In order to address the goals mentioned above, we performed three experiments in which young and older healthy adults were trained on a motor sequence learning task that was reactivated (or not) using TMR during a post-learning sleep episode. The results of our first experiment confirmed the beneficial effect of TMR on motor performance in young adults. Importantly, they shed light on the neurophysiological processes supporting this enhancement. Specifically, we showed that, depending on their precise temporal coordination during post learning sleep, slow and sigma oscillations play a crucial role in either memory reinstatement or protection against irrelevant information; two processes that critically contribute to motor memory consolidation. In a follow-up experiment, we used a closed-loop stimulation paradigm that uses beyond the state-of-the-art online computing algorithms in order to deliver TMR at specific phases of the SW that are associated with different phases of brain excitability (high vs. low). Results in young adults showed that the reactivation of a memory trace at the high-excitability phase of the SW did not boost consolidation. In contrast, the low-excitability phase stimulation impaired motor memory consolidation. At the brain level, sleep EEG data indicated that the amplitude of the SW and the power in the sleep-specific sigma frequency band were lower during low-excitability stimulation as compared to high-excitability stimulation. Interestingly, the sigma band power during high-excitability stimulation correlated with motor performance improvements. Additionally, task-related MRI data analyses revealed phase-dependent modulations of brain activity in regions known for their critical role in motor memory consolidation (striatum and hippocampus). Importantly, these modulations were related to the TMR-related performance improvement. Last but not least, the results of our third experiment in elderly demonstrated that even though TMR induced modulation of sleep-related markers of plasticity in older adults, it did not improve motor performance. Altogether, our results do not only highlight the great potential of TMR to optimize memory consolidation in young adults but also shed light on the neurophysiological processes supporting this enhancement. However, our research does not indicate that TMR is an effective avenue to mitigate age-related deficits in motor memory consolidation. Future research is warranted to test the efficacy of interventions tailored to older individuals.
