Generalization of fear-potentiated startle in the presence of auditory cues: a parametric analysis

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.

Keywords: auditory perception; fear conditioning; generalization; startle response; stimulus; translational medical research.

Figure 1

Participants displayed robust fear-potentiated startle to the CS+ as compared to the noise probe alone (NA; panel A) and discrete discrimination between the CS+ and CS− based on fear-potentiated startle responses (panel B) and US expectancy ratings (panel C). Difference Score = [startle magnitude to the CS] − [startle magnitude to the noise probe alone]. *** p ≤ 0.001.

Figure 2

In Experiment 1, participants displayed significant discrimination between the CS+ and CS- during the Re-training phase as measured by fear-potentiated startle (panel A) and US expectancy (panel B). A generalization gradient was evident when examining fear-potentiated startle to the previously reinforced CS+ and the GS two steps away from the CS+ (2000 Hz). There was no significant difference between the previously reinforced CS+ and the two adjacent GSs (250 and 1000 Hz). Based on US expectancy ratings, participants displayed clear retention of the excitatory properties of the previously reinforced CS+ and a generalization gradient was evident when examining expectancy ratings from the previously reinforced CS+ and the GS two steps away from the CS+ (2000 Hz). Difference Score = [startle magnitude to the CS] − [startle magnitude to the noise probe alone]. *p< 0.05; ***p ≤ 0.001.

Figure 3

Follow-up Experiment 2 was aimed at better understanding the point at which generalization occurs in this auditory stimulus generalization paradigm. When the GSs differed from the previously reinforced CS+ by 2000 and 4000 Hz (maintaining octave intervals), there was a significant difference between the previously reinforced CS+ and the two GSs on both fear-potentiated startle responses (panel A) and US expectancy (panel B). Difference Score = [startle magnitude to the CS] − [startle magnitude to the noise probe alone]. * p < 0.05; ** p < 0.01; *** p ≤ 0.001.