fMRI Resting State Networks in Chronic Pain

描述(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，可能会导致抑郁、失眠、免疫功能低下、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知，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动荡状况对大脑健康造成的负担的性质和长期后果。最近在健康受试者身上的fMRI结果极大地促进了这一目标的实现，这些结果识别了在空闲或被动的心理过程中活跃的皮质区域的子集，这些脑区参与了所谓的“休息状态网络”(RSN)。目的：确定慢性下腰痛患者与健康受试者的RSNs组成脑区。目的II将确定患者和正常受试者每个RSN组件之间的功能相互作用，以更好地了解在慢性疼痛中工作的基本皮质机制。最后，AIM III将确定这些静止的国家网络在健康和疾病方面的组织中的性别差异和激素依赖。FMRI数据将从健康受试者和疼痛患者中收集，并使用概率独立分量分析等多变量技术进行分析，正如我们的初步结果所示，这能够明确地识别RSN中涉及的主要分量。每种静息状态和慢性疼痛网络的组成的验证将通过假设驱动的通用线性模型双变量分析进行，该分析基于目前对皮质参与慢性疼痛的理解。由于识别慢性疼痛患者静息状态网络的时空成分相当于准确地了解疼痛在大脑中的位置，因此它的成功发现将极大地改变我们对导致慢性疼痛的大脑区域的理解。这一知识应该会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。与公共卫生相关有积累的证据表明，慢性疼痛如果不治疗，可能会导致抑郁、失眠、免疫功能低下、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知，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。该项目将分离为慢性疼痛患者(如我们)的休息状态服务的大脑网络的组件，以确定这种不稳定状况对大脑长期健康造成的负担的影响。这种关于“疼痛在大脑中的位置”的精确知识，将极大地改变我们对导致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.