Neurocircuitry of Generalization of Avoidance Behavior following Pavlovian Conditioning in Adults with High and Low Trait Anxiety

Abstract

One of the cardinal features of many anxiety disorders is maladaptive avoidance. While behavioral avoidance is important for survival and adaptive when danger is present, in the absence of a threat it is maladaptive. Signaled avoidance depends on Pavlovian learning that a neutral conditioned stimulus signals an ensuing aversive unconditioned stimulus. Maladaptive signaled avoidance could therefore result from abnormalities in Pavlovian conditioning. Overgeneralization of conditioned fear is one such abnormality that has been demonstrated in several anxiety disorders. To assess the relationship between anxiety and generalization of signaled avoidance behavior, 22 participants, with a range of trait anxiety scores split into two group of high and low anxiety, completed a generalization gradient, approach-avoidance fMRI task following Pavlovian discrimination conditioning. Results indicated the expected curvilinear generalization gradient in avoidance responses and ratings of risk, with group differences in avoidance responses. There were several functional regions of interest which also demonstrated the expected curvilinear gradient as well as group differences in percent BOLD signal change across the gradient. This was true for both Pavlovian trials, as well as during the decision making stage of the Instrumental trials. There were also several regions in which activations were significantly related to avoidance behavior. These results indicate that individuals with higher levels of trait anxiety are at increased risk of ‘maladaptive’ avoidance of safe stimuli that resemble danger-cues. Moreover brain areas such as the anterior insula and subgenual anterior cingulate cortex, and primary visual cortex, which are involved in the Pavlovian generalization of fear, are also involved in the overgeneralization of the avoidance response. Additional unexpected findings highlight the role of the cerebellum, somatosensory cortex, and gender in production and maintenance of an avoidance response.