Biological psychiatry. Cognitive neuroscience and neuroimaging | 2021
Behavioral and Magnetoencephalographic Correlates of Fear Generalization are Associated with Responses to Later Virtual Reality Exposure Therapy in Spider Phobia.
Abstract
BACKGROUND\nAs overgeneralization of fear is a pathogenic marker of anxiety disorders, we investigated whether pre-treatment levels of fear generalization in spider-phobic patients are related to their response to exposure-based treatment, in order to identify pre-treatment moderators of treatment success.\n\n\nMETHODS\nNinety patients with spider phobia completed pre-treatment clinical and magnetoencephalography (MEG) assessments, one session of virtual reality exposure therapy, and a post-treatment clinical assessment. Based on the primary outcome (30% symptom reduction in self-reported symptoms) they were categorized as responders or non-responders. In a pre-treatment MEG fear generalization paradigm involving fear conditioning with two unconditioned stimuli (UCS), we obtained fear ratings, UCS-expectancy ratings, and event-related fields to conditioned stimuli (CS-, CS+) and 7 different generalization stimuli (GS) on a perceptual continuum from CS- to CS+.\n\n\nRESULTS\nPrior to treatment, non-responders showed behavioral overgeneralization indicated by more linear generalization gradients in fear ratings. Analyses of MEG source estimations revealed that non-responders showed a decline of their (inhibitory) frontal activations to safety-signaling CS- and GS compared to CS+ over time, while responders maintained these activations at early (<300ms) and late processing stages.\n\n\nCONCLUSIONS\nResults provide initial evidence that pre-treatment differences of behavioral and neural markers of fear generalization may act as moderators of later responses to behavioral exposure. Stimulating further research on fear generalization as a potential predictive marker, our findings are an important first step in the attempt to identify patients who may not profit from ET, and to personalize and optimize treatment strategies for this vulnerable patient group.