Abstract Background Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and bio-signatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related connectivity changes and their relationship to PTSD symptom improvements. Method Individuals (N=66) with a primary PTSD diagnosis participated in a randomized clinical trial of prolonged exposure therapy (N=36) vs. treatment waiting list (N=30). Task-free functional magnetic resonance imaging (fMRI) was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level-dependent (BOLD) responses were acquired. Intrinsic connectivity was assessed, by subregion, in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling (DCM) assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings. Results The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex, frontopolar, and sensory cortices; and decreased connectivity of both regions with left fronto-parietal nodes of the executive control network. Larger decreases in amygdala-frontal connectivity and insula-parietal connectivity were associated with larger PTSD symptom reductions. DCM evidence suggested treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions. Conclusions PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or bio-signature of recovery.

中文翻译：

---

创伤后应激障碍心理治疗后杏仁核和岛叶连接的变化：一项随机临床试验

摘要背景基于暴露的心理治疗是创伤后应激障碍（PTSD）的一线治疗，但其机制知之甚少。功能性大脑连接是识别治疗机制和治疗反应的生物特征的有前途的指标。为此，我们评估了杏仁核和岛叶治疗相关的连通性变化及其与 PTSD 症状改善的关系。方法 原发性 PTSD 诊断的个体 (N=66) 参加了延长暴露治疗 (N=36) 与治疗等待名单 (N=30) 的随机临床试验。无任务功能磁共振成像 (fMRI) 在随机化前和停止治疗/等待名单后 1 个月完成。获得了全脑血氧水平依赖性（BOLD）反应。在杏仁核和岛叶的亚区域评估了内在连接性，这是疾病病理生理学的关键边缘结构。动态因果建模 (DCM) 评估了通过内在连通性发现通知的选定节点中有效连通性变化的证据。结果 杏仁核和岛叶表现出广泛的主要亚区域一致的内在连通性变化模式，包括杏仁核和岛叶之间的连通性增加；两个区域与腹侧前额叶皮层、额极皮层和感觉皮层的连接性增加；并且两个区域与执行控制网络的左额顶叶节点的连接性降低。杏仁核-额叶连通性和岛叶-顶叶连通性的较大减少与较大的 PTSD 症状减少有关。DCM 证据表明，治疗减少了左杏仁核的左额抑制，而更大的减少与更大的症状减少有关。结论 PTSD 心理治疗适应性地减弱了休息时额顶叶和边缘脑回路之间的功能相互作用，这可能反映了恢复的潜在机制或生物特征。