Impairing existing declarative memory in humans by disrupting reconsolidation

Jason C. K. Chan; Jessica A. LaPaglia

doi:10.1073/pnas.1218472110

Edited by Robert Desimone, Massachusetts Institute of Technology, Cambridge, MA, and approved April 23, 2013 (received for review October 23, 2012)

Abstract

During the past decade, a large body of research has shown that memory traces can become labile upon retrieval and must be restabilized. Critically, interrupting this reconsolidation process can abolish a previously stable memory. Although a large number of studies have demonstrated this reconsolidation associated amnesia in nonhuman animals, the evidence for its occurrence in humans is far less compelling, especially with regard to declarative memory. In fact, reactivating a declarative memory often makes it more robust and less susceptible to subsequent disruptions. Here we show that existing declarative memories can be selectively impaired by using a noninvasive retrieval–relearning technique. In six experiments, we show that this reconsolidation-associated amnesia can be achieved 48 h after formation of the original memory, but only if relearning occurred soon after retrieval. Furthermore, the amnesic effect persists for at least 24 h, cannot be attributed solely to source confusion and is attainable only when relearning targets specific existing memories for impairment. These results demonstrate that human declarative memory can be selectively rewritten during reconsolidation.

Footnotes

↵¹To whom correspondence should be addressed. E-mail: ckchan{at}iastate.edu.

Author contributions: J.C.K.C. and J.A.L. designed research; J.C.K.C. and J.A.L. performed research; J.C.K.C. and J.A.L. analyzed data; and J.C.K.C. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1218472110/-/DCSupplemental.
*A recent study showed that emotional (but not nonemotional) declarative memory might need to reconsolidate upon retrieval (16). However, this study did not obtain overt recall responses from participants during the memory reactivation phase; thus, like many other human studies, it is not possible to ascertain that retrieval was attempted. Moreover, the amnesic treatment (propranolol) was administered orally 1 h before the memory reactivation phase. Therefore, it is possible that, instead of blocking reconsolidation, propranolol exerted an influence on retrieval and produced a permanent effect on the memory (4).
^†To ensure relatively stable results in these conditional analyses, we included data from only participants who recalled at least three items correctly for both the neutral and misinformed items during the reactivation phase. As such, the degrees of freedom for these analyses are smaller than those of the analyses that included all items (df_exp ₁ = 52, df_exp ₃ = 10, df_exp ₄ = 27, df_exp ₆ = 14).