Aversive generalization in human amygdala neurons.

Abstract

Generalization around aversive stimuli is a key feature of learning and adaptive decision making,^1,2,3,4,5 but it can be maladaptive if subjects overgeneralize and respond with fear to stimuli that are only loosely similar to the original experience.^{6,7,8,9,10,11,12} Human imaging studies indicate that the amygdala, a hub of emotional learning, is involved in such overgeneralization,^{2,9,13,14,15,16,17} and studies in animal models revealed neural correlates of generalized aversive stimuli and identified changes in response properties of single neurons.^{18,19,20,21,22,23,24,25,26,27,28,29} Yet, it remains unclear if human neurons contribute specifically in aversive situations and, importantly, if they contribute to subsequent behavior even in a safe environment. We recorded single neurons in human subjects while they engaged in probabilistic loss/gain conditioning, followed by a choice task that included additional stimuli and when the original conditioned stimulus no longer entails an aversive (loss) outcome. We find wider behavioral generalization around the aversive stimulus accompanied by a selective increase in amygdala neural responses that were correlated with the degree of individual generalization. In addition, neural activity in the amygdala was predictive of the later choice on a trial-by-trial basis and specific to loss trials. Whereas other brain regions also modulated their activity during generalization, only amygdala neurons signal a trial-specific and loss-specific generalization. The findings reveal that human amygdala neurons play a role in aversive overgeneralization and contribute to generalized choice behavior in a later safe environment and suggest a single-neuron substrate that might enhance anxious and traumatic behaviors.