Multidimensional approach to the study of olfactory fear conditioning in individuals with low and high trait anxiety vulnerability

Introduction: Fear conditioning is a fundamental learning mechanism often used to model anxiety reactions across species. Threat-processing anomalies dependent on anxiety vulnerability have been mostly identified in cognition. However, recent evidence stresses the impact of anxiety on even the earlier stages of stimulus perception (sensory processing) and on the physiological and neurophysiological reactions. To experimentally test the effects of fear conditioning, most studies have used audio-visual material even though emotionally salient odors have been proven to produce stronger emotional reactions than visual stimuli, possibly in virtue of their direct access to amygdala and hippocampus. Here we aim to test, with a multidimensional approach, the impact of anxiety vulnerability on perception, physiological arousal, mean neural activations and activation atterns in an odor-based fear conditioning paradigm. Methods: Twenty-one healthy participants were divided in two subgroups on the basis of their low (LAV) or high (HAV) trait anxiety vulnerability. Event-related perceptual ratings of odor intensity (visual analogous scales, VAS), psychophysiological arousal (skin conductance responses, SCR) and functional magnetic resonance imaging were co-registered within participants over a 20-min period in which odor-threat associations were repeatedly induced. Results: Subjective odor intensity increased post-conditioning for both groups, suggesting experience -dependent sensory evaluation processing. Skin conductance responses were heightened for the HAV as compared to the LAV group, favoring the appearance of differential learning (CS+ vs. CS-) post conditioning. Anxiety vulnerability selectively impacted neural processing in areas of the fear network such as amygdala, insula and cingulate cortex. Multivariate pattern analyses of fMRI activity reveal learning-dependent effects on odor representations within both primary (piriform cortex) and secondary olfactory areas (orbitofrontal cortex) over time. Conclusions: These results indicate that anxiety vulnerability differentially and dynamically modulates perceptual, physiological and neural responses to emotionally salient odors. Taken together, these results contribute to the implication of sensory stimuli in the development and maintenance of anxiety disorders.