Identifying pain-specific connectivity in the human brain

我们都经历过痛苦。它是潜在伤害的信号，包括感官、情感、动机和认知维度，必须将这些维度整合起来，才能做出适当的反应。使用功能性磁共振成像（fMRI）进行的脑成像研究一再表明，对个体进行疼痛刺激会导致大脑活动的一致模式。然而，这种模式并不是疼痛特有的——事实上，这种模式与触摸刺激无法区分。这是因为观察到的模式代表了疼痛吸引我们注意力的程度——也就是说，疼痛的显著性。因此，还没有一个特定于疼痛的大脑区域，或一组大脑区域。虽然疼痛和触觉之间的激活模式无法区分，但这些刺激感觉非常不同，因此在大脑中必须有不同的表征。******大脑各区域并不是孤立地起作用的。它们形成网络来整合信息并产生感知体验和行为。因此，尽管相同的大脑区域被触觉和疼痛激活，但这些区域可能与不同的区域形成网络。确定这种情况是否属实，可以揭示大脑感知疼痛的基本机制。******这个建议的总体目标是确定疼痛感知的机制。为了实现这一点，我们将识别疼痛刺激和触摸刺激时的网络差异，这些差异已经被匹配为显著性。然而，考虑到疼痛和触觉在感知上是不同的——疼痛本质上是不愉快的，而触觉不是——确定触觉和疼痛之间的大脑差异是否与不愉快有关，而不是与疼痛本身有关，这一点很重要。回答这个问题的一种方法是比较不同方式的不愉快刺激所引起的大脑活动。因此，本研究的第二个目的是比较已识别的疼痛连接是否通过三种不同的方式（视觉、触觉和伤害感受）编码不愉快的刺激。第三，疼痛特异性连通性的强度可能与感知到的疼痛强度有关。本研究的第三个目的是测试疼痛特异性连接是否表现出对不同刺激强度的分级反应。最后，我们将利用新的结构脑成像技术确定是否存在观察到的疼痛特异性连接的结构基础。这些研究将极大地促进我们对疼痛系统的基本理解，并对健康研究人员开发疼痛生物标志物和识别新的治疗标志物具有深远的转化影响。

We have all experienced pain. It signals potential injury, and comprises sensory, emotional, motivational and cognitive dimensions, which must be integrated to mount an appropriate response. Brain imaging studies using functional magnetic resonance imaging (fMRI) have repeatedly shown that subjecting individuals to painful stimuli results in a consistent pattern of brain activity. However, this pattern is not pain specific — in fact, this pattern is indistinguishable from a touch stimulus. This is because the observed pattern represents the extent to which pain captures our attention — i.e., pain's salience. As such, there has yet to be a pain-specific brain region, or set of brain regions. Although the activation pattern is indistinguishable between pain and touch, these stimuli feel very different, and thus must have different representations in the brain.******Brain regions do not function in isolation. They form networks to integrate information and produce perceptual experiences and behaviour. Therefore, although the same sets of brain regions are activated by touch and pain, these regions may be forming networks with different regions. Determining if this is the case could reveal a fundamental mechanism by which pain is perceived in the brain. ******The overall aim of this proposal is to identify a mechanism for pain perception. To achieve this, we will identify network differences during painful and touch stimuli, that have been matched for salience. However, given that pain and touch are perceptually different — pain is inherently unpleasant, whereas touch is not — it is important to determine whether brain differences between touch and pain are related to unpleasantness, rather than pain itself. One way to answer this question is to compare brain activity elicited by unpleasant stimuli from different modalities. Therefore, the second aim of this study is to compare whether the identified pain connectivity 1 encodes unpleasant stimuli across three different modalities: visual, tactile and nociceptive. Third, the strength of pain-specific connectivity may be related to the intensity of the pain perceived. The third aim of this study is to test whether the pain specific connectivity shows a graded response to different stimulus intensities. Finally, we will determine whether there is a structural basis for the observed pain-specific connectivity using novel structural brain imaging techniques. These studies will greatly advance our fundamental understanding of the pain system, and have profound translational impact for health researchers to develop a biomarker for pain, and identify novel therapeutic markers.