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“Memories are constantly changing, each time we recall them they're physically different.”
- me, July 7, 2006
The precision of memory over time is a quaint idea. A large body of research shows us that memories are not fixed entities (Alberini & Ledoux, 2013). Every time a specific memory “trace” is reactivated, it enters a transiently unstable state where it's subject to change before becoming consolidated and stored again (Nader & Hardt et al., 2009). In the most widely studied model systems, new protein synthesis in the hippocampus and/or amygdala is required for reconsoldation of fear memories.
Fig. 1 (Alberini & Ledoux, 2013). Two Views of Memory. In the reconsolidation view (bottom), when a memory is activated, the version stored during the last retrieval (rather than the version stored after the original experience) is called up.
Although these concepts and mechanisms of memory reconsolidation are not universally accepted, they've formed the basis for a thriving area of basic neuroscience research. Furthermore, the principles learned from animal studies have been applied to Pavlovian fear conditioning in humans (Schiller et al., 2010).
By precisely timing the presentation of a fear memory reminder (i.e., within the reconsolidation window), extinction of the skin conductance response to a conditioned stimulus (a colored square previously associated with a mild shock) occurred when tested 24 hours later (Schiller et al., 2010). A subset of participants returned one year later, and the “extinction-during-reconsolidation” procedure prevented reinstatement of the fear response, unlike in the group where extinction training was conducted outside the reconsolidation window.
This finding was greeted with optimism for potential future applications in treating anxiety disorders, including PTSD. However, sweaty palms in anticipation of a mild shock is not exactly the same as the trauma of a disfiguring accident or a sexual assault.
Now, a group of Dutch researchers (Kroes et al., 2013) has taken a completely different approach to disrupt reconsolidaton in humans – namely, by reactivating recently learned memories in depressed patients immediately before administration of clinically prescribed electroconvulsive therapy (ECT).
ECT is sometimes used as a last resort in treating chronically depressed patients who've failed to respond to pharmaceutical and psychological therapies. Despite its floridly negative depiction in Hollywood movies, ECT is generally accepted within the psychiatric community as a highly effective treatment for intractable major depression (Kellner et al., 2012).1
The participants were 39 patients (mean age = 57 yrs) diagnosed primarily with moderate to severe recurrent major depressive disorder. They were either at the end of an acute treatment cycle or receiving maintenance ECT. The study used a between-subjects design with 3 different experimental conditions, with patients randomly assigned to Group A, B, or C (n=13 in each). The within-subjects factor was whether or not the patients received a reminder of previously learned material before treatment.
All participants learned two different emotionally charged slide stories with audio narration, each consisting of 11 images. In one, a boy is in an accident that severs his feet, which are reattached at the hospital. In the other, two sisters leave their home at night, and one is kidnapped at knife point and attacked by an escaped convict.
Memory for one of the stories was reactivated a week later by presenting part of the first slide, and then giving a test for this slide. The most surprising part comes next: only 4 minutes later (on average), Groups A and B were anesthetized and received ECT, which induced a seizure. Group C received their ECT treatment at a later date. The final memory test for Groups A and C was 24 hrs after the reminder, while Group B was tested as soon as they woke up from the procedure (mean = 104 min later). The final test consisted of 40 multiple choice questions about each of the stories.
Supplementary Fig. 1 (modified from Kroes et al. 2013). Study design. During the first study session, all groups were shown two emotional slide-show stories. During the second session, memory for one of the two stories was reactivated. Immediately after memory reactivation, patients in Groups A and B received ECT. For Group B, memory was tested immediately upon recovery from ECT (blue box). For Groups A and C, memory was tested one day after reactivation (red and orange respectively).
The basic idea here is that reconsolidation of the reactivated story isn't complete at 30 or 90 minutes, so Group B's test performance should be the same for the two stories. In contrast, reconsolidation is complete by 24 hrs, so for Group A the disruptive effect of ECT should selectively impair memory for the transiently reactivated story, which is in a labile state (relative to the "consolidated" story learned 7 days earlier).
And in fact, this is what the authors observed, as shown in the figure below. The horizontal dotted line depicts chance performance (25% accuracy) – no better than guessing. Group A performed at chance for the reactivated story, but remembered at least some of the non-reactivated story. In contrast, Group B performed significantly better than chance for both stories. Finally, Group C (the control group) remembered significantly more details about the reactivated story (relative to the non-reactivated story and compared to the other groups), since this served as a rehearsal opportunity that wasn't disrupted by ECT.
Fig. 1 (modified from Kroes et al. 2013). ECT disrupts reconsolidation. Memory scores on the multiple choice test are expressed as percentage correct (y axis). Memory for the reactivated story shown in solid bars and non-reactivated story in open bars. Each circle is the score for an individual patient. The horizontal dotted line is chance performance. Group A is in red, Group B in blue, and Group C in orange.
Although the number of patients in each group (and therefore the statistical power) weren't overwhelming, the study provides tentative evidence for the effectiveness of ECT in disrupting memories of the reconsolidated story. The potential import of this finding for future treatments is that the mere act of recalling highly unpleasant autobiographical memories immediately prior to ECT could assist in dampening future recall of these specific memories.
How practical is this idea? Would the ECT-induced amnesia be highly specific for the horrid memories, leaving pleasant ones intact? Read my companion post at The Neurocritic to find out.
1 An extensive review of the pros (e.g., effectiveness) and cons (e.g., memory loss) of ECT is beyond the scope of this post.
Alberini CM, Ledoux JE (2013). Memory reconsolidation. Curr Biol. 23:R746-50.
Kellner CH, Greenberg RM, Murrough JW, Bryson EO, Briggs MC, Pasculli RM. (2012). ECT in treatment-resistant depression. Am J Psychiatry 169:1238-44.
Kroes MC, Tendolkar I, van Wingen GA, van Waarde JA, Strange BA, & Fernández G (2013). An electroconvulsive therapy procedure impairs reconsolidation of episodic memories in humans. Nature neuroscience PMID: 24362759
Nader K, Hardt O. (2009). A single standard for memory: the case for reconsolidation. Nat Rev Neurosci. 10:224-34.
Schiller D, Monfils MH, Raio CM, Johnson DC, Ledoux JE, & Phelps EA (2010). Preventing the return of fear in humans using reconsolidation update mechanisms. Nature, 463 (7277), 49-53 PMID: 20010606