Sex differences in the resting state brain function of cigarette smokers and links with smoking-related behavior

Open Access
Beltz, Adriene Marie
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
May 02, 2014
Committee Members:
  • Sheri A. Berenbaum, Dissertation Advisor
  • Rick Owen Gilmore, Committee Member
  • Stephen Jeffrey Wilson, Committee Member
  • Peter Cm Molenaar, Special Member
  • sex differences
  • brain function
  • resting state
  • cigarette smoking
  • gender
  • fMRI
Sex matters for drug use, particularly for cigarette smoking – the leading cause of preventable death in the United States. More men than women smoke, but women are less likely than men to quit. Sex differences in smoking behavior contribute to sex differences in cessation, with men more likely to use cigarettes for the pharmacological effects of nicotine and women more likely to smoke for the non-pharmacological effects of cigarettes, in response to learned cues. Brain function is one mechanism underlying these behavioral sex differences, as it is altered by the psychoactive effects of nicotine and facilitates cue-learning. Little is known, however, about the influence of resting state brain function, or intrinsic brain activity that occurs in the absence of a goal-directed task and marks neuropsychiatric disease, on sex differences in smoking behavior. The goal of the current study was to delineate sex differences in the resting state connectivity of three brain networks underlying smoking (default mode, attention, reward), and to determine how sex moderates links from network connectivity to smoking behavior (nicotine dependence, quitting self-efficacy). This goal was accomplished by examining the functional magnetic resonance imaging and behavioral data of 50 regular adult smokers (23 women). Results revealed sex differences favoring women in connectivity within the default mode network and between the default mode and reward networks. Results also suggest that women have difficulty quitting because of a reward network paradox: For women but not for men, increased connectivity within the reward network predicted both increased nicotine dependence and increased quitting self-efficacy, two behaviors that have opposite relations to cessation. Future work should investigate links between connectivity within the reward network and smoking behavior using larger samples that include non-smoking controls and alternative metrics of network connectivity.