Neurobehavioral mechanisms of human fear generalization

Center for Cognitive Neuroscience, Duke University, Durham, NC 27708-0999, USA.
NeuroImage (Impact Factor: 6.13). 04/2011; 55(4):1878-88. DOI: 10.1016/j.neuroimage.2011.01.041
Source: PubMed

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.

Download full-text


Available from: Steve E Prince, Jun 24, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intense fear responses observed in trauma-, stressor-, and anxiety-related disorders can be elicited by a wide range of stimuli similar to those that were present during the traumatic event. The present study investigated the experimental utility of fear-potentiated startle paradigms to study this phenomenon, known as stimulus generalization, in healthy volunteers. Fear-potentiated startle refers to a relative increase in the acoustic startle response to a previously neutral stimulus that has been paired with an aversive stimulus. Specifically, in Experiment 1 an auditory pure tone (500 Hz) was used as the conditioned stimulus (CS+) and was reinforced with an unconditioned stimulus (US), an airblast to the larynx. A distinct tone (4000 Hz) was used as the nonreinforced stimulus (CS-) and was never paired with an airblast. Twenty-four hours later subjects underwent Re-training followed by a Generalization test, during which subjects were exposed to a range of generalization stimuli (GS) (250, 1000, 2000, 4000, 8000 Hz). In order to further examine the point at which fear no longer generalizes, a follow-up experiment (Experiment 2) was performed where a 4000 Hz pure tone was used as the CS+, and during the Generalization test, 2000 and 8000 Hz were used as GS. In both Experiment 1 and 2 there was significant discrimination in US expectancy responses on all stimuli during the Generalization Test, indicating the stimuli were perceptually distinct. In Experiment 1, participants showed similar levels of fear-potentiated startle to the GS that were adjacent to the CS+, and discriminated between stimuli that were 2 or more degrees from the CS+. Experiment 2 demonstrated no fear-potentiated startle generalization. The current study is the first to use auditory cues to test generalization of conditioned fear responses; such cues may be especially relevant to combat posttraumatic stress disorder (PTSD) where much of the traumatic exposure may involve sounds.
    Frontiers in Behavioral Neuroscience 10/2014; 8:361. DOI:10.3389/fnbeh.2014.00361 · 4.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Socially anxious individuals have been shown to exhibit altered processing of facial affect, especially expressions signaling threat. Enhanced unaware processing has been suggested an important mechanism which may give rise to anxious conscious cognition and behavior. This study investigated whether individuals with social anxiety disorder (SAD) are perceptually more vulnerable to the biasing effects of subliminal threat cues compared to healthy controls. In a perceptual judgment task, 23 SAD and 23 matched control participants were asked to rate the affective valence of parametrically manipulated affective expressions ranging from neutral to angry. Each trial was preceded by subliminal presentation of an angry/neutral cue. The SAD group tended to rate target faces as “angry” when the preceding subliminal stimulus was angry vs. neutral, while healthy participants were not biased by the subliminal stimulus presentation. The perceptual bias in SAD was also associated with higher reaction time latencies in the subliminal angry cue condition. The results provide further support for enhanced unconscious threat processing in SAD individuals. The implications for etiology, maintenance, and treatment of SAD are discussed.
    Frontiers in Human Neuroscience 08/2014; 8. DOI:10.3389/fnhum.2014.00580 · 2.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In humans, activity patterns in the ventromedial prefrontal cortex (vmPFC) have been found to be predictive of subsequent fear memory consolidation. Pioneering work in rodents has further shown that vmPFC-amygdala theta synchronization is correlated with fear memory consolidation. We aimed to evaluate whether vmPFC activity during fear conditioning is (1) correlated with fear expression the subsequent day and whether (2) this relationship is mediated by rapid eye movement (REM) sleep. We analyzed data from 17 young healthy subjects undergoing a fear conditioning task, followed by a fear extinction task 24 h later, both recorded with simultaneous skin conductance response (SCR) and functional magnetic resonance imaging measurements, with a polysomnographically recorded night sleep in between. Our results showed a correlation between vmPFC activity during fear conditioning and subsequent REM sleep amount, as well as between REM sleep amount and SCR to the conditioned stimulus 24 h later. Moreover, we observed a significant correlation between vmPFC activity during fear conditioning and SCR responses during extinction, which was no longer significant after controlling for REM sleep amount. vmPFC activity during fear conditioning was further correlated with sleep latency. Interestingly, hippocampus activity during fear conditioning was correlated with stage 2 and stage 4 sleep amount. Our results provide preliminary evidence that the relationship between REM sleep and fear conditioning and extinction observed in rodents can be modeled in healthy human subjects, highlighting an interrelated set of potentially relevant trait markers.
    Experimental Brain Research 01/2014; 232(5). DOI:10.1007/s00221-014-3831-2 · 2.17 Impact Factor