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Abstract

Sleep-related consolidation of declarative memories, as well as associated neurophysiological events such as slow oscillatory and spindle activity, deteriorate in the course of aging. This process is accelerated in neurodegenerative disease. Transcranial slow oscillatory stimulation (so-tDCS) during sleep has been shown to enhance slow oscillatory brain activity and thereby improve memory consolidation in young subjects. Here, we investigated whether so-tDCS applied to older adults during an afternoon nap exerts similar effects.

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... Slow-wave oscillations increase after a learning episode (Molle et al. 2004) and with time awake, whereas they decrease during sleep as the night progresses (Tononi and Cirelli 2014). Boosting their amplitude and duration during sleep by means of non-invasive brain stimulation results in better encoding of information and increased memory retention (Marshall et al. 2006;Antonenko et al. 2013;Ladenbauer et al. 2016Ladenbauer et al. , 2017, whereas disrupting them impairs the restorative property of sleep (Aeschbach et al. 2008;Fattinger et al. 2017, although see Paßmann et al. 2016). Interestingly, a causal link between slow-wave oscillations and learning is further suggested by the finding that these oscillations may be entrained in the awake human brain and that such entrainment can enhance encoding processes (Kirov et al. 2009). ...
... While there is no consensus regarding the mechanisms of action of tACS, recent literature has focussed on detecting local, long-lasting increases in oscillatory power at the stimulation frequency, which could be explained in terms of entrainment of cortical oscillatory activity (Ozen et al. 2010;Ali et al. 2013;Helfrich et al. 2014;Alagapan et al. 2016, although see Vossen et al. 2015 for a network plasticity account). More specifically, with regard to slow oscillations, a number of studies using scalp EEG recordings in humans have reported locally increased power in the low-frequency band immediately following slow-oscillatory tDCS to frontal cortex (Marshall et al. 2006;Kirov et al. 2009;Antonenko et al. 2013;Westerberg et al. 2015;Paßmann et al. 2016;Ladenbauer et al. 2016Ladenbauer et al. , 2017. In contrast, the current study found no evidence for a specific power increase in the lowfrequency band immediately following active tACS. ...
... This apparent discrepancy with previous studies is likely attributable to several factors. First, all but one previous study delivered slow-oscillatory tDCS during sleep-either a nap or a full-night's sleep (Marshall et al. 2006;Antonenko et al. 2013;Westerberg et al. 2015;Paßmann et al. 2016;Ladenbauer et al. 2016Ladenbauer et al. , 2017, when cortical slow oscillations are expected to occur endogenously (Steriade et al. 1993). It is possible that to achieve modulation of slow oscillations via tACS, the network needs to be in a state that enables generation of slow oscillations, or that such oscillations need to be present at the time of stimulation. ...
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Article
Previous history of activity and learning modulates synaptic plasticity and can lead to saturation of synaptic connections. According to the synaptic homeostasis hypothesis, neural oscillations during slow-wave sleep play an important role in restoring plasticity within a functional range. However, it is not known whether slow-wave oscillations-without the concomitant requirement of sleep-play a causal role in human synaptic homeostasis. Here, we aimed to answer this question using transcranial alternating current stimulation (tACS) to induce slow-oscillatory activity in awake human participants. tACS was interleaved between two plasticity-inducing interventions: motor learning, and paired associative stimulation (PAS). The hypothesis tested was that slow-oscillatory tACS would prevent homeostatic interference between motor learning and PAS, and facilitate plasticity from these successive interventions. Thirty-six participants received sham and active fronto-motor tACS in two separate sessions, along with electroencephalography (EEG) recordings, while a further 38 participants received tACS through a control montage. Motor evoked potentials (MEPs) were recorded throughout the session to quantify plasticity changes after the different interventions, and the data were analysed with Bayesian statistics. As expected, there was converging evidence that motor training led to excitatory plasticity. Importantly, we found moderate evidence against an effect of active tACS in restoring PAS plasticity, and no evidence of lasting entrainment of slow oscillations in the EEG. This suggests that, under the conditions tested here, slow-oscillatory tACS does not modulate synaptic homeostasis in the motor system of awake humans.
... Application of oscillatory protocols with frequency <1 Hz (slow oscillatory transcranial direct current stimulation, so-tDCS) during NREM sleep provides a non-invasive method of manipulating cortical SO activity [7][8][9][10], and improves the precisely timed coupling between endogenous SOs and spindles, as shown in patients with mild cognitive impairment [8]. Critically, in parallel, so-tDCS improves memory retention performance at group level [7][8][9][10][11], with coupling between SO and spindles being most informative for memory retention performance [8]. ...
... Application of oscillatory protocols with frequency <1 Hz (slow oscillatory transcranial direct current stimulation, so-tDCS) during NREM sleep provides a non-invasive method of manipulating cortical SO activity [7][8][9][10], and improves the precisely timed coupling between endogenous SOs and spindles, as shown in patients with mild cognitive impairment [8]. Critically, in parallel, so-tDCS improves memory retention performance at group level [7][8][9][10][11], with coupling between SO and spindles being most informative for memory retention performance [8]. Therefore, so-tDCS during sleep not only represents a non-invasive, welltolerated method to test causal effects of external SO induction on endogenous oscillatory rhythms and its relation to memory, but may also provide a promising treatment method in aging individuals with memory decline in the future. ...
... However, response to stimulation on electrophysiological and behavioral levels varied quite markedly between individuals [8][9][10], studies [9,10,12,13] and species [14,15]. Some studies did not find an overall effect [13,16]. ...
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Preprint
Background: Oscillatory rhythms during sleep such as slow oscillations (SO) and spindles, and most importantly their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation, however, effects varied quite markedly between individuals, studies and species. Objective: Here, we aimed to determine how precisely the frequency of stimulation has to match the naturally occurring SO frequency in individuals to optimally improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes. Methods: We addressed these questions by comparing so-tDCS with individually adapted SO frequency to standardized frequency of 0.75Hz in a cross-over design with 28 healthy older participants during napping while systematically varying stimulation train durations between 30s, 2min and 5min. Results: Stimulation trains as short as 30s were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects with regard to SO-spindle coupling in comparison to individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated. Conclusion: Short stimulation trains were sufficient to induce significant changes in sleep physiology allowing for more trains of stimulation, which provides methodological advantages and possibly even larger effects in future studies. With regard to individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation to calibrate stimulation frequency to the SO frequency at time of stimulation onset.
... Interestingly, the so-tDCS intervention showed positive effects on memory in healthy elderly and MCI patients when applied during a daytime nap [26][27][28] , but not during nocturnal sleep 29,30 . Daytime napping is strongly pronounced in older adults 31 and even more frequent in older people at risk of dementia 32 , possibly to compensate for poorer sleep quality during nocturnal sleep. ...
... Daytime napping is strongly pronounced in older adults 31 and even more frequent in older people at risk of dementia 32 , possibly to compensate for poorer sleep quality during nocturnal sleep. The interventional studies mentioned above have demonstrated improvements on the physiological and functional scale during napping [26][27][28] , suggesting that napping may not only constitute a useful model for sleep physiology in general, but also a convenient target for sleeprelated interventions. However, little is known about sleep characteristics during napping, and how they change in older adults with and without MCI. ...
... Data from a subset of participants has been reported previously. 26,28 Eligible participants underwent a structured telephone interview to clarify major exclusion criteria, including history of severe untreated medical, neurological, and psychiatric diseases; sleep disorders; intake of antidepressants; alcohol or substance abuse; and non-fluent German language abilities. MCI patients (amnestic; single and multiple domain) were diagnosed according to Mayo criteria based on subjective cognitive complaints and objective memory impairment in standardized tests, relatively preserved general cognition, no impairment in activities of daily living, and no dementia 33 . ...
