Temporal Dynamics of Large-Scale Networks Predict Neural Cue Reactivity and Cue-Induced Craving

Cue reactivity, a core characteristic of substance use disorders, commonly recruits brain regions that are key nodes in neurocognitive networks, including the default mode network (DMN) and salience network (SN). Whether resting-state temporal dynamic properties of these networks relate to subsequent cue reactivity and cue-induced craving is unknown.

The resting-state data of 46 nicotine-dependent participants were assessed to define temporal dynamic properties of DMN and SN states. Temporal dynamics focused on the total time across the scan session that brain activity resides in these specific states. Using regression models, we examined how the total time in each state related to neural reactivity to smoking cues within key DMN (posterior cingulate cortex, medial prefrontal cortex) or SN (anterior insula, dorsal anterior cingulate cortex) nodes. Mediation analyses were subsequently conducted to study how neural cue reactivity mediates the relationship between total time in state at rest and subjective cue-induced craving.

Increased time spent in the DMN state and decreased time spent in the SN state predicted subsequent cue-induced increases in the anterior insula and dorsal anterior cingulate cortex, respectively. Cue-induced anterior insula and dorsal anterior cingulate cortex activity significantly mediated the relationship between time spent in DMN/SN and cue-induced subjective craving.

Our findings showed a significant relationship between resting-state dynamics of the DMN/SN and task-activated SN nodes that together predicted cue-induced craving changes in nicotine-dependent individuals. These findings propose a neurobiological pathway for cue-induced craving that begins with resting-state temporal dynamics, suggesting that brain responding to external stimuli is driven by resting temporal dynamics.