Neurobehavioral mechanisms of human fear generalization

Abstract

While much research has elucidated the neurobiology of fear learning, the neural systems supporting the generalization of learned fear are unknown. Using functional magnetic resonance imaging (fMRI), we show that regions involved in the acquisition of fear support the generalization of fear to stimuli that are similar to a learned threat, but vary in fear intensity value. Behaviorally, subjects retrospectively misidentified a learned threat as a more intense stimulus and expressed greater skin conductance responses (SCR) to generalized stimuli of high intensity. Brain activity related to intensity-based fear generalization was observed in the striatum, insula, thalamus/periacqueductal gray, and subgenual cingulate cortex. The psychophysiological expression of generalized fear correlated with amygdala activity, and connectivity between the amygdala and extrastriate visual cortex was correlated with individual differences in trait anxiety. These findings reveal the brain regions and functional networks involved in flexibly responding to stimuli that resemble a learned threat. These regions may comprise an intensity-based fear generalization circuit that underlies retrospective biases in threat value estimation and overgeneralization of fear in anxiety disorders.

Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research

“…Lissek, Bradford, et al (2014) investigated the brain mechanisms of fear generalization using a version of the "rings of varying size" paradigm. Results replicated previous fMRI investigations of fear generalization in humans (Dunsmoor, Prince, et al, 2011;Greenberg et al 2013a,b), revealing a ("positive") gradient in bilateral insula to stimuli resembling the CS+, and a ("negative") gradient in vmPFC to stimuli more closely approximating the CS-. Positive gradients were also found in the dorsomedial prefrontal cortex and bilateral inferior parietal lobule, while negative gradients were found in bilateral hippocampus and precuneus.…”

“…In a follow-up fMRI investigation, intensity biases were revealed in brain regions implicated in the acquisition of conditioned fear (CS+ versus CS-) including the insula, thalamus, and striatum (Dunsmoor, Prince, et al, 2011). That is, activity in these regions was enhanced to generalized stimuli of high intensity after, but not before, fear conditioning to a CS+ of intermediate intensity.…”

“…The first fMRI study of fear generalization in humans incorporated a perceptual dimension of emotional faces and demonstrated generalized increases in activity to stimuli approximating the CS+ within regions implicated in the acquisition and expression of conditioned fear, including the insula, caudate, and thalamus (Dunsmoor, Prince, et al, 2011). The ventromedial prefrontal cortex (vmPFC), in contrast, showed generalized activity to a stimulus approximating the CS-(see the section on Intensity Generalization below for further details).…”

An Experimental Approach to Examining Psychological Contributions to Multisite Musculoskeletal Pain

“…In recent research, the 'generalization' of fear of pain has been suggested as a mechanism by which fear might contribute to the spreading of pain 15, 45, 46 .…”

“…Generalization of fear of pain occurs when the expectation of a painful sensation is associated with a stimulus that resembles, but is not identical to, the original stimulus 15 . Generalization of fear of pain is believed to be associated with increased and sustained vigilance for pain, as a result of deficient safety learning 14, 40 .…”