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Study Objectives Aging is associated with detrimental changes in sleep physiology, a process accelerated in Alzheimer's disease (AD). Fine-tuned temporal interactions of NREM slow oscillations (SO) and spindles were shown to be particularly important for memory consolidation, and to deteriorate in healthy older adults. Whether this oscillatory interaction further declines in early stages of AD such as mild cognitive impairment (MCI) has not been investigated to date, but may have important therapeutic implications. Methods Here, we assessed differences in sleep architecture and memory-relevant SO, sleep spindles and their functional coupling during a 90-min nap between healthy young and older adults, and in older patients with MCI. Furthermore, associations of nap-sleep characteristics with sleep-dependent memory performance change were evaluated. Results We found significant differences between young and older healthy adults, and between young adults and patients with MCI, but not between healthy older adults and patients for several sleep metrics, including SO-spindle coupling. Moreover, sleep-dependent retention of verbal memories was significantly higher in young healthy adults versus older adults with and without MCI, but no difference between the two older groups was observed. Associations with sleep metrics were only found for pre-nap memory performances. Conclusions In conclusion, our results indicate changes in nap sleep physiology and sleep-related memory consolidation in older adults with and without MCI. Thus, interventions targeted at improving sleep physiology may help to reduce memory decline in both groups, but our study does not indicate additional benefits for patients with MCI.
... Three sotDCS studies however reported no significant improvement in associative memory (54,57,61). Whilst these used similar memory tasks to Westerberg et al. (63), they differed in stimulation location by applying stimulation bilaterally to the frontal lobes but with electrodes placed in areas F3 and F4 (international 10-20 EEG system). ...
... Eggert et al. (54) found that sotDCS during early non-REM sleep did not improve wordpair memory consolidation, and that across conditions memory generally deteriorated following sleep. Ladenbauer et al. (57) and Paßmann et al. (61) both found that participants recalling lists of word-pairs or object-location pairings generally performed worse following a nap, with no significant differences between sham and sotDCS. ...
... Two further paradigms explored the effects of non-invasive brain stimulation on episodic memory using sotDCS (57,61), of which both found significant effects. Ladenbauer et al. (57), during the previously cited visuo-spatial associative memory task, found that bilateral F3 and F4 stimulation during a nap significantly improved recognition memory of visual scenes presented prior to falling asleep (as compared to no stimulation). ...
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Article
It has long been acknowledged that memory changes over the course of one's life, irrespective of diseases like dementia. Approaches to mitigate these changes have however yielded mixed results. Brain stimulation has been identified as one novel approach of augmenting older adult's memory. Thus far, such approaches have however been nuanced, targeting different memory domains with different methodologies. This has produced an amalgam of research with an unclear image overall. This systematic review therefore aims to clarify this landscape, evaluating, and interpreting available research findings in a coherent manner. A systematic search of relevant literature was conducted across Medline, PsycInfo, Psycarticles and the Psychology and Behavioral Sciences Collection, which uncovered 44 studies employing non-invasive electrical brain stimulation in healthy older adults. All studies were of generally good quality spanning numerous memory domains. Within these, evidence was found for non-invasive brain stimulation augmenting working, episodic, associative, semantic, and procedural memory, with the first three domains having the greatest evidence base. Key sites for stimulation included the left dorsolateral prefrontal cortex (DLPFC), temporoparietal region, and primary motor cortex, with transcranial direct current stimulation (tDCS) holding the greatest literature base. Inconsistencies within the literature are highlighted and interpreted, however this discussion was constrained by potential confounding variables within the literature, a risk of bias, and challenges defining research aims and results. Non-invasive brain stimulation often did however have a positive and predictable impact on older adult's memory, and thus warrants further research to better understand these effects.
... The memory tasks consisted of two declarative memory tests (a word-pairs task [20] and a visuo-spatial task including picture and location memory [21]) (Fig. 2). All memory tasks were implemented with Psychtoolbox (http://psychtoolbox.org). ...
... To compare the EEG feature in the spectral and spatial domain, we grouped into five brain regions as follows: frontal, central, temporal, parietal, and occipital regions. In addition, we divided into six frequency bands as follows: delta (0.5-4 Hz), theta (4-7 Hz), alpha (7-12 Hz), spindle (12-16 Hz), beta (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (30-50 Hz) bands. ...
... On the other hand, picture memory has been demonstrated to be less dependent on memory consolidation as in the previous studies [32]. Finally, the reduction in the performance of location memory may be due to the combination of simple picture memory task and more complex location memory task, resulting in fewer valid items [21]. ...
Preprint
The assessment of consciousness and unconsciousness is a challenging issue in modern neuroscience. Consciousness is closely related to memory consolidation in that memory is a critical component of conscious experience. So far, many studies have been reported on memory consolidation during consciousness, but there is little research on memory consolidation during unconsciousness. Therefore, we aim to assess the unconsciousness in terms of memory consolidation using electroencephalogram signals. In particular, we used unconscious state during a nap; because sleep is the only state in which consciousness disappears under normal physiological conditions. Seven participants performed two memory tasks (word-pairs and visuo-spatial) before and after the nap to assess the memory consolidation during unconsciousness. As a result, spindle power in central, parietal, occipital regions during unconsciousness was positively correlated with the performance of location memory. With the memory performance, there was also a negative correlation between delta connectivity and word-pairs memory, alpha connectivity and location memory, and spindle connectivity and word-pairs memory. We additionally observed the significant relationship between unconsciousness and brain changes during memory recall before and after the nap. These findings could help present new insights into the assessment of unconsciousness by exploring the relationship with memory consolidation.
... Based on the positive outcomes of the last years, the attention has recently shifted to the elderly population, which represents an attractive target due to the typical sleep alterations characterizing the aging process. To date, five studies [26,[56][57][58][59] tested the efficacy of so-tDCS in older adults, assessing both the electrophysiological and cognitive domains (Table 1). Of note, the majority of studies have replicated the protocol of Marshall and colleagues [51], but the variations of timing or other parameters of the stimulation will be discussed in detail below. ...
... Ladenbauer and colleagues [57] replicated the application of so-tDCS on the elderly population (18 subjects; mean age, 65 years) during a 90-minute nap, complementing the procedural (SFTT) and declarative (WPAT) memory assessment with a visuo-spatial task implying both visual and location memory. Differently to Marshall and colleagues [51], the 1-minute stimulation-free intervals were prolonged of further 40 seconds, which were not considered in the subsequent analyses, due to the long-lasting artifacts following stimulation. ...
... At the electrophysiological level, so-tDCS led to an increment in SO and fast spindle frequency bands, as well as in fast spindle density. In light of these results, Ladenbauer and colleagues [57] confirmed the possibility to effectively modulate sleep physiology boosting declarative memory consolidation, although also in this case the sleep modifications were not directly correlated to memory consolidation improvement. ...
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Article
Sleep represents a crucial time window for the consolidation of memory traces. In this view, some brain rhythms play a pivotal role, first of all the sleep slow waves. In particular, the neocortical slow oscillations (SOs), in coordination with the hippocampal ripples and the thalamocortical spindles, support the long-term storage of the declarative memories. The aging brain is characterized by a disruption of this complex system with outcomes on the related cognitive functions. In recent years, the advancement of the comprehension of the sleep-dependent memory consolidation mechanisms has encouraged the development of techniques of SO enhancement during sleep to induce cognitive benefits. In this review, we focused on the studies reporting on the application of acoustic or electric stimulation procedures in order to improve sleep-dependent memory consolidation in older subjects. Although the current literature is limited and presents inconsistencies, there is promising evidence supporting the perspective to non-invasively manipulate the sleeping brain electrophysiology to improve cognition in the elderly, also shedding light on the mechanisms underlying the sleep-memory relations during healthy and pathological aging.
... More recently, Cona et al. (2014) proposed a new NMM to describe a "sleeping" thalamocortical system with tonic and bursting firing modes within thalamic neurons while Schellenberger Costa et al. (2016) probed a thalamocortical model that generates spindles and K-complexes. To this date, however, no study focused on the cross-frequency slow oscillation-spindle interaction in the model setting that would mimic the empirical findings (Ladenbauer et al., 2016Helfrich et al., 2018). We aim to close this gap in the present study. ...
