Modulation of locus coeruleus activity by novel oddball stimuli.

It has long been known from animal literature that the locus coeruleus (LC), the source region of noradrenergic neurons in the brain, is sensitive to unexpected, novel, and other salient events. In humans, however, direct assessment of LC activity has proven to be challenging due to its small size and difficult localization, which is why noradrenergic activity has often been assessed using more indirect measures such as electroencephalography (EEG) and pupil recordings. Here, we combined high-resolution functional magnetic resonance imaging (fMRI) with a special anatomical sequence to assess neural activity in the LC in response to different types of salient stimuli in an oddball paradigm (novel neutral oddballs, novel emotional oddballs, and familiar target oddballs). We found a significant linear increase of LC activity from standard trials, over familiar target oddballs, to novel neutral and novel emotional oddballs. Importantly, when breaking down this linear trend, only novel oddball stimuli led to robust activity increases as compared to standard trials, with no statistical difference between neutral and emotional ones. This pattern suggests that activity modulations in the LC in the present study were mainly driven by stimulus novelty, rather than by emotional saliency, task relevance, or contextual novelty alone. Moreover, the absence of significant activity modulations in response to target oddballs (which were reported in a recent study) suggests that the LC represents relative rather than absolute saliency of a stimulus in its respective context.