Temporal 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. In this cross-sectional study of 102 individuals who smoked nicotine long term matched with 102 healthy controls, individuals who smoked nicotine spent more time in the frontoinsular default mode brain network. Alexithymia mediated the association between childhood trauma and time spent in the frontoinsular default mode network only in individuals who smoked nicotine. The findings suggest that distinct neurobiological profiles noted in those who smoke nicotine are associated with childhood trauma–related alexithymia.