... only. In this setting, this motif well reproduces the SO-correlated spindling observed during NREM sleep Ladenbauer et al., 2016Ladenbauer et al., , 2017Helfrich et al., 2018). Changing the conductance g h of TCR's rectifying current, the ratio between the numbers of "free" and SO-correlated spindle events can be adapted. ...
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Article
Sleep manifests itself by the spontaneous emergence of characteristic oscillatory rhythms, which often time-lock and are implicated in memory formation. Here, we analyze a neural mass model of the thalamocortical loop in which the cortical node can generate slow oscillations (approximately 1 Hz) while its thalamic component can generate fast sleep spindles of σ-band activity (12–15 Hz). We study the dynamics for different coupling strengths between the thalamic and cortical nodes, for different conductance values of the thalamic node's potassium leak and hyperpolarization-activated cation-nonselective currents, and for different parameter regimes of the cortical node. The latter are listed as follows: (1) a low activity (DOWN) state with noise-induced, transient excursions into a high activity (UP) state, (2) an adaptation induced slow oscillation limit cycle with alternating UP and DOWN states, and (3) a high activity (UP) state with noise-induced, transient excursions into the low activity (DOWN) state. During UP states, thalamic spindling is abolished or reduced. During DOWN states, the thalamic node generates sleep spindles, which in turn can cause DOWN to UP transitions in the cortical node. Consequently, this leads to spindle-induced UP state transitions in parameter regime (1), thalamic spindles induced in some but not all DOWN states in regime (2), and thalamic spindles following UP to DOWN transitions in regime (3). The spindle-induced σ-band activity in the cortical node, however, is typically the strongest during the UP state, which follows a DOWN state “window of opportunity” for spindling. When the cortical node is parametrized in regime (3), the model well explains the interactions between slow oscillations and sleep spindles observed experimentally during Non-Rapid Eye Movement sleep. The model is computationally efficient and can be integrated into large-scale modeling frameworks to study spatial aspects like sleep wave propagation.
... The three naps were separated by ~ 5-6 weeks (mean ± SD time between T1 and T2: 31.2 ± 41.1 days; mean ± SD time between T2 and T3: 45.2 ± 32.1 days). A comprehensive neuropsychological testing was administered for assessment of cognitive status in each participant (Ladenbauer et al., 2016;Ladenbauer et al., 2017). Here, we used the verbal learning and memory test to probe memory performance (see below), which was acquired prior sleep on T1. ...
... Only naps with a minimum duration of sleep stages 2, 3, and 4 of 15 min were included in the analysis, resulting in the following number of excluded naps: 3 in T1, 2 in T2, and 1 in T3. To characterize the temporal relationship between SOs and spindles, as well as delta waves and spindles, we performed time-frequency representations (TFR) and phase-amplitude coupling (PAC) analysis for frontal (Fz, FC1, FC2) and centroparietal (Cz, CP1, CP2) region-of-interests (ROI) (Ladenbauer et al., 2016;Ladenbauer et al., 2017). These were calculated on 30-s non-overlapping epochs of NREM sleep stage 2, 3 and 4 (sampling rate 500 Hz). ...
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Certain neurophysiological characteristics of sleep, in particular slow oscillations (SO), sleep spindles, and their temporal coupling, have been well characterized and associated with human memory formation. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SO, have only recently been found to play a critical role in memory processing of rodents, through a competitive interplay between SO-spindle and delta-spindle coupling. However, human studies that comprehensively address delta waves, their interactions with spindles and SOs as well as their functional role for memory are still lacking. Electroencephalographic data were acquired across three naps of 33 healthy older human participants (17 female) to investigate delta-spindle coupling and the interplay between delta and SO-related activity. Additionally, we determined intra-individual stability of coupling measures and their potential link to the ability to form novel memories. Our results revealed weaker delta-spindle compared to SO-spindle coupling. Contrary to our initial hypothesis, we found that increased delta activity was accompanied by stronger SO-spindle coupling. Moreover, we identified the ratio between SO- and delta-nested spindles as the sleep parameter that predicted ability to form novel memories best. Our study suggests that SOs, delta waves and sleep spindles should be jointly considered when aiming to link sleep physiology and memory formation in aging. Significance statement Interrelations between delta waves, slow oscillations and sleep spindles have recently been causally linked to the balance between consolidation and forgetting in rats using optogenetics. In humans, SO-spindle coupling has been intensively investigated, but delta waves and their interaction with spindles were only studied jointly as SWA. Here we delineate the coupling of delta waves to spindles, investigate interactions of delta- and SO-related activity and investigate their role for the ability to form novel memories in healthy older individuals. Our results show differences as well as dependencies between SO- and delta-related activities including spindle coupling. Further, our results indicate that the ratio of SO- to delta-nested spindles might be the most informative sleep parameter for memory formation of older adults.
... [27] probed a thalamocortical model that generates spindles and K-complexes. To this date, however, no study focused on the cross-frequency slow oscillationspindle interaction in the model setting that would mimic the empirical findings [33,34,35]. We aim to close this gap with the present study. ...
... With few exceptions, thalamic spindles are induced right after cortical UP to DOWN transitions, but -given the short duration of the cortical DOWN state -every SO induces one thalamic spindle only. In this setting, this motif well reproduces the SO-correlated spindling observed during NREM sleep [15,33,34,35]. Changing the conductance g h of TCR's rectifying current, the ratio between the numbers of "free" and SO-correlated spindle events can be adapted. ...
Full-text available
Preprint
Sleep manifests itself by the spontaneous emergence of characteristic oscillatory rhythms, which often time-lock and are implicated in the memory formation. Here, we analyze a neural mass model of the thalamo-cortical loop of which the cortical node can generate slow oscillations (approx. 1 Hz) while its thalamic component can generate sleep spindles of σ-band activity (12-15 Hz). We study the dynamics for different coupling strengths between the thalamic and cortical nodes, for different conductance values of the thalamic node's potassium leak and anomalous rectifying currents, and for different parameter regimes of the cortical node. The latter are: (1) a low activity (DOWN) state with noise-induced, transient excursions into a high activity (UP) state, (2) an adaptation induced slow oscillation limit cycle with alternating UP and DOWN states, and (3) a high activity (UP) state with noise-induced, transient excursions into the low activity (DOWN) state. During UP states, thalamic spindling is abolished or reduced. During DOWN states, the thalamic node generates sleep spindles, which in turn can cause DOWN to UP transitions in the cortical node. Consequently, this leads to spindle-induced UP state transitions in parameter regime (1), thalamic spindles induced in some but not all DOWN states in regime (2), and thalamic spindles following UP to DOWN transitions in regime (3). The spindle-induced σ-band activity in the cortical node, however, is typically strongest during the UP state, which follows a DOWN state "window of opportunity" for spindling. When the cortical node is parametrized in regime (3), the model well explains the interactions between slow oscillations and sleep spindles observed experimentally during Non-Rapid Eye Movement sleep. The model is computationally efficient and can be integrated into large-scale modeling frameworks to study spatial aspects like sleep wave propagation.
... Partially consistent results have been found by Ladenbauer and coworkers [194]. Indeed, so-tDCS during a nap improved picture memory retention and increased frontal SO activity and fast spindle activity in older adults compared to a sham protocol, without changes in sleep architecture and spatial and verbal memory. ...
... Only one study assessed the effect of so-tDCS compared to sham during a daytime nap in subjects with aMCI [196]. Consistently with the administration of an identical protocol in healthy elderly [194], the stimulation induced an improvement in visual declarative memory but not in spatial and verbal memory. Considering the EEG measures, so-tDCS provoked an increase in SO and spindle power and enhanced SO-fast spindles power coupling. ...
