The neural dynamics of fear memory

While much of what we learn will be forgotten over time, fear memory appears to be particularly resilient to forgetting. Our understanding of how fearful events are transformed into durable memory, and how this memory subsequently influences the processing of (novel) stimuli, is limited. Studying fear memory is complicated by the fact that we cannot directly observe memory, but have to infer it from the different ways it is expressed. Yet, only a small portion of what is concurrently happening in our brain is translated into observable actions and peripheral physiology, or is verbally accessible. Hence, there is a notable discrepancy between the expression of fear during learning and the formation and expression of a fear memory. In this thesis, we used a variety of methods to identify indices that capture the complexity of human fear memory, combining several experimental procedures (Pavlovian fear conditioning, a pharmacological manipulation, and a perceptual judgment task) with behavioral and neural indices of fear (BOLD-MRI, pupil dilation, fear potentiated startle, and subjective reports). To specifically gauge the dynamic nature of fear (un)learning and memory, we developed a single-trial application of multi-voxel pattern analysis (MVPA), a technique that evaluates distributed patterns of BOLD-MRI. We disentangled learning and memory processes by testing on different days and varied contextual cues to (de)activate specific memories. Our findings provide new insights into the different levels at which fear associations emerge, reside and become activated, offering a framework to examine the conditions under which fear learning results in long-lasting fear memory.