和其他慢性疼痛疾病患者的脑成像异常是有吸引力的候选生物标志物，但尚未得到验证。例如，我们的研究小组在IBS中发现了休息时自发脑振荡的时空模式的改变、疼痛预期时脑区之间的功能连接的改变以及前额叶脑区结构密度的变化。临床症状严重程度与这些脑异常的相关性也已被证明。基于这些初步发现，我们提出了一个逐步的过程，以下生物标志物验证的既定指南，以确定以下内容：目的1：开发和验证脑结构和功能的变化作为候选生物标志物CAM相关的治疗变化在IBS。将通过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及其随时间推移的稳定性对每种拟定生物标志物进行验证。我们提出的候选生物标志物包括：在静息状态下增加右前额叶对低频功率的贡献，在疼痛预期期间改变杏仁核的连接，以及减少前额叶皮层灰质的结构标志物。目标二：通过评估IBS患者在基于正念减压（MBSR）后与治疗反应性的关系，从目标1中筛选最佳生物标志物候选物。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2中最佳生物标志物的一般性，作为生物标志物与初始和3个月结局相关的效用的调节因子。这些目标将通过两项研究来实现。第一个将在单次成像期间检查75名IBS患者和30名健康对照，其中30名IBS受试者在2-4周后返回进行第二次成像，以测试目标1的假设。第二项研究将在正念减压治疗前后对50名IBS患者进行影像学和症状问卷调查，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.