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Article
The multifactorial nature of Alzheimer’s disease (AD) has led scientific researchers to focus on the modifiable and treatable risk factors of AD. Sleep fits into this context, given the bidirectional relationship with AD confirmed by several studies over the last years. Sleep disorders appear at an early stage of AD and continue throughout the entire course of the pathology. Specifically, sleep abnormalities, such as more fragmented sleep, increase in time of awakenings, worsening of sleep quality and primary sleep disorders raise with the severity and progression of AD. Intervening on sleep, therefore, means acting both with prevention strategies in the pre-clinical phase and with treatments during the course of the disease. This review explores sleep disturbances in the different stages of AD, starting from the pre-clinical stage. Particular attention is given to the empirical evidence investigating obstructive sleep apnea (OSA) disorder and the mechanisms overlapping and sharing with AD. Next, we discuss sleep-based intervention strategies in the healthy elderly population, mild cognitive impairment (MCI) and AD patients. We mention interventions related to behavioral strategies, combination therapies, and bright light therapy, leaving extensive space for new and raising evidence on continuous positive air pressure (CPAP) treatment effectiveness. Finally, we clarify the role of NREM sleep across the AD trajectory and consider the most recent studies based on the promising results of NREM sleep enhancement, which use innovative experimental designs and techniques.
... The visuo-spatial memory task consisted of picture and location memory [16]) and was implemented using Psychtoolbox (http://psychtoolbox.org). All participants were asked to encode a set of 38 images (objects, plants, and scenes taken from the SUN database [17]) (picture memory) and where the images were presented (location memory). ...
... To analyze the frequency domain of the prepossessed EEG signals, we calculated the power spectral density (PSD) using a fast Fourier transform (FFT) [19]. We divided into 6 frequency bands as follows: delta (0.5-4 Hz), theta (4-7 Hz), alpha (7-12 Hz), spindle (12)(13)(14)(15), beta (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (30-50 Hz) bands. PSD was obtained for each frequency component composing those EEG signals [20]- [22]: ...
Preprint
Memory is an essential element in people's daily life based on experience. So far, many studies have analyzed electroencephalogram (EEG) signals at encoding to predict later remembered items, but few studies have predicted long-term memory only with EEG signals of successful short-term memory. Therefore, we aim to predict long-term memory using deep neural networks. In specific, the spectral power of the EEG signals of remembered items in short-term memory was calculated and inputted to the multilayer perceptron (MLP) and convolutional neural network (CNN) classifiers to predict long-term memory. Seventeen participants performed visuo-spatial memory task consisting of picture and location memory in the order of encoding, immediate retrieval (short-term memory), and delayed retrieval (long-term memory). We applied leave-one-subject-out cross-validation to evaluate the predictive models. As a result, the picture memory showed the highest kappa-value of 0.19 on CNN, and location memory showed the highest kappa-value of 0.32 in MLP. These results showed that long-term memory can be predicted with measured EEG signals during short-term memory, which improves learning efficiency and helps people with memory and cognitive impairments.
... In healthy older adults, three studies have reported the enhancement of sleep SOs following tDCS application during a nap (Westerberg et al., 2015;Ladenbauer et al., 2016;Paßmann et al., 2016); in two of them (Westerberg et al., 2015;Ladenbauer et al., 2016), the improvement in sleep-mediated declarative memory was also present. These positive findings contrast with those from a previous study conducted during nighttime sleep (Eggert et al., 2013) in which tDCS did not enhance SOs and actually worsened both declarative and non-declarative sleep-dependent memory, possibly related to the disruption and reduction in SWS duration. ...
... In healthy older adults, three studies have reported the enhancement of sleep SOs following tDCS application during a nap (Westerberg et al., 2015;Ladenbauer et al., 2016;Paßmann et al., 2016); in two of them (Westerberg et al., 2015;Ladenbauer et al., 2016), the improvement in sleep-mediated declarative memory was also present. These positive findings contrast with those from a previous study conducted during nighttime sleep (Eggert et al., 2013) in which tDCS did not enhance SOs and actually worsened both declarative and non-declarative sleep-dependent memory, possibly related to the disruption and reduction in SWS duration. ...
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Article
Sleep plays a critical role in the process of memory consolidation. In particular, during non-rapid eye movement (NREM) slow wave sleep, slow-oscillations, spindles, hippocampal sharp wave ripples, and their phase coupling, are involved in the process of transferring and consolidating information recently encoded and temporarily stored in the hippocampus into long-term memory stored in the neocortex. There is evidence that aging and neurodegenerative conditions, in particular Alzheimer's disease, are associated with changes to this transient grouping of NREM oscillations. Therefore, methods to enhance sleep, particularly slow wave sleep, have the potential to improve cognitive performance. Transcranial electrical and magnetic stimulation have been shown useful to enhance sleep slow-waves and sleep-dependent memory consolidation, however there is need for more information regarding proper protocols of application, and applicability and efficacy in patients with neurodegenerative conditions. Acoustic stimulation during sleep has been proven particularly effective in enhancing sleep slow-waves and spindles with associated improvement in overnight memory consolidation. More importantly, preliminary data indicate that similar results can be achieved in healthy older adults and those with amnestic mild cognitive impairment. Studies are needed to optimize the modalities of acoustic stimulation during sleep, which may vary based on age group or clinical disorder. Overall, non-invasive techniques of neurostimulation may represent a valid approach to mitigate cognitive decline associated with aging and neurodegeneration. Furthermore, they offer the unique opportunity to improve our understanding of the physiology behind sleep-dependent memory consolidation.
... A corrente alternada é outra forma de estimulação transcraniana relevante, porque é uma alternativa possível no tratamento de doenças neuropsiquiátricas que apresentam oscilações cerebrais alteradas, como é o caso do TDAH. Estudos evidenciaram efetividade na alteração da percepção, cognição e de oscilações nesses pacientes (FEURRA et al., 2011;LADENBAUER et al., 2016;ANTONENKO et al., 2016;KASTEN & HERRMANN, 2017;BUMKE, C. & VOßKUHLE, 2015;RUHNAU et al., 2016;BEUTNER, E. & ZÄHLE, 2010). ...
Chapter
A Neurologia é a uma subárea da Ciências da Saúde que contempla a prevenção, diagnóstico, tratamento e intervenções das doenças que afetam o sistema nervoso central e seus componentes diretos e indiretos, como por exemplo, órgãos periféricos, funções múscoloesqueléticas. Para muitos acadêmicos e até mesmo profissionais da Neurologia, ela ainda é um campo em crescente expansão de conhecimento, que necessita atualização técnica constante devido às expansões tecnológicas dos últimos anos, o que permitiu avaliar mecanismos de ação de fármacos, diagnósticos mais modernos, intervenções cirúrgicas até então restritas apenas a alguns centros médicos de grande desenvolvimento. Portanto, a Editora Pasteur organizou o livro Neurologia: Diagnósticos, Tratamentos e Cirurgias II, com estudos de excelência dentro desta subárea, os quais permitem ao leitor amante da Neurologia se atualizar e buscar maiores conhecimentos.
... Occasionally, faster oscillatory rhythms (thalamocortical spindles and hippocampal ripples) emerge locked at specific SO phases. Properties of SOs like density and amplitude, and their coordination with faster sleep rhythms, have been connected to the improvement in memory performance that can occur across an epoch of sleep (Maquet, 2001;Marshall et al., 2006;Walker and Stickgold, 2006;Diekelmann and Born, 2010;Molle and Born, 2011;Ngo et al., 2013;Rasch and Born, 2013;Dudai et al., 2015;Ladenbauer et al., 2016;Ong et al., 2016;Papalambros et al., 2017;Mikutta et al., 2019). ...
