Using Virtual Reality to Induce and Assess Objective Correlates of Nicotine Craving: Paradigm Development Study

Background: Craving is a clinically important phenotype for the development and maintenance of nicotine addiction. Virtual reality (VR) paradigms are successful in eliciting cue-induced subjective craving and may even elicit stronger craving than traditional picture-cue methods. However, few studies have leveraged the advances of this technology to improve the assessment of craving. Objective: This report details the development of a novel, translatable VR paradigm designed to both elicit nicotine craving and assess multiple eye-related characteristics as potential objective correlates of craving. Methods: A VR paradigm was developed, which includes three Active scenes with nicotine and tobacco product (NTP) cues present, and three Neutral scenes devoid of NTP cues. A pilot sample (N=31) of NTP users underwent the paradigm and completed subjective measures of nicotine craving, sense of presence in the VR paradigm, and VR-related sickness. Eye-gaze fixation time (“attentional bias”) and pupil diameter toward Active versus Neutral cues, as well as spontaneous blink rate during the Active and Neutral scenes, were recorded. Results: The NTP Cue VR paradigm was found to elicit a moderate sense of presence (mean Igroup Presence Questionnaire score 60.05, SD 9.66) and low VR-related sickness (mean Virtual Reality Sickness Questionnaire score 16.25, SD 13.94). Scene-specific effects on attentional bias and pupil diameter were observed, with two of the three Active scenes eliciting greater NTP versus control cue attentional bias and pupil diameter (Cohen d=0.30-0.92). The spontaneous blink rate metrics did not differ across Active and Neutral scenes. Conclusions: This report outlines the development of the NTP Cue VR paradigm. Our results support the potential of this paradigm as an effective laboratory-based cue-exposure task and provide early evidence of the utility of attentional bias and pupillometry, as measured during VR, as useful markers for nicotine addiction.

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