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Background: The global prevalence of smoking remains a significant public health concern, necessitating the development of effective anti-smoking campaigns to promote smoking cessation and discourage smoking initiation. Understanding the factors that influence individual responses to anti-smoking messages is critical for tailoring campaigns to different populations. Focus of the Article: This study substantially exhibits the concepts of audience segmentation and targeting, informed by theory and formative research, and monitoring and evaluation research in the context of anti-smoking campaigns. Research Question: The article aims to answer how smoking behavior and message framing influence individuals' counterarguing responses to anti-smoking advertisements and the implications for ad effectiveness. Approach: The research investigates the role of smoking behavior (smokers vs. non-smokers) and message framing (positive vs. negative) in shaping individuals' counterarguing responses to anti-smoking advertisements, using two studies involving behavioral and neuroscientific methods. Methods: Study 1 employed an online video task with 1920 participants, examining the effects of smoking behavior and message framing on ad effectiveness. Study 2 used electroencephalography (EEG) to record brain activity from 31 participants while they viewed anti-smoking video advertisements, focusing on the neural correlates of counterarguing and their effect on anti-smoking ad effectiveness. Results: Study 1 found that smokers report lower ad effectiveness compared to non-smokers, and observed an interaction between smoking behavior and message framing. Study 2 found that smoking behavior significantly influenced brain activity in the dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (VLPFC), and anterior cingulate cortex (ACC) regions in response to anti-smoking ads. Additionally, a significant interaction was observed between smoking behavior and ad framing on brain activity in all three regions. Recommendations for Research or Practice: The findings suggest that anti-smoking campaigns should be tailored to the specific needs and attitudes of smokers and non-smokers, with separate campaigns for each group. Future research could explore the role of other individual differences in shaping counterarguing responses, the long-term effects of exposure to different types of anti-smoking messages on smoking behavior, and using more advanced neuroimaging techniques to investigate the neural processes that underlie counterarguing responses to anti-smoking messages for better flow. [ABSTRACT FROM AUTHOR]