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Sleep slow oscillations (SOs, 0.5–1.5 Hz) are thought to organize activity across cortical and subcortical structures, leading to selective synaptic changes that mediate consolidation of recent memories. Currently, the specific mechanism that allows for this selectively coherent activation across brain regions is not understood. Our previous research has shown that SOs can be classified on the scalp as Global, Local or Frontal, where Global SOs are found in most electrodes within a short time delay and gate long-range information flow during NREM sleep. The functional significance of space-time profiles of SOs hinges on testing if these differential SOs scalp profiles are mirrored by differential depth structure of SOs in the brain. In this study, we built an analytical framework to allow for the characterization of SO depth profiles in space-time across cortical and sub-cortical regions. To test if the two SO types could be differentiated in their cortical-subcortical activity, we trained 30 machine learning classification algorithms to distinguish Global and non-Global SOs within each individual, and repeated this analysis for light (Stage 2, S2) and deep (slow wave sleep, SWS) NREM stages separately. Multiple algorithms reached high performance across all participants, in particular algorithms based on k-nearest neighbors classification principles. Univariate feature ranking and selection showed that the most differentiating features for Global vs. non-Global SOs appeared around the trough of the SO, and in regions including cortex, thalamus, caudate nucleus, and brainstem. Results also indicated that differentiation during S2 required an extended network of current from cortical-subcortical regions, including all regions found in SWS and other basal ganglia regions, and amygdala and hippocampus, suggesting a potential functional differentiation in the role of Global SOs in S2 vs. SWS. We interpret our results as supporting the potential functional difference of Global and non-Global SOs in sleep dynamics.
... tES is not a commonly used procedure during sleep, but recently it has attracted some interest due to the possibility of modulating sleep to enhance memory (Genzel et al., 2014;Rasch and Born, 2007;Walker, 2009). For instance, some studies have explored the use of tES during sleep to modulate brain rhythms that serve a putative function for memory consolidation processes (Binder et al., 2014;Reato et al., 2013a), yet others have tested tES protocols in special populations (Ladenbauer et al., 2016;Prehn-Kristensen et al., 2014;Westerberg et al., 2015). FEM provides an exceptional tool to model current dynamics in the sleeping brain (Gasca et al., 2011), to better understand the physiological mechanisms of the tES (Antonenko et al., 2013;Ellenbogen et al., 2006;Walker, 2009). ...
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Article
A realistic rat brain model was used to simulate current density and electric field distributions under frequencies characteristic of sleeping states (0.8, 5, and 12 Hz). Two anode-electrode setups were simulated: plate vs. screws-anode, both with a cephalic cathode. Our simulations showed that these frequencies have limited impact on electric field and current density; however, the highest frequency evidenced higher values for both variables. The type of electrode setup had a greater effect on current distribution and induced fields. In that sense, the screws setup resulted in higher values. The numeric results obtained are within the range of available data for rodent models using the finite elements method. These modeled effects should be analyzed regarding anatomical consequences (depth of penetration of the currents) and purpose of the experiment (i.e., entrainment of brain oscillations) in the context of sleep research.
... Enhancement in the sigma band was also distributed in parietal areas, confirming previous findings on the topography of fast spindles Mölle et al., 2011).In summary, we observed two distinct effects of phase-locked auditory stimulation on cross-frequency coupling for two frequency bands involved in memory consolidation during sleep. In many previous studies, transcranial direct current stimulation was used to demonstrate the relevance of the delta-sigma coupling for the overnight memory formation (Ladenbauer et al., 2016;Marshall et al., 2006;Westerberg et al., 2015). The global sigma boost observed one second after auditory stimulation could provide the optimal time-window for memory replay, with content specificity encoded in the gamma band. ...
... Nevertheless, most studies rely on manual real-time scoring and delivering stimulation during SWS rather than individual SOs. For example, Marshall et al. [76] and Ladenbauer et al. [77] employed manual online scoring to deliver transcranial direct current stimulation (tDCS) during SWS. All three studies reported an increase in SO power and declarative memory after waking. ...
Thesis
Sleep is a complex physiological process responsible for several developmental, restorative and cognitive processes. Sleep related disorders diminish life quality, and their diagnosis relies on classifying 8-hour polysomnographic (PSG) recordings. Manual scoring is the gold standard for analyzing sleep and is a time consuming task that can only be per- formed by trained experts. We propose SleepBCI, a platform that integrates sleep quality analysis and closed-loop memory enhancement using automatic sleep scoring as its corner- stone. Firstly, real-time sleep staging is carried out through a convolutional deep neural network capable of achieving accuracies of 80-84% on a variable number of channels (1 to 6). Employing the neural networks’ output, we created an automated sleep quality report with objective metrics. This way, we characterized significant differences between healthy individuals and patients suffering from diverse sleep pathologies, such as breathing disor- ders, insomnia and narcolepsy. Furthermore, we implemented a brain-computer interface based on monitoring EEG activity in real time, intended to enhance previously learned memories during deep sleep. We validated it in a controlled study on healthy participants, who performed a word-sound association task before and after sleep. Recall performance after waking was significantly greater for reactivated cues compared with non-reactivated cues. The platform and results presented in this work serve as a proof-of-concept for future sleep technology. It lays the foundation for a take-home device capable of alleviat- ing the workload of physicians, preventing at-risk populations (elderly or obese patients) from unnecessary PSG tests and finally, delivering therapy to slow cognitive impairment or dementia.
... This cued reactivation can lead to benefits in recall for the specific items previously associated with the cues. Second, multiple studies have shown that applying transcranial electrical stimulation (tES) at particular frequencies to the brain during sleep can potentiate endogenous electrophysiological processes, leading to facilitation of memory consolidation and subsequent recognition or recall (Ketz et al., 2018;Ladenbauer et al., 2016;Ladenbauer et al., 2017;Lustenberger et al., 2016;Marshall et al., 2006;Marshall et al., 2004;Westerberg et al., 2015). These studies have demonstrated a general increase in memory retrieval performance following tES during sleep. ...
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Meta-memory involves the ability to correctly judge the accuracy of our memories. The retrieval of memories can be improved using transcranial electrical brain stimulation (tES) during sleep, but evidence for improvements to meta-memory sensitivity is limited. Applying tES can enhance sleepdependent memory consolidation, which along with meta-memory requires the coordination of activity across distributed neural systems, suggesting that examining functional connectivity is important for understanding these processes. Nevertheless, little research has examined how functional connectivity modulations relate to overnight changes in meta-memory sensitivity. Here, we developed a closed-loop short-duration tES method, time-locked to up-states of ongoing slow-wave oscillations, to cue specific memory replays in humans. We measured electroencephalographic (EEG) coherence changes following stimulation pulses, and characterized network alterations with graph theoretic metrics. Using machine learning techniques, we show that pulsed tES elicited network changes in multiple frequency bands, including increased connectivity in the Theta band and increased efficiency in the Spindle band. Additionally, stimulation-induced changes in Beta band path length were predictive of overnight changes in meta-memory sensitivity. These findings add new insights into the growing literature investigating increases in memory performance through brain stimulation during sleep, and highlight the importance of examining functional connectivity to explain its effects.
... Data reported here were taken from baseline measurements of two intervention studies that assessed the effects of oscillatory tDCS during sleep (daytime nap vs night sleep) on cognitive performance (Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation (study 1) & Effects of Brain Stimulation During Nocturnal Sleep on Memory Consolidation (study 2) in young and older healthy subjects and subjects with mild cognitive impairment (MCI)). These studies are described in detail elsewhere [25,26] and included comprehensive assessment of subjective (using sleep diary and sleep questionnaires) and objective sleep-wake behavior among others, as well as neuropsychological testing and structural imaging of the brain using magnetic resonance imaging (MRI). Objective sleep assessment included seven days of accelerometry. ...
