Brain network correlates of tonic and chronic pain

疼痛是一种复杂的、高度主观的体验，它具有重要的保护功能。然而，在慢性疼痛状态下，持续疼痛不再具有保护功能，而是一种对生活质量具有破坏性影响的病理状态。最近的证据表明，大脑积极参与慢性疼痛的发展和维持。然而，慢性疼痛的大脑机制尚不完全清楚。因此，在前面的项目中，我们已经开始使用脑电描记(EEG)来研究长期实验性和临床疼痛的大脑相关性。拟议的项目更新建立在前一个项目的范例和分析的基础上，并将我们的方法从评估与疼痛相关的大脑活动扩展到全面调查大脑连通性，即人类大脑中的沟通如何与持续的疼痛相关。在100名慢性背痛患者和100名健康受试者中，我们将使用最新的大脑连通性测量来评估神经元通信，这些测量克服了传统脑电分析的场扩散和体积传导限制。基于这些连通性测量，我们将对持续的紧张性和慢性疼痛期间的大脑连通性进行及时的基于图论的网络分析。彻底的临床和心理评估将允许将大脑连接的网络测量与个人的临床和心理特征联系起来。基于我们之前的发现，我们假设目前正在进行的实验和临床疼痛的强度是由内侧前额叶皮质的局部伽马振荡反映的，这是以β和/或theta频率连接的大脑网络中的一个重要节点。我们进一步假设，慢性疼痛与大脑连接的额外全球变化有关，例如，小世界的减少。我们预计，这些全球网络的变化反映了长期的疼痛相关残疾，而不是目前的疼痛强度，因此在健康对照组中没有观察到。在下一步，我们将使用多变量模式分析来测试大脑连接的模式是否可以用来解码持续的疼痛。这一方法有助于建立慢性疼痛的神经元标志物，为慢性疼痛的诊断和分类以及疼痛治疗的监测和优化提供支持。因此，拟议的项目更新有望对疼痛的大脑机制提供新的见解，并可能对慢性疼痛的诊断和治疗产生影响。

Pain is a complex and highly subjective experience, which subserves vital protective functions. However, in chronic pain states, ongoing pain no longer subserves protective functions but represents a pathological condition with devastating effects on quality of life. Recent evidence indicates that the brain is actively involved in the development and maintenance of chronic pain. However, the cerebral mechanisms of chronic pain are not fully understood. In the preceding project, we have therefore started to investigate the cerebral correlates of long-lasting experimental and clinical pain using electroencepahlography (EEG). The proposed project renewal builds upon the paradigms and analyses of the previous project and extends our approach from the assessment of pain-related brain activity to the comprehensive investigation of brain connectivity, i.e., how communication in the human brain relates to ongoing pain. In 100 patients suffering from chronic back pain and 100 healthy human subjects, we will assess neuronal communication using recent brain connectivity measures, which overcome field spread and volume conduction limitations of traditional EEG analyses. Based on these connectivity measures we will perform timely graph theory-based network analyses of brain connectivity during ongoing tonic and chronic pain. A thorough clinical and psychological assessment will allow for relating network measures of brain connectivity to the individual clinical and psychological characteristics. Based on our previous findings, we hypothesize that the current intensity of ongoing experimental and clinical pain is reflected by local gamma oscillations in medial prefrontal cortex, which represents an important node in a brain network connecting at beta and/or theta frequencies. We further hypothesize that chronic pain is associated with additional global changes of brain connectivity, e.g., a reduction in small-worldness. We expect that these global network changes reflect long-term pain-related disability rather than the current pain intensity and are therefore not observed in healthy controls. In a further step, we will use multivariate pattern analysis to test whether patterns of brain connectivity can be used to decode ongoing pain. This approach could help to establish neuronal markers of chronic pain, which might support the diagnosis and classification of chronic pain and the monitoring and optimization of pain therapy. The proposed project renewal, thus, promises novel insights into the brain mechanisms of pain with possible implications for the diagnosis and treatment of chronic pain.