What does it take to demonstrate memory erasure? Theoretical comment on Norrholm et al. (2008).

Behavioral and pharmacological approaches to strengthen the long-term consequences of a learning experience often focus on ways of enhancing memory formation. This approach has been successful at strengthening new memories that form as a result of an initial learning experience (e.g., McGaugh, 2004). It also has been successful at strengthening processes involved in extinction, resulting in the rapid and persistent loss of a previously established conditioned response(e.g., Walker, Ressler, Lu, & Davis, 2002). Extinction has been a particularly interesting process to strengthen because behavioral enhancements in extinction may occur by facilitating the development of some new learning process during extinction, or by impairing some process associated with the neural representation of the original memory (see Lattal, Radulovic, & Lukowiak, 2006; Myers & Davis, 2007). Several recent studies have characterized some of the behavioral and molecular conditions that may favor memory erasure (or unlearning) as a mechanism for extinction. These findings are provocative, but there are many reasons to be cautious about interpreting any extinction effect as being caused by memory erasure. Although extinction is commonly described as a learning process that involves new memory formation, theories of extinction have indeed sometimes appealed to erasure mechanisms to explain aspects of extinction (e.g., Estes 1950; reviewed in Delamater, 2004; Rescorla, 2004). This idea that extinction may sometimes erase the original memory is explored in the experiments reported by Norrholm, Vervliet, Jovanovic, Boshoven, Myers, Davis, & Rothbaum (2008). Their approach is particularly noteworthy because they take a commonly used behavioral paradigm with rodents and extend it to humans. This enables them to ask questions about similar mechanisms between humans and rodents, and, more important for studies of extinction, this preparation allows Norrholm et al (2008) to examine how the behavioral response corresponds to subjects’ self-reported knowledge of the stimulus contingencies (revealed through an expectancy measure). Although the expectancy measure is not without complications, it gives the subjects two possible ways to answer the question, “Do you remember the initial contingencies?” Norrholm et al (2008) show that the answer to this question may be “no” when conditioned responses are examined, but it may be “yes” when expectancy measures are used. The designs of Norrholm et al’s extinction experiments are based on a key assumption that underlies many neurobiological accounts of memory, which is that a behavioral experience instigates a cascade of cellular and molecular events that consolidate an experience into a relatively stable, permanent memory (reviewed in McGaugh, 2000). This consolidation process can be impaired or enhanced by any number of pharmacological and behavioral interventions, provided those interventions occur in close proximity to the learning experience. One of these interventions may potentially include an extinction trial – if extinction occurs soon after acquisition (immediate extinction), the extinction memory may override or compete with the initial memory for consolidation, resulting in a permanently weakened initial memory (e.g., Myers, Ressler, & Davis, 2006). Norrholm et al (2008) demonstrate that although immediate extinction may weaken spontaneous recovery of a conditioned fear response, it does not prevent recovery of expectancy ratings. This difference emphasizes the importance of asking questions about extinction and memory erasure in multiple ways. Because a number of recent studies have suggested that extinction may involve unlearning mechanisms, it is important to give careful thought to the kind of evidence needed to demonstrate memory erasure. This needs to be considered in the context of extinction, as well as in the context of reconsolidation, where pharmacological interventions after a brief extinction trial may permanently erase (or enhance, depending on the intervention) the original memory. All of the studies that demonstrate memory erasure make compelling cases based on behavioral and molecular results, but they are faced with the same inherent challenge. That is, what are the behavioral and molecular mechanisms underlying memory formation and storage? Until we have a full understanding of the external and internal circumstances that cause memory formation, we will be hard pressed to conclude that any manipulation has retroactively eliminated that memory.