Neural substrates of individual differences in human fear learning: evidence from concurrent fMRI, fear-potentiated startle, and US-expectancy data

To provide insight into individual differences in fear learning, we examined the emotional and cognitive expressions of discriminative fear conditioning in direct relation to its neural substrates. Contrary to previous behavioral–neural (fMRI) research on fear learning—in which the emotional expression of fear was generally indexed by skin conductance—we used fear-potentiated startle, a more reliable and specific index of fear. While we obtained concurrent fear-potentiated startle, neuroimaging (fMRI), and US-expectancy data, healthy participants underwent a fear-conditioning paradigm in which one of two conditioned stimuli (CS(+) but not CS(–)) was paired with a shock (unconditioned stimulus [US]). Fear learning was evident from the differential expressions of fear (CS(+) > CS(–)) at both the behavioral level (startle potentiation and US expectancy) and the neural level (in amygdala, anterior cingulate cortex, hippocampus, and insula). We examined individual differences in discriminative fear conditioning by classifying participants (as conditionable vs. unconditionable) according to whether they showed successful differential startle potentiation. This revealed that the individual differences in the emotional expression of discriminative fear learning (startle potentiation) were reflected in differential amygdala activation, regardless of the cognitive expression of fear learning (CS–US contingency or hippocampal activation). Our study provides the first evidence for the potential of examining startle potentiation in concurrent fMRI research on fear learning

The influence of acoustic startle probes on fear learning in humans

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