Long term effects of cueing procedural memory reactivation during NREM sleep

Targeted memory reactivation (TMR) has recently emerged as a promising tool to manipulate and study the sleeping brain. Although the technique is developing rapidly, only a few studies have examined how the effects of TMR develop over time. Here, we use a bimanual serial reaction time task (SRTT) to investigate whether the difference between the cued and un-cued sequence of button presses persists long-term. We further explore the relationship between the TMR benefit and sleep spindles, as well as their coupling with slow oscillations. Our behavioural analysis shows better performance for the dominant hand. Importantly, there was a strong effect of TMR, with improved performance on the cued sequence after sleep. Closer examination revealed a significant benefit of TMR at 10 days post-encoding, but not 24 h or 6 weeks post-encoding. Time spent in stage 2, but not stage 3, of NREM sleep predicted cueing benefit. We also found a significant increase in spindle density and SO-spindle coupling during the cue period, when compared to the no-cue period. Together, our results demonstrate that TMR effects evolve over several weeks post-cueing, as well as emphasising the importance of stage 2, spindles and the SO-spindle coupling in procedural memory consolidation.