Individuals may show different responses to stressful events. Here, we investigate the neurobiological basis of stress resilience, by showing that neural responsitivity of the noradrenergic locus coeruleus (LC-NE) and associated pupil responses are related to the subsequent change in measures of anxiety and depression in response to prolonged real-life stress. We acquired fMRI and pupillometry data during an emotional-conflict task in medical residents before they underwent stressful emergency-room internships known to be a risk factor for anxiety and depression. The LC-NE conflict response and its functional coupling with the amygdala was associated with stress-related symptom changes in response to the internship. A similar relationship was found for pupil-dilation, a potential marker of LC-NE firing. Our results provide insights into the noradrenergic basis of conflict generation, adaptation and stress resilience.

Confidence, the subjective estimate of decision quality, is a cognitive process necessary for learning from mistakes and guiding future actions. The origins of confidence judgments resulting from economic decisions remain unclear. We devise a task and computational framework that allowed us to formally tease apart the impact of various sources of confidence in value-based decisions, such as uncertainty emerging from encoding and decoding operations, as well as the interplay between gaze-shift dynamics and attentional effort. In line with canonical decision theories, trial-to-trial fluctuations in the precision of value encoding impact economic choice consistency. However, this uncertainty has no influence on confidence reports. Instead, confidence is associated with endogenous attentional effort towards choice alternatives and down-stream noise in the comparison process. These findings provide an explanation for confidence (miss)attributions in value-guided behaviour, suggesting mechanistic influences of endogenous attentional states for guiding decisions and metacognitive awareness of choice certainty.

The locus coeruleus (LC) is a brainstem structure that sends widespread efferent projections throughout the mammalian brain. The LC constitutes the major source of noradrenaline (NE), a modulatory neurotransmitter that is crucial for fundamental brain functions such as arousal, attention, and cognitive control. This role of the LC-NE is traditionally not believed to reflect functional influences on the frontoparietal network or the striatum, but recent advances in chemogenetic manipulations of the rodent brain have challenged this notion. However, demonstrations of LC-NE functional connectivity with these areas in the human brain are surprisingly sparse. Here, we close this gap. Using an established emotional stroop task, we directly compared trials requiring response conflict control with trials that did not require this, but were matched for visual stimulus properties, response modality, and controlled for pupil dilation differences across both trial types. We found that LC-NE functional coupling with the parietal cortex and regions of the striatum is substantially enhanced during trials requiring response conflict control. Crucially, the strength of this functional coupling was directly related to individual reaction time differences incurred by conflict resolution. Our data concur with recent rodent findings and highlight the importance of converging evidence between human and nonhuman neurophysiology to further understand the neural systems supporting adaptive and maladaptive behavior in health and disease.