Differential excitatory-inhibitory balance within dorsolateral prefrontal cortex links inter-network interactions in working memory

Abstract Working memory involves complex activity and interactions across multiple brain areas. However, little is known about how these large-scale activity and interaction patterns relate to resting-state activity and to excitatory and inhibitory interactions within localized brain regions. Here we show, using multimodal neuroimaging and large-scale neural network modelling, that excitatory and inhibitory neuronal activities within the dorsolateral prefrontal cortex (DLPFC) are linked to inter-network interactions during working memory. We generate testable predictions by perturbing a resting-state functional magnetic resonance imaging (fMRI)-constrained neural network model and by performing molecular-enriched analyses using fMRI and positron emission tomography (PET) receptor maps. We then show that frontoparietal and default-mode network activity, which differs between resting state and working memory, covaries with DLPFC activity and its functional interactions with these networks. These findings provide a mechanistic account of how local excitatory and inhibitory activity may support large-scale network dynamics involved in working memory.