The influence of acoustic startle probes on fear learning in humans

Michelle I C De Haan,Sonja Van Well,H Steven Scholte,Merel Kindt,Renée M Visser,Guido A Van Wingen

doi:10.1038/s41598-018-32646-1

Abstract

Even though human fear-conditioning involves affective learning as well as expectancy learning, most studies assess only one of the two distinct processes. Commonly used read-outs of associative fear learning are the fear-potentiated startle reflex (FPS), pupil dilation and US-expectancy ratings. FPS is thought to reflect the affective aspect of fear learning, while pupil dilation reflects a general arousal response. However, in order to measure FPS, aversively loud acoustic probes are presented during conditioning, which might in itself exert an effect on fear learning. Here we tested the effect of startle probes on fear learning by comparing brain activation (fMRI), pupil dilation and US-expectancy ratings with and without acoustic startle probes within subjects. Regardless of startle probes, fear conditioning resulted in enhanced dACC, insula and ventral striatum activation. Interaction analyses showed that startle probes diminished differential pupil dilation between CS+ and CS− due to increased pupil responses to CS−. A trend significant interaction effect was observed for US-expectancy and amygdala activation. Startle probes affect differential fear learning by impeding safety learning, as measured with pupil dilation, a read-out of the cognitive component of fear learning. However, we observed no significant effect of acoustic startle probes on other measures of fear learning.

Highlights

While fear conditioning involves both affective and cognitive learning, few studies include read-outs of both cognitive and affective learning
In addition to the overall effect of fear conditioning, we found that acoustic startle probes influenced pupil dilation by increasing pupil responses to the conditioned stimulus (CS)−, and we found a trend significant interaction between Stimulus and Condition in unconditioned stimulus (US)-expectancy ratings and in brain activation in the amygdala
Acoustic startle probes were administered on every Probe trial, but a task with a partial scheme is likely to show the same effect because the anticipation of the acoustic startle probe causes the increase in pupil dilation for the CS−

Summary

Introduction

While fear conditioning involves both affective and cognitive learning, few studies include read-outs of both cognitive and affective learning. Evidence of fear learning in humans is usually obtained through behavioral and physiological measures of the expression of fear, such as the fear-potentiated startle (FPS) reflex, pupil dilation, skin conductance response and US-expectancy ratings and fMRI9. We examined the influence of startle probes on both behavioral and neural read-outs of fear learning, by simultaneously assessing brain activation (fMRI), affective learning (FPS) and expectancy learning (retrospective US-expectancy ratings and pupil dilation) during fear conditioning. We assessed the effect of acoustic startle probes on brain activation (both whole brain and in specific regions of interest (ROIs); the dACC, insula, ventral striatum, thalamus, midbrain/dorsal pons and amygdala separately) and pupil dilation during fear conditioning and on retrospective US-expectancy ratings. As CSs we used pictures of neutral faces with two separate categories (i.e., age: adult vs. child and sex: male vs. female) both categories consisted of a CS+ and a CS− stimulus, but only one category was paired with acoustic startle probes (Fig. 1)

Methods

Results

Conclusion