Impairing existing declarative memory in humans by disrupting reconsolidation

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.forgetting | human memory | misinformation effect | testing effect | eyewitness memory T he entrenched view that memory becomes permanent upon consolidation has faced considerable scrutiny based on recent works demonstrating that retrieval can destabilize existing memories, and that the reactivated memories need to be reconsolidated (1, 2). During the past decade, a growing body of evidence has revealed the chemical and molecular nature of reconsolidation and its behavioral consequences (3). Critically, when a consolidated memory (e.g., a conditioned fear response) is retrieved, it becomes labile and requires protein synthesis for restabilization, and later retrieval of that memory can be severely impaired if an amnesic treatment is administered during the reconsolidation process.Despite the proliferation of research on reconsolidation, few studies have involved human subjects, perhaps because most pharmacological consolidation blockers are unsuitable for human use (3, 4). When reconsolidation associated memory impairments are demonstrated in humans, the effects have been limited to fear conditioning (5-8), motor sequence learning (9), and drug-induced craving (10). To date, we are aware of no study that has shown reconsolidation-associated impairment in declarative memory. Indeed, even when oral administration of propranolol (a systemic pharmacological consolidation blocker approved for human use) reduced the emotional response associated with a fear-inducing experience (6, 7), it left the declarative recollection intact.* Although several studies have examined whether existing declarative memories can be impaired by interference upon reactivation, none has shown memory impairments similar to those regularly exhibited in fear conditioning. Moreover, these studies used a reminder to trigger reactivation of the original memory while pro...

Postretrieval new learning does not reliably induce human memory updating via reconsolidation

“…Therefore, it would appear that the accuracy impairment in the Reminder group was contingent on the time-dependent interaction of the reminder and intervention as demonstrated in similar nonhuman animal studies (1) and widely accepted as evidence for reconsolidation (2,4,6). Consistent with the view that the Old Sequence memory trace had been rewritten by the new learning (12,17), the authors suggested that reconsolidation may have "functional significance," allowing the "continued refinement and reshaping of previously learned movement skills" (ref. 27, p. 618).…”

“…The findings of our conceptual replications cast further doubt on the veracity of claims that memory updating can be mediated by reconsolidation processes (12,(14)(15)(16)(17). These experiments adhered to the canonical 3-day reconsolidation protocol and aimed to increase external validity through the use of sequences similar in structure to phone numbers or computer passwords.…”

“…The absence of reconsolidation effects in all four direct replications suggests that the considerable theoretical weight attributed to the original study (2,4,6,13,14) is unwarranted. Furthermore, the absence of retrieval-contingent impairment in the conceptual replications is inconsistent with the purported functional role of reconsolidation as an adaptive mechanism that underlies memory updating (12,(14)(15)(16)(17). Replication will be an essential tool in future reconsolidation investigations as researchers seek to verify the reliability of existing findings, identify genuine boundary conditions, and foster theoretical progress.…”

“…11). Furthermore, reconsolidation-like effects have been reported when the reminder involves reinforced trials (and thus no prediction error) in both nonhuman animals (47) and humans (12), and impairment effects are absent even in studies where prediction error would be expected (44,45). At present, therefore, it is unclear whether prediction error is either necessary or sufficient for reconsolidation effects to emerge.…”

“…Although physiological interventions are intended to directly disrupt the putative molecular substrates of reconsolidation, considerable ambiguity surrounds the envisioned mechanism by which a behavioral intervention might influence these same processes. Nevertheless, there are prevalent claims about the functional role of reconsolidation as a memory "updating" mechanism (14-16) whereby existing memory traces are selectively "rewritten" by postretrieval new learning (12,17).…”