Neural signatures of spontaneous transitions between internal and external thought

The human mind constantly shifts between internal representations and the external environment, yet the neural mechanisms underlying such spontaneous transitions remain underexplored. Here, we analyzed a think-aloud functional magnetic resonance imaging dataset, in which participants continuously verbalized their thoughts, to identify neural activity predicting transitions between internally and externally oriented thought. Internal-to-external transitions were preceded by increased activation in the salience/ventral attention network, with the strongest effect observed in the right temporoparietal junction. The spatial pattern of this pre-transition activation was positively associated with acetylcholine receptor density, suggesting a role for cholinergic signaling in cognitive reorientation. Pre-transition activation was itself preceded by a large-scale brain state proposed to serve as a flexible hub between functionally specialized states, indicating that spontaneous transitions are more likely when the brain occupies this intermediate configuration. Together, these findings suggest that multilevel neural mechanisms support flexible reorientation along the internal-external dimension of spontaneous cognition.