Fear memory uncovered: Prediction error as the key to memory plasticity

Anxiety disorders rank among the most prevalent and chronic forms of psychopathology. While commonly used therapeutic techniques such as exposure therapy are effective in reducing fear, many patients suffer from relapse of fear. This can be explained by the observation that during therapy a new memory is formed that transiently suppresses the original fear memory. According to the traditional view on memory, once an emotional memory has been stored in the brain through the process of consolidation, the memory remains as a permanent trace. Fear reduction was hence considered to be established only through inhibition - but not elimination - of the fear memory. However, exciting insights from neuroscience have shown that by reactivating a consolidated fear memory, it can return to a plastic state. From this plastic state the memory has to reconsolidate in order to endure. The finding that fear memory is more malleable than previously thought is very promising for clinical practice. Nevertheless, the conditions under which reconsolidation does and does not take place remain to be elucidated. In a series of human fear conditioning experiments we investigated the conditions under which a reactivated memory remains stable or is open to modification. With the demonstration that new learning is a prerequisite for reconsolidation, the current thesis shows that memory reconsolidation allows for memory updating. These findings are of relevance for the mechanisms underlying learning and memory by demonstrating the unique role reconsolidation holds in memory plasticity. Clinical practice will hopefully benefit from these insights in the development of new reconsolidation-based therapies for those who suffer from anxiety disorders and PTSD.