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Introduction Many clinical studies reporting accelerometry data use sum score measures such as percentage of time spent in moderate to vigorous activity which do not provide insight into differences in activity patterns over 24 hours, and thus do not adequately depict circadian activity patterns. Here, we present an improved functional data analysis approach to model activity patterns and circadian rhythms from accelerometer data. As a use case, we demonstrated its application in patients with mild cognitive impairment (MCI) and age-matched healthy older volunteers (HOV). Methods Data of two studies were pooled for this analysis. Following baseline cognitive assessment participants were provided with accelerometers for seven consecutive days. A function on scalar regression (FoSR) approach was used to analyze 24 hours accelerometer data. Results Information on 48 HOV (mean age 65 SD 6 years) and 18 patients with MCI (mean age 70, SD 8 years) were available for this analysis. MCI patients displayed slightly lower activity in the morning hours (minimum relative activity at 6:05 am: -41.3%, 95% CI -64.7 to -2.5%, p = 0.031) and in the evening (minimum relative activity at 21:40 am: -48.4%, 95% CI -68.5 to 15.4%, p = 0.001) as compared to HOV after adjusting for age and sex. Discussion Using a novel approach of FoSR, we found timeframes with lower activity levels in MCI patients compared to HOV which were not evident if sum scores of amount of activity were used, possibly indicating that changes in circadian rhythmicity in neurodegenerative disease are detectable using easy-to-administer accelerometry. Clinical trials Effects of Brain Stimulation During Nocturnal Sleep on Memory Consolidation in Patients With Mild Cognitive Impairments, ClinicalTrial.gov identifier: NCT01782391 . Effects of Brain Stimulation During a Daytime Nap on Memory Consolidation in Patients With Mild Cognitive Impairment, ClinicalTrial.gov identifier: NCT01782365 .
... It would for example allow for computing optimal interventions for changing the power of certain brain rhythms, which can be monitored by electroencephalography and which are common control targets in clinical settings (cf. [75]). As shown in other computational and physiological studies [58,76] and emphasized again by our results, the timing of the control inputs may also be crucial for successful interventions. ...
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We apply the framework of optimal nonlinear control to steer the dynamics of a whole-brain network of FitzHugh-Nagumo oscillators. Its nodes correspond to the cortical areas of an atlas-based segmentation of the human cerebral cortex, and the inter-node coupling strengths are derived from Diffusion Tensor Imaging data of the connectome of the human brain. Nodes are coupled using an additive scheme without delays and are driven by background inputs with fixed mean and additive Gaussian noise. Optimal control inputs to nodes are determined by minimizing a cost functional that penalizes the deviations from a desired network dynamic, the control energy, and spatially non-sparse control inputs. Using the strength of the background input and the overall coupling strength as order parameters, the network's state-space decomposes into regions of low and high activity fixed points separated by a high amplitude limit cycle all of which qualitatively correspond to the states of an isolated network node. Along the borders, however, additional limit cycles, asynchronous states and multistability can be observed. Optimal control is applied to several state-switching and network synchronization tasks, and the results are compared to controllability measures from linear control theory for the same connectome. We find that intuitions from the latter about the roles of nodes in steering the network dynamics, which are solely based on connectome features, do not generally carry over to nonlinear systems, as had been previously implied. Instead, the role of nodes under optimal nonlinear control critically depends on the specified task and the system's location in state space. Our results shed new light on the controllability of brain network states and may serve as an inspiration for the design of new paradigms for non-invasive brain stimulation.
... Repetitions become an essential variable since change does not manifest in the same way in the 10 or 20 sessions cut. To think about the benefit of this, it is interesting to consider that other studies in older adults have shown that enhancing slow oscillation leads to a memory enhancement (Ladenbauer et al., 2016;Westerberg et al., 2015). ...
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Previous investigations have tried to prove the effectiveness of interventions that seek to improve rest in elderly people. Neurofeedback (NF) is an intervention aimed to train self-regulation of brain functions, which, in other populations, has proven to be beneficial for rest quality as well. e objective of this experimental study was to determine the effect of NF on sleep quality in elderly women that stay in nursing homes or institutions that care for the elderly by comparing the scores of 14 participants. No statistically significant differences were observed between the NF group and the control group; however, sleep quality improved in the NF group and alpha frequency increased significantly in participants aer the intervention. Although there is evidence of modification in physiological indicators and increased sleep quality in the NF group, it is likely that because of the living conditions of the participants, the effects have not been powerful enough to manifest themselves in the sleep quality evaluation.
... tDCS showed improvement in SWA and overnight memory retention in young adults (Marshall et al., 2004(Marshall et al., , 2006. Some studies demonstrated enhanced slow oscillation (<1 Hz) with improved memory (Westerberg et al., 2015;Ladenbauer et al., 2016). Studies utilizing acoustic stimulation methods during sleep can increase SWA, especially slow oscillation (<1 Hz), and improve sleep-dependent memory retention both in young (Ngo et al., 2013(Ngo et al., , 2015Kawai et al., 2016a;Leminen et al., 2017;Papalambros et al., 2017;Ong et al., 2018) and older adults (Papalambros et al., 2017). ...
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Article
Objective: In recognition of the mixed associations between traditionally scored slow wave sleep and memory, we sought to explore the relationships between slow wave sleep, electroencephalographic (EEG) power spectra during sleep and overnight verbal memory retention in older adults. Design, Setting, Participants, and Measurements: Participants were 101 adults without dementia (52% female, mean age 70.3 years). Delayed verbal memory was first tested in the evening prior to overnight polysomnography (PSG). The following morning, subjects were asked to recall as many items as possible from the same List (overnight memory retention; OMR). Partial correlation analyses examined the associations of delayed verbal memory and OMR with slow wave sleep (SWS) and two physiologic EEG slow wave activity (SWA) power spectral bands (0.5–1 Hz slow oscillations vs. 1–4 Hz delta activity). Results: In subjects displaying SWS, SWS was associated with enhanced delayed verbal memory, but not with OMR. Interestingly, among participants that did not show SWS, OMR was significantly associated with a higher slow oscillation relative power, during NREM sleep in the first ultradian cycle, with medium effect size. Conclusions: These findings suggest a complex relationship between SWS and memory and illustrate that even in the absence of scorable SWS, older adults demonstrate substantial slow wave activity. Further, these slow oscillations (0.5–1 Hz), in the first ultradian cycle, are positively associated with OMR, but only in those without SWS. Our findings raise the possibility that precise features of slow wave activity play key roles in maintaining memory function in healthy aging. Further, our results underscore that conventional methods of sleep evaluation may not be sufficiently sensitive to detect associations between SWA and memory in older adults.
... Thus, older adults may not achieve sufficient SWA during naps to consolidate memories. Indeed, transcranial slow-oscillatory stimulation that enhances nap SWA led to improved nap-dependent memory consolidation in older adults [57,58]. ...
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Purpose of Review Napping is a common behavior across age groups. While studies have shown a benefit of overnight sleep on memory consolidation, given differences in nap frequency, composition, and intent, it is important to consider whether naps serve a memory function across development and aging. Recent Findings We review studies of the role of naps in declarative, emotional, and motor procedural memory consolidation across age groups. Recent findings in both developmental and aging populations find that naps benefit learning of many tasks but may require additional learning or sleep bouts compared to young adult populations. These studies have also identified variations in nap physiology based on the purpose of the nap, timing of the nap, or age. Summary These studies lend to our understanding of the function of sleep, and the potential for naps as an intervention for those with reduced nighttime sleep or learning impairments.
... Augmentation of slow oscillation activity by TDCS has demonstrated benefit to declarative memory in both young [205][206][207] and older [208,209] healthy participants, and in both nocturnal [206] and nap [205,207,208] protocols. In Cellini et al. [207], this was accompanied by an overall increase in time spent in slow-wave sleep, and cognitive benefits persisted at 48 h. ...
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Article
Sleep dysfunction is highly prevalent across the spectrum of neurodegenerative conditions and is a key determinant of quality of life for both patients and their families. Mounting recent evidence also suggests that such dysfunction exacerbates cognitive and affective clinical features of neurodegeneration, as well as disease progression through acceleration of pathogenic processes. Effective assessment and treatment of sleep dysfunction in neurodegeneration is therefore of paramount importance; yet robust therapeutic guidelines are lacking, owing in part to a historical paucity of effective treatments and trials. Here, we review the common sleep abnormalities evident in neurodegenerative disease states and evaluate the latest evidence for traditional and emerging interventions, both pharmacological and nonpharmacological. Interventions considered include conservative measures, targeted treatments of specific clinical sleep pathologies, established sedating and alerting agents, melatonin, and orexin antagonists, as well as bright light therapy, behavioral measures, and slow-wave sleep augmentation techniques. We conclude by providing a suggested framework for treatment based on contemporary evidence and highlight areas that may emerge as major therapeutic advances in the near future.
