Heightened responding to uncertain threat is considered a hallmark of anxiety disorder pathology. We sought to determine whether individual differences in self-reported intolerance of uncertainty (IU), a key transdiagnostic dimension in anxiety-related pathology, underlies differential recruitment of neural circuitry during cue-signalled uncertainty of threat (n = 42). In an instructed threat of shock task, cues signalled uncertain threat of shock (50%) or certain safety from shock. Ratings of arousal and valence, skin conductance response (SCR), and functional magnetic resonance imaging were acquired. Overall, participants displayed greater ratings of arousal and negative valence, SCR, and amygdala activation to uncertain threat versus safe cues. IU was not associated with greater arousal ratings, SCR, or amygdala activation to uncertain threat versus safe cues. However, we found that high IU was associated with greater ratings of negative valence and greater activity in the medial prefrontal cortex and dorsomedial rostral prefrontal cortex to uncertain threat versus safe cues. These findings suggest that during cue-signalled uncertainty of threat, individuals high in IU rate uncertain threat as aversive and engage prefrontal cortical regions known to be involved in safety-signalling and conscious threat appraisal. Taken together, these findings highlight the potential of IU in modulating safety-signalling and conscious appraisal mechanisms in situations with cue-signalled uncertainty of threat, which may be relevant to models of anxiety-related pathology.

对不确定威胁的增强反应被认为是焦虑症病理学的一个标志。我们试图确定自我报告的不确定性不耐受（IU）的个体差异，这是焦虑相关病理学中的一个关键跨诊断维度，是否是在提示信号的威胁不确定性期间神经回路的差异募集的基础（n= 42)。在指示的电击威胁任务中，提示表示不确定的电击威胁 (50%) 或一定的电击安全性。获得了唤醒和效价、皮肤电导反应 (SCR) 和功能磁共振成像的评级。总体而言，参与者对不确定的威胁与安全提示的唤醒和负效价、SCR 和杏仁核激活的评分更高。IU 与更高的唤醒等级、SCR 或杏仁核激活与不确定威胁与安全提示无关。然而，我们发现高 IU 与内侧前额叶皮层和背内侧喙前额叶皮层负效价的更高评级和更大的活动相关，以应对不确定的威胁与安全线索。这些发现表明，在威胁的提示信号不确定性期间，IU 高的人将不确定的威胁视为厌恶，并参与已知参与安全信号和有意识威胁评估的前额皮质区域。总之，这些发现强调了 IU 在具有提示信号的威胁不确定性的情况下调节安全信号和有意识评估机制的潜力，这可能与焦虑相关病理学模型有关。