ImportanceTemporal dynamic measures provide insight into the neurobiological properties of nicotine use. It is critical to determine whether brain-based measures are associated with substance use risk factors, such as childhood trauma–related emotion dysregulation.ObjectiveTo assess temporal dynamic differences based on smoking status and examine the associations between childhood trauma, alexithymia, nicotine smoking, and default mode network (DMN) states.Design, Setting, and ParticipantsThis cross-sectional study was conducted in the Baltimore, Maryland, area at the National Institute on Drug Abuse. Participants included individuals aged 18 to 65 years who smoked nicotine long term and matched controls with no co-occurring substance use or psychiatric disorders. Participants were enrolled from August 8, 2013, to August 9, 2022. Analysis was conducted from August 2022 to July 2023.ExposureLong-term nicotine smoking.Main Outcomes and MeasuresThe main outcome was temporal dynamic differences based on smoking status. Coactivation pattern analysis was conducted based on 16-minute resting-state functional magnetic resonance imaging; total time in, persistence of, and frequency of transitions into states were evaluated. The associations between childhood trauma (Childhood Trauma Questionnaire), alexithymia (20-item Toronto Alexithymia Scale), and DMN temporal dynamics were assessed.ResultsThe sample included 204 participants (102 individuals who smoked nicotine and 102 control individuals) with a mean (SD) age of 37.53 (10.64) years (109 [53.4%] male). Compared with controls, individuals who smoked nicotine spent more time in the frontoinsular DMN (FI-DMN) state (mean difference, 25.63 seconds; 95% CI, 8.05-43.20 seconds; η2p = 0.04; P = .004 after Bonferroni correction). In those who smoked nicotine, greater alexithymia was associated with less time spent in the FI-DMN state (r, −0.26; 95% CI, −0.44 to −0.07; P = .007). In a moderated mediation analysis, alexithymia mediated the association between childhood trauma and time spent in the FI-DMN state only in individuals who smoked nicotine (c′ = −0.24; 95% CI, −0.58 to −0.03; P = .02).Conclusions and RelevanceCompared with controls, individuals who smoked nicotine spent more time in the FI-DMN state. Among those who smoked nicotine, childhood trauma–related alexithymia was associated with less time spent in the FI-DMN state, indicating that considering trauma-related factors may reveal alternative neurobiological underpinnings of substance use. These data may aid in reconciling contradictory findings in prior literature regarding the role of FI-DMN regions in substance use.