Effects of Locus Coeruleus Activation on n-Back Performance and Frontoparietal Activity.

Abstract

Previous studies have linked working memory capacity to restricted hemodynamic responses within critical nodes of the frontoparietal network. Emerging evidence suggests a potential role of the locus coeruleus (LC) in modulating activation of key regions essential for working memory function. This study investigated this hypothesis by examining changes in BOLD signal within the LC and cortex during a parametrically designed verbal working memory task (n-back). fMRI revealed load-dependent task activation, with maximum activation of presumed LC neurons positively correlating with working memory capacity. Furthermore, increased hemodynamic responses in the superior parietal lobes and dorsolateral pFC corresponded with the magnitude of LC activation near working memory capacity limits. An exploratory functional connectivity analysis suggests improvements in working memory performance rely on negative functional connectivity between the LC and cortical regions not primarily involved in task completion. On the basis of previous evidence, this association may represent inhibitory input from cortical regions, enabling phasic bursts of activity from LC neurons, thereby facilitating enhanced cortical activation. This result may also indicate noradrenergic suppression of cortical regions that are not crucial for task completion, leading to enhanced network efficiency. These findings suggest a mechanism by which the LC may improve verbal working memory performance by facilitating enhanced activation in regions critical for visual working memory capacity and active maintenance, potentially enhancing network efficiency.