... Of course, the usefulness of tDCS is not limited to counteracting cognitive decline but has also proven effective in many other domains, including geriatric depression (Gálvez et al., 2015), motor (Zandvliet et al., 2018) and language performance (Meinzer et al., 2016) after stroke, and Parkinson's disease (Yotnuengnit et al., 2018). Similarly to acoustic stimulation (Wunderlin et al., 2020 (in this issue)), the potency of tDCS to enhance parameters of sleep (Ladenbauer et al., 2016) as well as to lengthen total sleep time (Frase et al., 2016), which is of particular importance in elderly who exhibit an aberrant sleep pattern, has also been explored. Many of the considerations described below also pertain to the application of tDCS in those clinical populations. ...
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Article
Ageing involves significant neurophysiological changes that are both systematic while at the same time exhibiting divergent trajectories across individuals. These changes underlie cognitive impairments in elderly while also affecting the response of aged brains to interventions like transcranial direct current stimulation (tDCS). While the cognitive benefits of tDCS are more variable in elderly, older adults also respond differently to stimulation protocols compared to young adults. The age-related neurophysiological changes influencing the responsiveness to tDCS remain to be addressed in-depth. We review and discuss the premise that, in comparison to the better calibrated brain networks present in young adults, aged systems perform further away from a homoeostatic set-point. We argue that this age-related neurophysiological deviation from the homoeostatic optimum extends the leeway for tDCS to modulate the aged brain. This promotes the potency of immediate tDCS effects to induce directional plastic changes towards the homoeostatic equilibrium despite the impaired plasticity induction in elderly. We also consider how age-related neurophysiological changes pose specific challenges for tDCS that necessitate proper adaptations of stimulation protocols. Appreciating the distinctive properties of aged brains and the accompanying adjustment of stimulation parameters can increase the potency and reliability of tDCS as a treatment avenue in older adults.
... Enhancement in the sigma band was also distributed in parietal areas, confirming previous findings on the topography of fast spindles 49,56 .In summary, we observed two distinct effects of closed-loop auditory stimulation on cross-frequency coupling for two frequency bands involved in memory consolidation during sleep. In many previous studies, transcranial direct current stimulation was used to demonstrate the relevance of the delta-sigma coupling for the overnight memory formation 24,57,58 . The global sigma boost observed one second after auditory stimulation could provide the optimal time-window for memory replay, with content specificity encoded in the gamma band. ...
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Article
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.
... The specific brain oscillations by applying transcranial electrical stimulation techniques to enhance sleep quality and memory processes have become an intriguing field of research [8]. Modulating brain areas, which are involved in the sleep process, can be effective in sleep dynamics and promote sleep quality [9,10]. Based on the conducted studies, there is a link between electrical stimulation of the specific areas of cortex and sleep quality [11]. ...
Article
Background: Patients under Methadone Maintenance Therapy (MMT) are susceptible to several problems, including sleep disturbances and risk of relapse. The present study aimed to assess the effect of transcranial direct current stimulation (tDCS) on sleep quality of addicts under MMT. Methods: This clinical trial was conducted on 27 male patients who underwent maintenance methadone therapy in MMT clinics of Mashhad City, Iran. They were divided into the experimental and sham groups. The experimental group received seven 20-min sessions of tDCS every other day. In the sham group, the electrical current was delivered for a few seconds, but the electrodes were remained to the end of the session. Sleep quality was measured at baseline, during, and after the intervention by Pittsburg Sleep Quality Index (PSQI). The obtained data were analyzed by descriptive statistics such as mean and standard deviation and inferential statistics, such as t test, Chi-square, Mann Whitney, and Fischer exact test in SPSS v. 25. Results: The difference between the two groups after tDCS in sleep duration was significant (P=0.04). In the experimental group, the total score of sleep had a reducing trend (P
... Experiments to counter such impairments by enhancing sleep are highly topical and have been successfully trialled with several stimulation modalities in young and older adults [28][29][30][31][32] . Auditory closed-loop stimulation has proven to be a particularly promising technique 33 , which consists of detecting endogenous SOs and applying brief auditory stimuli during their positive peaks. ...
Article
Study Objectives: Cortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate memory consolidation, both of which are reduced with age. Experiments utilising auditory closed-loop stimulation to enhance these oscillations showed great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups. We examined the possibility of enhancing SOs and performance on different memory tasks in a healthy middle-aged population using this stimulation and contrast effects to younger adults. Methods: In a within-subject design, 17 subjects (55.7±1.0 years) received auditory stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to a previous younger cohort (n = 11, 24.2±0.9 years). Results: Overnight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups. Conclusions: Our findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations.
... Experiments to counter such impairments by enhancing sleep are highly topical and have been successfully trialled with several stimulation modalities in young and older adults [28][29][30][31][32] . Auditory closed-loop stimulation has proven to be a particularly promising technique 33 , which consists of detecting endogenous SOs and applying brief auditory stimuli during their positive peaks. ...
Full-text available
Article
Study Objectives Cortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate memory consolidation, both of which are reduced with age. Experiments utilising auditory closed-loop stimulation to enhance these oscillations showed great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups. We examined the possibility of enhancing SOs and performance on different memory tasks in a healthy middle-aged population using this stimulation and contrast effects to younger adults. Methods In a within-subject design, 17 subjects (55.7±1.0 years) received auditory stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to a previous younger cohort (n = 11, 24.2±0.9 years). Results Overnight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups. Conclusions Our findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations.
... Slow frequency otDCS mimicking slow-wave activity has been tested in older adults during afternoon naps. Westerberg targeted SWA with a subsequent improvement in word-pair performance [11], while Ladenbauer enhanced 1Hz oscillations and fast sleep spindles power, leading to a benefit in a visual memory task [215]. Other studies with slow-wave tACS and otDCS administered overnight in the elderly failed to replicate the beneficial enhancement of SWA and memory consolidation [216,217]. ...
Article
As we age, sleep patterns undergo significant modifications in micro and macrostructure, worsening cognition, and quality of life. These are associated with remarkable brain changes, like deterioration in synaptic plasticity, gray and white matter, and significant modifications in hormone levels. Sleep alterations are also a core component of mild cognitive impairment (MCI) and Alzheimer’s Disease (AD). AD night time is characterized by a gradual decrease in slow-wave activity and a substantial reduction of REM sleep. Sleep abnormalities can accelerate AD pathophysiology, promoting the accumulation of amyloid-β (Aβ) and phosphorylated tau. Thus, interventions that target sleep disturbances in elderly people and MCI patients have been suggested as a possible strategy to prevent or decelerate conversion to dementia. Although cognitive-behavioral therapy and pharmacological medications are still first-line treatments, despite being scarcely effective, new interventions have been proposed, such as sensory stimulation and Noninvasive Brain Stimulation (NiBS). The present review outlines the current state of the art of the relationship between sleep modifications in healthy aging and the neurobiological mechanisms underlying age-related changes. Furthermore, we provide a critical analysis showing how sleep abnormalities influence the prognosis of AD pathology by intensifying Aβ and tau protein accumulation. We discuss potential therapeutic strategies to target sleep disruptions and conclude that there is an urgent need for testing new therapeutic sleep interventions.
... Regarding fact recognition and object priming, however, no differences between the stimulation and a sham condition were detected. Along similar lines, Ladenbauer et al. [97] demonstrated increased retention of pictures after SO-tDCS during an afternoon nap, whereas object location and verbal memory remained unaffected. When acoustically enhancing SWA in older adults, Papalambros et al. [100] demonstrated greater overnight improvements in word pair recall. ...
