Nicotine acutely alters temporal properties of resting brain states.

Background: Nicotine-dependent individuals have altered activity in neurocognitive networks such as the default mode (DMN), salience (SN) and central executive networks (CEN). One theory suggests that, among chronic tobacco smokers, nicotine abstinence drives more DMN-related internal processing while nicotine replacement suppresses DMN and enhances SN and CEN. Whether acute nicotine impacts network dynamics in non-smokers is, however, unknown.

Methods: In a randomized double-blind crossover study, 17 healthy non-smokers (8 females) were administered placebo and nicotine (2-mg lozenge) on two different days prior to collecting resting-state functional magnetic resonance imaging (fMRI). Previously defined brain states in 462 individuals that spatially overlap with well-characterized resting-state networks including the DMN, SN, and CEN were applied to compute state-specific dynamics at rest: total time spent in state, persistence in each state after entry, and frequency of state transitions. We examined whether nicotine acutely alters these resting-state dynamics.

Results: A significant drug-by-state interaction emerged; post-hoc analyses clarified that, relative to placebo, nicotine suppressed time spent in a frontoinsular-DMN state (posterior cingulate cortex, medial prefrontal cortex, anterior insula, striatum and orbitofrontal cortex) and enhanced time spent in a SN state (anterior cingulate cortex and insula). No significant findings were observed for persistence and frequency.

Conclusions: In non-smokers, nicotine biases resting-state brain function away from the frontoinsular-DMN and toward the SN, which may reduce internally focused cognition and enhance salience processing. While past work suggests nicotine impacts DMN activity, the current work shows nicotinic influences on a specific DMN-like network that has been linked with rumination and depression.