Department of Anesthesia, Pain Management & Perioperative Medicine, Dalhousie University, NSHA, Halifax B3H 1V7, Canada.
Harvard Medical School, Mass General Hospital, Boston, MA. 02129, USA.
Neuroimage. 2022 Sep;258:119349. doi: 10.1016/j.neuroimage.2022.119349. Epub 2022 Jun 8.
Top-down processes such as expectations play a key role in pain perception. In specific contexts, inferred threat of impending pain can affect perceived pain more than the noxious intensity. This biasing effect of top-down threats can affect some individuals more strongly than others due to differences in fear of pain. The specific characteristics of intrinsic brain characteristics that mediate the effects of top-down threat bias are mainly unknown. In this study, we examined whether threat bias is associated with structural and functional brain connectivity. The variability in the top-down bias was mapped to the microstructure of white matter in diffusion weighted images (DWI) using MRTrix3. Mean functional connectivity of five canonical resting state networks was tested for association with bias scores and with the identified DWI metrics. We found that the fiber density of the splenium of the corpus callosum was significantly low in individuals with high top-down threat bias (FWE corrected with 5000 permutations, p < 0.05). The mean functional connectivity within the language/memory and between language/memory and default mode networks predicted the bias scores. Functional connectivity within language memory networks predicted the splenium fiber density, higher pain catastrophizing and lower mindful awareness. Probabilistic tractography showed that the identified region in the splenium connected several sensory regions and high-order parietal regions between the two hemispheres, indicating the splenium's role in sensory integration. These findings demonstrate that individuals who show more change in pain with changes in the threat of receiving a stronger noxious stimulus have lower structural connectivity in the pathway necessary for integrating top-down cue information with bottom-up sensory information. Conversely, systems involved in memory recall, semantic and self-referential processing are more strongly connected in people with top-down threat bias.
自上而下的过程，如预期，在疼痛感知中起着关键作用。在特定的情况下，对即将到来的疼痛的推断威胁可以比伤害的强烈程度更能影响感知的疼痛。这种自上而下的威胁的偏向效应可能会由于对疼痛的恐惧的差异而对某些个体的影响更大。介导自上而下的威胁偏见影响的内在大脑特征的具体特征主要是未知的。在这项研究中，我们检查了威胁偏见是否与结构和功能大脑连接有关。使用 MRTrix3，通过扩散加权图像（DWI）将自上而下的威胁偏差的可变性映射到白质的微观结构上。对五个典型的静息状态网络的平均功能连接进行了测试，以与偏差得分和识别的 DWI 指标相关联。我们发现，在具有高自上而下的威胁偏见的个体中，胼胝体压部的纤维密度明显较低（经 5000 次置换的 FWE 校正，p < 0.05）。语言/记忆和语言/记忆与默认模式网络之间的平均功能连接预测了偏差分数。语言记忆网络内的功能连接预测了胼胝体纤维密度，更高的疼痛灾难化和更低的正念意识。概率性轨迹追踪显示，胼胝体中的确定区域连接了两个半球之间的几个感觉区域和高级顶叶区域，表明胼胝体在感觉整合中的作用。这些发现表明，在接受更强的伤害性刺激的威胁时，疼痛变化更大的个体在整合自上而下的线索信息与自下而上的感觉信息所需的通路中具有较低的结构连接。相反，在具有自上而下的威胁偏见的人中，涉及记忆回忆、语义和自我参照处理的系统的连接更强。