Article
Sleep benefits the stabilization of newly acquired information – a process known as memory consolidation. Age-related alterations in sleep physiology may affect memory consolidation and account for reduced episodic memory performance in healthy older individuals. The striking parallelism of age-related changes in sleep and episodic memory has provoked a considerable increment in empirical studies investigating the link between age-related changes in sleep and memory. Still, evidence remains inconclusive under which circumstances and by which mechanisms memory consolidation is affected during aging. In this review we provide an exhaustive summary of the status quo of research on episodic memory consolidation during sleep in healthy aging. On this basis, we derive a cohesive explanatory framework to understand age-related changes in consolidation mechanisms during sleep. Consolidation impairments are not solely caused by sleep changes but arise in synergy with age-related alterations in brain structure and neuromodulation. We argue that sleep oscillations during deep non-rapid eye movement (NREM) sleep guide the reactivation, integration, and redistribution of memory traces. Neuromodulators supporting these mechanisms change in old age. In combination with alterations in brain structure, the generation of sleep oscillations during NREM sleep is impaired, their coordination becomes diffuse, and the processes necessary to render stable episodic memories are impaired.
Article
Over the past few decades, the importance of sleep has become increasingly recognized for many physiologic functions, including cognition. Many studies have reported the deleterious effect of sleep loss or sleep disruption on cognitive performance. Beyond ensuring adequate sleep quality and duration, discovering methods to enhance sleep to augment its restorative effects is important to improve learning in many populations, such as the military, students, age-related cognitive decline, and cognitive disorders.
Article
Background: Oscillatory rhythms during sleep, such as slow oscillations (SOs) and spindles and, most importantly, their coupling, are thought to underlie processes of memory consolidation. External slow oscillatory transcranial direct current stimulation (so-tDCS) with a frequency of 0.75 Hz has been shown to improve this coupling and memory consolidation; however, effects varied quite markedly between individuals, studies, and species. In this study, we aimed to determine how precisely the frequency of stimulation must match the naturally occurring SO frequency in individuals to best improve SO-spindle coupling. Moreover, we systematically tested stimulation durations necessary to induce changes. Materials and methods: We addressed these questions by comparing so-tDCS with individualized frequency to standardized frequency of 0.75 Hz in a within-subject design with 28 older participants during napping while stimulation train durations were systematically varied between 30 seconds, 2 minutes, and 5 minutes. Results: Stimulation trains as short as 30 seconds were sufficient to modulate the coupling between SOs and spindle activity. Contrary to our expectations, so-tDCS with standardized frequency indicated stronger aftereffects regarding SO-spindle coupling than individualized frequency. Angle and variance of spindle maxima occurrence during the SO cycle were similarly modulated. Conclusions: In sum, short stimulation trains were sufficient to induce significant changes in sleep physiology, allowing for more trains of stimulation, which provides methodological advantages and possibly even larger behavioral effects in future studies. Regarding individualized stimulation frequency, further options of optimization need to be investigated, such as closed-loop stimulation, to calibrate stimulation frequency to the SO frequency at the time of stimulation onset. Clinical trial registration: The Clinicaltrials.gov registration number for the study is NCT04714879.
Chapter
O livro enfatiza fatores que regem a vida humana do início ao fim e que podem ser muito diferentes entre indivíduos e populações: 1) caracteres genéticos herdados diretamente de nossos pais e indiretamente de nossos ancestrais, os quais permanecem relativamente estáveis ao longo da vida; 2) fatores ambientais (alimentação, condição e estilo de vida) até certo ponto controláveis, sendo a alimentação o mais importante. A primeira parte do livro trata da definição e da conceituação do processo de envelhecimento e seus efeitos na saúde. Seguem-se a apresentação e a discussão de mecanismos que promovem degradação molecular e celular responsáveis por distúrbios metabólicos que podem resultar em doenças crônico-degenerativas. A maior parte do texto é dedicada à apresentação de alimentos e compostos bioativos que agem combatendo o envelhecimento precoce e retardando doenças da idade. Por fim, faz-se uma discussão sobre conceitos de dietas saudáveis com sugestões para pesquisas, visando melhorar o perfil alimentar do brasileiro.
Article
Substantial empirical evidence suggests that sleep benefits the consolidation and reorganization of learned information. Consequently, the concept of “sleep-dependent memory consolidation” is now widely accepted by the scientific community, in addition to influencing public perceptions regarding the functions of sleep. There are, however, numerous studies that have presented findings inconsistent with the sleep-memory hypothesis. Here, we challenge the notion of “sleep-dependency” by summarizing evidence for effective memory consolidation independent of sleep. Plasticity mechanisms thought to mediate or facilitate consolidation during sleep (e.g., neuronal replay, reactivation, slow oscillations, neurochemical milieu) also operate during non-sleep states, particularly quiet wakefulness, thus allowing for the stabilization of new memories. We propose that it is not sleep per se, but the engagement of plasticity mechanisms, active during both sleep and (at least some) waking states, that constitutes the critical factor determining memory formation. Thus, rather than playing a "critical" role, sleep falls along a continuum of behavioral states that vary in their effectiveness to support memory consolidation at the neural and behavioral level.
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Preparation of this publication was partially supported by the National Institute of Mental Health of the National Institutes of Health under Award Numbers R01MH122477, R01MH101547, and R21MH105557. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Caroline Lustenberger is supported by the Swiss National Science Foundation (PZ00P3_179795). The authors thank the contributors to the previous version of this book chapter for laying the groundwork for this version (in alphabetical order): Sankaraleengam Alagapan, Michael R. Boyle1, Franz Hamilton, Guoshi Li, and Stephen L. Schmidt. Flavio Frohlich is the founder, shareholder, and chief scientific officer of Pulvinar Neuro, which did not play any role in the writing of this chapter. The other authors have no conflicts to report.
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Slow Wave Activity (SWA), the low frequency (<4 Hz) oscillations that characterize Slow Wave Sleep (SWS) are thought to relate causally to declarative memory consolidation during nocturnal sleep. Evidence is conflicting relating SWA to memory consolidation during nap however. We applied transcranial alternating current stimulation (tACS) - which, with a cross-hemispheric electrode montage (F3 and F4 - International 10:20 EEG system), is able to disrupt brain oscillations-to determine if disruption of low frequency oscillation generation during afternoon nap is causally related to disruption in declarative memory consolidation. Eight human subjects each participated in stimulation and sham nap sessions. A verbal paired associate learning (PAL) task measured memory changes. During each nap period, five 5-min stimulation (0.75 Hz cross-hemispheric frontal tACS) or sham intervals were applied with 1-min post-stimulation intervals (PSI's). Spectral EEG power for Slow (0.7-0.8 Hz), Delta (1.0-4.0 Hz), Theta (4.0-8.0 Hz), Alpha (8.0-12.0 Hz), and Spindle-range (12.0-14.0) frequencies was analyzed during the 1-min preceding the onset of stimulation and the 1-min PSI's. As hypothesized, power reduction due to stimulation positively correlated with reduction in word-pair recall post-nap specifically for Slow (P < 0.0022) and Delta (P < 0.037) frequency bands. These results provide preliminary evidence suggesting a causal and specific role of SWA in declarative memory consolidation during nap. Copyright © 2015 Elsevier Inc. All rights reserved.
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The Leipzig Corpora Collection offers free online access to 136 monolingual dictionaries enriched with statistical information. In this paper we describe current advances of the project in collecting and processing text data automatically for a large number of languages. Our main interest lies in languages of "low density", where only few text data exists online. The aim of this approach is to create monolingual dictionaries and statistical information for a high number of new languages and to expand the existing dictionaries, opening up new possibilities for linguistic typology and other research. Focus of this paper will be set on the infrastructure for the automatic acquisition of large amounts of monolingual text in many languages from various sources. Preliminary results of the collection of text data will be presented. The mainly language-independent framework for preprocessing, cleaning and creating the corpora and computing the necessary statistics will also be depicted.
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Background Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. Objective Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. Methods: 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. Results Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. Conclusion These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD.