Anodal-tDCS exerts beneficial effects on cognition and brain functions in MCI, thereby providing a framework to test whether repeated stimulation sessions may yield sustained reversal of cognitive deficits.
It is hypothesized that deep sleep is essential for restoring the brain’s capacity to learn efficiently, especially in regions heavily activated during the day. However, causal evidence in humans has been lacking due to the inability to sleep deprive one target area while keeping the natural sleep pattern intact. Here we introduce a novel approach to focally perturb deep sleep in motor cortex, and investigate the consequences on behavioural and neurophysiological markers of neuroplasticity arising from dedicated motor practice. We show that the capacity to undergo neuroplastic changes is reduced by wakefulness but restored during unperturbed sleep. This restorative process is markedly attenuated when slow waves are selectively perturbed in motor cortex, demonstrating that deep sleep is a requirement for maintaining sustainable learning efficiency.
Study Objectives The restorative function of sleep has been linked to a net reduction in synaptic strength. The slope of slow-waves, a major characteristic of non-rapid eye movement (NREM) sleep, has been shown to directly reflect synaptic strength, when accounting for amplitude changes across the night. In this study, we aimed to investigate overnight slope changes in the course of development in an age-, amplitude-, and region-dependent manner. Methods All-night high-density electroencephalography data were analyzed in a cross-sectional population of 60 healthy participants in the age range of 8–29 years. To control for amplitude changes across the night, we matched slow-waves from the first and the last hour of NREM sleep according to their amplitude. Results We found a reduction of slow-wave slopes from the first to the last hour of NREM sleep across all investigated ages, amplitudes, and most brain regions. The overnight slope change was largest in children and decreased toward early adulthood. A topographical analysis revealed regional differences in slope change. Specifically, for small amplitude waves the decrease was smallest in an occipital area, whereas for large amplitude waves, the decrease was smallest in a central area. Conclusions The larger slope decrease in children might be indicative of a boosted renormalization of synapses during sleep in childhood, which, in turn, might be related to increased plasticity during brain maturation. Regional differences in the extent of slow-wave slope reduction may reflect a “smart” down-selection process or, alternatively, indicate amplitude-dependent differences in the generation of slow-waves.
Slow waves (1–4.5 Hz) are the most characteristic oscillations of deep non-rapid eye movement sleep. The EEG power in this frequency range (slow-wave activity, SWA) parallels changes in cortical connectivity (i.e., synaptic density) during development. In patients with attention-deficit/hyperactivity disorder (ADHD), prefrontal cortical development was shown to be delayed and global gray matter volumes to be smaller compared to healthy controls. Using data of all-night recordings assessed with high-density sleep EEG of 50 children and adolescents with ADHD (mean age: 12.2 years, range: 8–16 years, 13 female) and 86 age- and sex-matched healthy controls (mean age: 12.2 years, range: 8–16 years, 23 female), we investigated if ADHD patients differ in the level of SWA. Furthermore, we examined the effect of stimulant medication. ADHD patients showed a reduction in SWA across the whole brain (−20.5%) compared to healthy controls. A subgroup analysis revealed that this decrease was not significant in patients who were taking stimulant medication on a regular basis at the time of their participation in the study. Assuming that SWA directly reflects synaptic density, the present findings are in line with previous data of neuroimaging studies showing smaller gray matter volumes in ADHD patients and its normalization with stimulant medication.
Regional changes of non-rapid eye movement (NREM) sleep delta and sigma activity, and their temporal coupling have been related to experience-dependent plastic changes during previous wakefulness. These sleep-specific rhythms seem to be important for brain recovery and memory consolidation. Recently, it was demonstrated that by targeting slow waves in a particular region at a specific phase with closed-loop auditory stimulation, it is possible to locally manipulate slow-wave activity and interact with training-induced neuroplastic changes. In our study, we tested whether closed-loop auditory stimulation targeting the up-phase of slow waves might not only interact with the main sleep rhythms but also with their coupling within the circumscribed region. We demonstrate that while closed-loop auditory stimulation globally enhances delta, theta and sigma power, changes in cross-frequency coupling of these oscillations were more spatially restricted. Importantly, a significant increase in delta-sigma coupling was observed over the right parietal area, located directly posterior to the target electrode. These findings suggest that closed-loop auditory stimulation locally modulates coupling between delta phase and sigma power in a targeted region, which could be used to manipulate sleep-dependent neuroplasticity within the brain network of interest. A substantial body of evidence highlights the importance of non-rapid eye movement (NREM) sleep for experience-dependent neuroplasticity and associated improvements in behavioral performance after a bout of sleep 1,2. NREM sleep electroencephalographic (EEG) recordings are hallmarked by neocortical slow waves (1-4 Hz) and sleep spindles, the waxing and waning activity in the sigma frequency band (10-16 Hz). It is well established that slow waves orchestrate faster oscillations, with the up-phase of slow waves being associated with increased sigma band activity, and sigma oscillations, in turn, group gamma activity in their troughs 3,4. This precise crossfrequency phase-amplitude coupling is thought to organize communication across multiple brain areas and to facilitate coordinated information processing in brain networks during NREM sleep 5. Not only the magnitude and spatial distribution of slow waves and sigma activity 3,6-10 , but especially their temporal coupling seems to contribute to sleep-dependent benefits of behavioral performance 11,12. Similar to phase-amplitude coupling between slow waves and sigma, modulation of theta band activity (5-8 Hz) by the phase of slow waves has been described in several studies. Both in surface EEG and in intracranial (iEEG) recordings, theta power was increased during the transition to the down phase of slow waves, with the last trough of theta-burst coinciding with the slow-wave down-phase 5,13-15. Moreover, theta band activity in NREM sleep may play a role in sleep-dependent memory consolidation in humans. NREM theta oscillations were associated with the replay of the wake neuronal activity patterns during slow-wave sleep 16,17. Fur...
The glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is involved in synaptic plasticity processes, and animal studies have demonstrated altered expression across the sleep wake cycle. Accordingly, glutamate levels are reduced during non-rapid eye movement (NREM) sleep and the rate of this decrease is positively correlated with sleep EEG slow wave activity (SWA). Here, we combined proton magnetic resonance spectroscopy ( H-MRS) and high-density sleep EEG to assess if H-MRS is sensitive to diurnal changes of glutamate + glutamine (GLX) in healthy young adults and if potential overnight changes of GLX are correlated to SWA. H-MRS was measured in the parietal lobe in the evening and in the subsequent morning. High-density sleep EEG was recorded overnight between the evening and morning scans. Our results revealed a significant overnight reduction in GLX, but no significant changes in other metabolites. The decrease in GLX positively correlated with the decrease of SWA. Our study demonstrates that quantification of diurnal changes in GLX is possible by means of H-MRS and indicates that overnight changes in GLX are related to SWA, a marker that is closely linked to the restorative function of sleep. This relationship might be of particular interest in clinical populations in which sleep is disturbed.
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