Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network

The salience network (SN) and default mode network (DMN) play a crucial role in cognitive function. The SN, anchored in the anterior insular cortex (AI), has been hypothesized to modulate DMN activity during stimulus-driven cognition. However, the causal neural mechanisms underlying changes in DMN activity and its functional connectivity with the SN are poorly understood. Here we combine feedforward optogenetic stimulation with fMRI and computational modeling to dissect the causal role of AI neurons in dynamic functional interactions between SN and DMN nodes in the male rat brain. Optogenetic stimulation of Chronos-expressing AI neurons suppressed DMN activity, and decreased AI-DMN and intra-DMN functional connectivity. Our findings demonstrate that feedforward optogenetic stimulation of AI neurons induces dynamic suppression and decoupling of the DMN and elucidates previously unknown features of rodent brain network organization. Our study advances foundational knowledge of causal mechanisms underlying dynamic cross-network interactions and brain network switching.