Contextual modulation of conditioned responses in humans: A review on virtual reality studies

Conditioned response (CRs) triggered by stimuli predicting aversive consequences have been confirmed across various species including humans, and were found to be exaggerated in anxious individuals and anxiety disorder patients. Importantly, contextual information may strongly modulate such conditioned responses (CR), however, there are several methodological boundaries in the translation of animal findings to humans, and from healthy individuals to patients. Virtual Reality (VR) is a useful technological tool for overcoming such boundaries. In this review, we summarize and evaluate human VR conditioning studies exploring the role of the context as conditioned stimulus or occasion setter for CRs. We observe that VR allows successful acquisition of conditioned anxiety and conditioned fear in response to virtual contexts and virtual cues, respectively. VR studies also revealed that spatial or temporal contextual information determine whether conditioned anxiety and conditioned fear become extinguished and/or return. Novel contexts resembling the threatening context foster conditioned fear but not conditioned anxiety, suggesting distinct context-related generalization processes. We conclude VR contexts are able to strongly modulate CRs and therefore allow a comprehensive investigation of the modulatory role of the context over CR in humans leading to conclusions relevant for non-VR and clinical studies.