Causal role of prefrontal cortex in strengthening of episodic memories through reconsolidation

Abstract

Memory consolidation is a dynamic process. Reactivation of consolidated memories triggers reconsolidation, a time-limited period during which memories can be modified. Episodic memory refers to our ability to recall specific past events about what happened, including where and when. However, it is unknown whether noninvasive stimulation of the neocortex during reconsolidation might strengthen existing episodic memories in humans. To modify these memories, we applied repetitive transcranial magnetic stimulation (rTMS) over right lateral prefrontal cortex (PFC), a region involved in the reactivation of episodic memories. We report that rTMS of PFC after memory reactivation strengthened verbal episodic memories, an effect documented by improved recall 24 hr postreactivation compared to stimulation of PFC without reactivation and vertex (control site) after reactivation. In contrast, there was no effect of stimulation 1 hr postreactivation (control experiment), showing that memory strengthening is time dependent, consistent with the reconsolidation theory. Thus, we demonstrated that right lateral PFC plays a causal role in strengthening of episodic memories through reconsolidation in humans. Reconsolidation may serve as an opportunity to modify existing memories with noninvasive stimulation of a critical brain region, an issue of fundamental importance for memory research and clinical applications.

Figure 1

Timeline and results of experiment 1. Subjects learned 20 words on Day 1. On Day 2, rTMS was applied to right dorsolateral PFC (PFC-R) or a control site (Vertex-R) after memory reactivation by a spatial-contextual reminder. A third group of subjects received rTMS of right PFC without memory reactivation (PFC-NR). Recall was tested on Day 3. The plot shows the mean percentage of words recalled in each group (n=10). Error bars represent standard errors of the means (SEM). * p<0.0167. Cortical surfaces were generated using CARET (http://brainvis.wustl.edu/wiki/index.php/Main_Page).

Figure 2

Timeline and results of experiment 2. Subjects learned 20 words on Day 1. On Day 2, rTMS was applied to right dorsolateral PFC (PFC-R) or a control site (Vertex-R) after memory reactivation by a spatial-contextual reminder. Recall was tested shortly (30 min) after rTMS. The plot shows the mean percentage of words recalled in each group (n=10). Error bars represent standard errors of the means (SEM). Cortical surfaces were generated using CARET (http://brainvis.wustl.edu/wiki/index.php/Main_Page).