ABSTRACT The present study investigated the neuromodulatory substrates of salience processing and its impact on memory encoding and behaviour, with a specific focus on two distinct types of salience: reward and contextual unexpectedness. 46 Participants performed a novel task paradigm modulating these two aspects independently and allowing for investigating their distinct and interactive effects on memory encoding while undergoing high‐resolution fMRI. By using advanced image processing techniques tailored to examine midbrain and brainstem nuclei with high precision, our study additionally aimed to elucidate differential activation patterns in subcortical nuclei in response to reward‐associated and contextually unexpected stimuli, including distinct pathways involving in particular dopaminergic modulation. We observed a differential involvement of the ventral striatum, substantia nigra (SN) and caudate nucleus, as well as a functional specialisation within the subregions of the cingulate cortex for the two salience types. Moreover, distinct subregions within the SN in processing salience could be identified. Dorsal areas preferentially processed salience related to stimulus processing (of both reward and contextual unexpectedness), and ventral areas were involved in salience‐related memory encoding (for contextual unexpectedness only). These functional specialisations within SN are in line with different projection patterns of dorsal and ventral SN to brain areas supporting attention and memory, respectively. By disentangling stimulus processing and memory encoding related to two salience types, we hope to further consolidate our understanding of neuromodulatory structures' differential as well as interactive roles in modulating behavioural responses to salient events.

Decoding Salience: A Functional Magnetic Resonance Imaging Investigation of Reward and Contextual Unexpectedness in Memory Encoding and Retrieval