fMRI Resting State Networks in Chronic Pain

描述（由申请人提供）：慢性疼痛仍然是人们寻求医疗保健的主要原因，如果不治疗，可能导致抑郁、失眠、免疫功能下降、饮食模式改变和其他长期有害影响。慢性疼痛患者有一种波动但持续的自发疼痛感，因此，与健康受试者相比，他们的大脑从未真正处于休息状态。该项目的总体目标是确定这种不稳定状况对大脑健康造成的负担的性质和长期后果。最近对健康受试者的功能磁共振成像（fMRI）结果极大地促进了这一目标，这些结果表明，在所谓的“静息状态网络”（Resting State Networks， RSN）中，在空闲或被动的心理过程中，皮层区域的子集是活跃的。目的一是鉴别慢性腰痛患者与健康受试者组成rsn的脑区。目的II将确定患者和正常受试者中每个RSN组成部分之间的功能相互作用，以更好地了解慢性疼痛的基本皮质机制。最后，第三目标将确定这些静息状态网络在健康和疾病组织中的性别差异和激素依赖性。FMRI数据将从健康受试者和疼痛患者中收集，并使用概率独立成分分析等多变量技术进行分析，如我们的初步结果所示，该技术能够明确识别涉及RSN的主要成分。每个静息状态和慢性疼痛网络的组成验证将通过假设驱动的一般线性模型双变量分析进行，该分析基于当前对慢性疼痛皮层参与的理解。由于对慢性疼痛患者静息状态网络的时空成分的识别相当于对“疼痛在大脑中的位置”的精确了解，它的成功发现将极大地改变我们对慢性疼痛大脑区域的理解。这一知识将影响到使用功能磁共振成像研究疼痛的实验方法，以及这种无效疾病的诊断和治疗结果。越来越多的证据表明，慢性疼痛如不治疗，可导致抑郁、失眠、免疫功能下降、饮食模式改变和其他长期有害影响。慢性疼痛患者有一种波动但持续的自发疼痛感，因此，与健康受试者相比，他们的大脑从未真正处于休息状态。该项目将分离慢性疼痛患者静息状态下大脑网络的组成部分，以确定这种不稳定状态对大脑长期健康的影响。这种“疼痛在大脑中的位置”的精确知识，将极大地改变我们对负责慢性疼痛的大脑区域的理解，影响使用功能磁共振成像研究疼痛的实验方法，以及这种无效疾病的诊断和治疗结果。

DESCRIPTION (provided by applicant): Chronic pain remains a primary reason for people seeking health care, which, if untreated, can lead to depression, insomnia, depressed immune function, changes in eating patterns, and other long-term deleterious effects. Chronic pain patients have a fluctuating but persistent spontaneous pain percept and therefore their brain, compared with healthy subjects, is never truly at rest. The overall objective of this project is to identify the nature and long-term consequences of the burden imposed by this unrest condition on the well being of the brain. This objective is greatly facilitated by recent fMRI results in healthy subjects which have identified the subset of cortical areas active during idle or passive mental processes engaged in the so called "Resting State Networks" (RSN). Aim I is to identify the brain regions comprising the RSNs in chronic low back pain patients as compared with those in healthy subjects. Aim II will determine the functional interactions between the components of each RSN in patients and normal subjects to better understand the basic cortical mechanisms at work in chronic pain. Finally Aim III will determine gender differences and hormonal dependence in the organization of these Resting State Networks, both in health and disease. FMRI data will be collected from healthy subjects and pain patients and analyzed with multivariate techniques such as Probabilistic Independent Component Analysis, which as shown in our preliminary results is able to unambiguously identify the major components involved in the RSN. The validation of the composition of each resting state and chronic pain networks will be conducted by hypothesis-driven General Linear Model bivariate analysis based on the current understanding of the cortical involvement in chronic pain. Since the identification of the spatio-temporal components of resting state network in chronic pain patients equals to a precise knowledge of "where the pain is in the brain", its successful uncovering will dramatically change our understanding of the brain areas responsible for chronic pain. This knowledge should impact both the experimental approach in the study of pain using fMRI, and the diagnosis and therapy outcome of this invalidating disease. PUBLIC HEALTH RELEVANCE There is accumulated evidence indicating that chronic pain if untreated, can lead to depression, insomnia, depressed immune function, changes in eating patterns, and other long- term deleterious effects. Chronic pain patients have a fluctuating but persistent spontaneous pain percept and therefore their brain, compared with healthy subjects, is never truly at rest. The project will isolate the components of the brain network subserving the resting state in chronic pain patients such us to identify the effect of the burden imposed by this unrest condition on the long term well being of the brain. This precise knowledge of "where the pain is in the brain", will dramatically change our understanding of the brain areas responsible for chronic pain, impacting both the experimental approaches in the study of pain using fMRI, and the diagnosis and therapy outcome of this invalidating disease.