Disruption of the reconsolidation of conditioned fear memories has been suggested as a non-pharmacological means of preventing the return of learned fear in human populations. A reconsolidation update paradigm was developed in which a reconsolidation window is opened by a single isolated retrieval trial of a previously reinforced CS+ which is then followed by Extinction Training within that window. However, follow-up studies in humans using multi-methods fear conditioning indices (e.g., fear-potentiated startle, skin conductance, US-expectancy) have failed to replicate the retrieval + extinction effects. In the present study, we further investigated the retrieval + extinction reconsolidation update paradigm by directly comparing the acquisition, extinction, and return of fear-potentiated startle in the absence or presence of US-expectancy measures (using a trial-by-trial response keypad) with and without retrieval of a previously acquired CS-US association. Participants were fear conditioned to two visual cue CS+'s, one of which was presented as a single, isolated retrieval trial before Extinction Training and one that was extinguished as usual. The results show that the inclusion of US-expectancy measures strengthens the CS–US association to provide enhanced fear conditioning and maintenance of fear memories over the experimental sessions. In addition, in the groups that used on-line US-expectancy measures, the retrieval + extinction procedure reduced reinstatement of fear-potentiated startle to both previously reinforced CS+'s, as compared to the extinction as usual group.

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Fear conditioning methodologies have often been employed as testable models for assessing learned fear responses in individuals with anxiety disorders such as post-traumatic stress disorder (PTSD) and specific phobia. One frequently used paradigm is measurement of the acoustic startle reflex under conditions that mimic anxiogenic and fear-related conditions. For example, fear-potentiated startle is the relative increase in the frequency or magnitude of the acoustic startle reflex in the presence of a previously neutral cue (e.g., colored shape; termed the conditioned stimulus or CS+) that has been repeatedly paired with an aversive unconditioned stimulus (e.g., airblast to the larynx). Our group has recently used fear-potentiated startle paradigms to demonstrate impaired fear extinction in civilian and combat populations with PTSD. In the current study, we examined the use of either auditory or visual CSs in a fear extinction protocol that we have validated and applied to human clinical conditions. This represents an important translational bridge in that numerous animal studies of fear extinction, upon which much of the human work is based, have employed the use of auditory CSs as opposed to visual CSs. Participants in both the auditory and visual groups displayed robust fear-potentiated startle to the CS+, clear discrimination between the reinforced CS+ and non-reinforced CS−, significant extinction to the previously reinforced CS+, and marked spontaneous recovery. We discuss the current results as they relate to future investigations of PTSD-related impairments in fear processing in populations with diverse medical and psychiatric histories.

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.