Timmers Inge, López-Solà Marina, Heathcote Lauren C, Heirich Marissa, Rush Gillian Q, Shear Deborah, Borsook David, Simons Laura E
Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University School of Medicine, Palo Alto, CA, United States.
Serra Hunter Program, Unit of Psychological Medicine, Department of Medicine, School of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
Pain. 2022 Apr 1;163(4):719-728. doi: 10.1097/j.pain.0000000000002410.
There is a need to identify brain connectivity alterations predictive of transdiagnostic processes that may confer vulnerability for affective symptomology. Here, we tested whether amygdala resting-state functional connectivity (rsFC) mediated the relationship between catastrophizing (negative threat appraisals and predicting poorer functioning) and altered threat-safety discrimination learning (critical to flexibly adapt to new and changing environments) in adolescents with persistent pain. We examined amygdala rsFC in 46 youth with chronic pain and 29 healthy peers (age M = 15.8, SD = 2.9; 64 females) and its relationship with catastrophizing and threat-safety learning. We used a developmentally appropriate threat-safety learning paradigm and performed amygdala seed-based rsFC and whole-brain mediation analyses. Patients exhibited enhanced connectivity between the left amygdala and right supramarginal gyrus (SMG) (cluster-level P-FDR < 0.05), whereas right amygdala rsFC showed no group differences. Only in patients, elevated catastrophizing was associated with facilitated threat-safety learning (CS+>CS-; rp = 0.49, P = 0.001). Furthermore, in patients, elevated catastrophizing was associated with reduced left amygdala connectivity with SMG / parietal operculum, and increased left amygdala connectivity with hippocampus, dorsal striatum, paracingulate, and motor regions (P < 0.001). In addition, blunted left amygdala rsFC with right SMG/parietal operculum mediated the association between catastrophizing and threat-safety learning (P < 0.001). To conclude, rsFC between the left amygdala (a core emotion hub) and inferior parietal lobe (involved in appraisal and integration of bodily signals and attentional reorienting) explains associations between daily-life relevant catastrophizing and threat-safety learning. Findings provide a putative model for understanding pathophysiology involved in core psychological processes that cut across diagnoses, including disabling pain, and are relevant for their etiology.
有必要识别出可预测跨诊断过程的大脑连接改变，这些过程可能会导致情感症状的易感性。在此，我们测试了杏仁核静息态功能连接（rsFC）是否介导了灾难化思维（负面威胁评估并预示功能较差）与持续性疼痛青少年中改变的威胁-安全辨别学习（对灵活适应新的和不断变化的环境至关重要）之间的关系。我们检查了46名患有慢性疼痛的青少年和29名健康同龄人（年龄M = 15.8，标准差 = 2.9；64名女性）的杏仁核rsFC及其与灾难化思维和威胁-安全学习的关系。我们使用了适合发育阶段的威胁-安全学习范式，并进行了基于杏仁核种子的rsFC和全脑中介分析。患者左侧杏仁核与右侧缘上回（SMG）之间的连接增强（聚类水平P-FDR < 0.05），而右侧杏仁核rsFC未显示出组间差异。仅在患者中，灾难化思维程度升高与促进威胁-安全学习相关（CS+>CS-；rp = 0.49，P = 0.001）。此外，在患者中，灾难化思维程度升高与左侧杏仁核与SMG/顶叶岛盖的连接减少以及左侧杏仁核与海马体、背侧纹状体、扣带旁回和运动区域的连接增加相关（P < 0.001）。此外，左侧杏仁核与右侧SMG/顶叶岛盖的rsFC减弱介导了灾难化思维与威胁-安全学习之间的关联（P < 0.001）。总之，左侧杏仁核（一个核心情绪枢纽）与顶下叶（参与身体信号的评估和整合以及注意力重新定向）之间的rsFC解释了与日常生活相关的灾难化思维和威胁-安全学习之间的关联。研究结果为理解涉及跨诊断的核心心理过程（包括致残性疼痛）及其病因的病理生理学提供了一个假定模型。
