Periodic Reporting for period 1 - CLASSy Aging (Closed-Loop Acoustic Stimulation during Sleep to enhance motor memory consolidation in Aging)
Période du rapport: 2020-09-01 au 2022-08-31
According to the European Innovation Partnership dedicated to Active and Healthy Aging, the number of Europeans aged over 65 will double in the next 50 years, and the number of over 80-year-old will almost triple. Yet, unhealthy life years still represents approximately 20% of a person's life. As motor functioning is inextricably linked to the efficient performance of everyday life activities, it is thus of utmost importance, in our ageing society, to discover avenues to mitigate age-related deficits in motor learning.
Motor memory consolidation allows a newly acquired motor memory trace to be transformed into a more stable, robust form. Importantly, post-learning sleep is known to favour consolidation in young adults but to a lesser extent in elderly. This deficit has been partially attributed to age-related changes in the sleep characteristics, including slow waves (SW – high amplitude waves in the 0.5-4 Hz frequency band) and spindles (short burst in the sigma – 12-16 Hz – frequency band), two sleep-specific electrophysiological events involved in neuroplasticity. In recent years, there has been increasing evidence that consolidation processes can be augmented in young adults by experimental interventions such as targeted memory reactivation (TMR) applied during post-learning sleep. TMR consists of replaying offline (i.e. without further task practice) sensory stimuli that were associated to the task during learning and supposedly reactivate the memory trace. In this project, we tested whether targeted memory reactivation (TMR) can be used to enhance motor memory consolidation processes during post-learning sleep in young and older adults.
This research project had two specific goals: (1) to provide the behavioral correlates of TMR-induced modulation of motor memory consolidation and (2) to reveal the system-level neuroplasticity supporting the TMR-induced advantage (2.1) by identifying the direct effects of stimulation on the sleep-specific neuroplasticity events with electroencephalographic (EEG) recordings during sleep and (2.2) by assessing the changes in task-related brain patterns as quantified with pre- and post-sleep functional Magnetic Resonance Imaging (fMRI).
Motor memory consolidation allows a newly acquired motor memory trace to be transformed into a more stable, robust form. Importantly, post-learning sleep is known to favour consolidation in young adults but to a lesser extent in elderly. This deficit has been partially attributed to age-related changes in the sleep characteristics, including slow waves (SW – high amplitude waves in the 0.5-4 Hz frequency band) and spindles (short burst in the sigma – 12-16 Hz – frequency band), two sleep-specific electrophysiological events involved in neuroplasticity. In recent years, there has been increasing evidence that consolidation processes can be augmented in young adults by experimental interventions such as targeted memory reactivation (TMR) applied during post-learning sleep. TMR consists of replaying offline (i.e. without further task practice) sensory stimuli that were associated to the task during learning and supposedly reactivate the memory trace. In this project, we tested whether targeted memory reactivation (TMR) can be used to enhance motor memory consolidation processes during post-learning sleep in young and older adults.
This research project had two specific goals: (1) to provide the behavioral correlates of TMR-induced modulation of motor memory consolidation and (2) to reveal the system-level neuroplasticity supporting the TMR-induced advantage (2.1) by identifying the direct effects of stimulation on the sleep-specific neuroplasticity events with electroencephalographic (EEG) recordings during sleep and (2.2) by assessing the changes in task-related brain patterns as quantified with pre- and post-sleep functional Magnetic Resonance Imaging (fMRI).
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.
Results of this research program represent progress beyond the state of the art on two fronts. On a methodological level, the real-time EEG processing, combined with beyond state-of-the-art detection algorithms, allowed the sensory stimulation to be applied at specific phases of the slow oscillations associated with different levels of brain excitability. These methodological advances are very promising and open new perspectives for future fundamental research to direct (disrupt vs. enhance) the consolidation process. On a conceptual level, our research on SW stimulation revealed - for the first time – that acoustic stimulation during sleep can selectively impair memory. This conceptual advance is of the utmost importance especially for the treatment of disorders emerging from traumatic memories (such as PTSD). Moreover, the neuroimaging data collected in this project demonstrated the potential of sensory stimulation during sleep to indirectly modulate activity in deep brain regions critical for learning and memory. Finally, we raise awareness about the limited potential of TMR as a tool to boost motor memory consolidation processes in older adults. In sum, this project provided sound evidence to support the use of sensory stimulation during sleep to optimize memory in younger adults, an easy tool to transfer to clinical practice and eventually to wider society. Yet, we are calling for more efforts into tailoring stimulation approaches in order to minimize age-related motor deficits.