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- Resumen es exacto "The last decade has seen remarkable advances in the identification of neural markers of sleep-dependent memory consolidation. However, most advances have emerged from the field of declarative memory, possibly because of the vast evidence suggesting that only hippocampal-dependent learning benefits from sleep. Sleep-dependent reactivation of hippocampal memories appears to depend on the precise synchrony between slow oscillations (SO) and sleep spindles, a mechanism framed by the systems consolidation hypothesis. In the present thesis, we sought to examine the role of sleep in the consolidation of motor memories in humans, and to identify neural markers associated with the consolidation process. Given that the role of sleep in motor adaptation is somewhat controversial, in two initial experiments we tested the hypothesis that sleep plays a role in the consolidation of motor adaptation memories (MA) by manipulating the temporal proximity between learning and sleep (PLS), such that in each experiment one group had the opportunity to initiate sleep ~10 minutes after learning (PLS-10min) and the other group did so ~14 hours later (PLS-14hs). In Experiment 1, volunteers performed a MA session to a single perturbation, and in Experiment 2 they performed an anterograde interference protocol by facing two opposite perturbations separated by a 5-min interval. We found that the temporal proximity between training and sleep increased memory retention by 30%, a phenomenon that persisted for at least two weeks, suggesting that this type of learning benefits from sleep when it occurs during the consolidation window. However, a protective effect of sleep against interference was not observed. Next, with the aim of identifying neural markers that support sleep-dependent stabilization of MA memories, we conducted another study (Experiment 3) in which a new group of volunteers was exposed to a MA session and a control session (CTL) following the PLS-10min protocol. We found that MA increased the global density of fast (≥12 Hz) but not slow (<12Hz) sleep spindles during NREM3. This modulation was manifested locally, over the hemisphere contralateral to the trained hand. Motor learning also increased the proportion of spindles clustered in trains (inter-spindle intervals ≤ 6 seconds), a phenomenon that has recently been linked to memory reactivation. This effect was observed only during NREM3, also locally, over the hemisphere contralateral to the trained hand. Moreover, this interhemispheric modulation was significantly correlated with long-term memory retention. To explore the potential relevance of spindle clustering on sleep-dependent plasticity, we quantified the impact of MA on spindle duration and spindle amplitude. We found that both intrinsic features increased as a function of train length, and reached higher values than isolated spindles. We also found that spindle duration and amplitude increased in magnitude as a function of train length, with the latter spindles of a train being longer and of greater amplitude than the former. These findings are consistent with a role for spindles in memory reactivation and neural plasticity. Moreover, although adaptive learning did not affect OL density, it increased delta-band (1-4 Hz) power locally, interhemispherically, during the first 30 min compared to the last 30 min of NREM sleep, in line with the hypothesis of synaptic homeostasis (SHY) as a potential mechanism mediating the stabilization of memories during sleep. Finally, we observed that MA substantially increased the number of fast spindles coupled to the active phase of SO (around their positive peak). The fact that only SO-coupled spindles (and not uncoupled spindles) predicted memory retention after sleep points to the relevance of this association in motor memory consolidation. Finally, to assess whether the PLS manipulation also impacts spindle-SO coupling and delta activity, EEG recordings from both groups of Experiment 1 were studied in which a benefit of sleep proximity on long-term memory retention was observed. In the PLS-10min group, a modulation in the density of fast spindles was detected during NREM sleep (stages 2 and 3), showing an increase in this measure in the hemisphere contralateral to the trained hand, with respect to the ipsilateral one. In addition, the coupling between fast spindles and SO also underwent interhemispheric modulation. In the same vein, delta power was also modulated interhemispherically at the onset of NREM sleep. Notably, these measures were modulated only in the PLS-10min group, in which sleep occurred within the MA memory consolidation window, and not in the PLS-14hs. Taken together, these results provide evidence in favor of common mechanisms in the stabilization of declarative and procedural memories."
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