Cued reactivation of motor learning during sleep leads to overnight changes in functional brain activity and connectivity

Sleep plays a role in memory consolidation. This is demonstrated by improved performance and neural plasticity underlying that improvement after sleep. Targeted memory reactivation (TMR) allows the manipulation of sleep-dependent consolidation through intentionally biasing the replay of specific memories in sleep, but the underlying neural basis of these altered memories remains unclear. We use functional magnetic resonance imaging (fMRI) to show a change in the neural representation of a motor memory after targeted reactivation in slow-wave sleep (SWS). Participants learned two serial reaction time task (SRTT) sequences associated with different auditory tones (high or low pitch). During subsequent SWS, one sequence was reactivated by replaying the associated tones. Participants were retested on both sequences the following day during fMRI. As predicted, they showed faster reaction times for the cued sequence after targeted memory reactivation. Furthermore, increased activity in bilateral caudate nucleus and hippocampus for the cued relative to uncued sequence was associated with time in SWS, while increased cerebellar and cortical motor activity was related to time in rapid eye movement (REM) sleep. Functional connectivity between the caudate nucleus and hippocampus was also increased after targeted memory reactivation. These findings suggest that the offline performance gains associated with memory reactivation are supported by altered functional activity in key cognitive and motor networks, and that this consolidation is differentially mediated by both REM sleep and SWS