Spatiotemporal dissociation of brain network connectivity in salience processing: A simultaneous pupillometry-EEG-fMRI study

The processing of salient stimuli involves a wide range of both bottom-up and top-down processes. Previous neuroimaging studies have identified multiple brain areas and networks for salience processing, including the salience network (SN), dorsal attention network (DAN), and the locus coeruleus-norepinephrine (LC-NE) neuromodulatory system. However, interactions among these networks and the cortico-subcortical systems in salience processing remain unclear. Here, we simultaneously recorded pupillometry, electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI) during an auditory oddball paradigm. Using EEG-informed fMRI analysis, we temporally dissociated the target stimulus evoked activation, allowing us to identify the cascades of cortical areas associated with salience processing. Furthermore, functional connectivity analysis uncovered spatiotemporal functional network organizations of these salience processing neural correlates. Using pupillometry as a psychophysiological marker of LC-NE activity, we also assessed brain-pupil relationships. With state-space modeling of target modulated effective connectivity, we found that the target evoked pupillary response is associated with the network causal couplings from late to early subsystems, as well as the network switching initiated by the SN. These findings indicate that the SN might cooperate with pupil-indexed brainstem neuromodulatory systems, such as the LC-NE system, in the reorganization and dynamic switching of cortical networks, and shed light on the implications of their integrative framework in various cognitive processes and neurological diseases.