Selection of stimulus parameters for enhancing slow wave sleep events with a Neural-field theory thalamocortical computational model

AbstractSlow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates to memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events’ co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0º, 45º, and 90º of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0º stimulation produces better results in the power and number of SO and SP than the rhythmic or aleatory stimulation. On the other hand, stimulating at 45º or 90º change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0º phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.Author summaryDuring the non-REM (NREM) phase of sleep, events that are known as slow oscillations (SO) and spindles (SP) can be detected by EEG. These events have been associated with the consolidation of declarative memories and learning. Thus, there is an ongoing interest in promoting them during sleep by non-invasive manipulations such as sensory stimulation. In this paper, we used a computational model of brain activity that generates SO and SP, to investigate which type of sensory stimulus –shape, amplitude, duration, periodicity– would be optimal for increasing the events’ frequency and their co-occurrence. We found that a decreasing ramp of 50 ms duration is the most effective. The effectiveness increases when the stimulus pulse is delivered in a closed-loop configuration triggering the pulse at a target phase of the ongoing SO activity. A desirable secondary effect is to promote SPs at the rising phase of the SO oscillation.

Download Full-text

Selection of stimulus parameters for enhancing slow wave sleep events with a neural-field theory thalamocortical model

PLoS Computational Biology ◽

10.1371/journal.pcbi.1008758 ◽

2021 ◽

Vol 17 (7) ◽

pp. e1008758

Author(s):

Felipe A. Torres ◽

Patricio Orio ◽

María-José Escobar

Keyword(s):

Slow Wave ◽

Memory Consolidation ◽

Closed Loop ◽

Slow Wave Sleep ◽

Brain Activity ◽

Sleep Spindles ◽

Mean Field Model ◽

Cross Point ◽

Slow Oscillations ◽

Closed Loop Stimulation

Slow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates to memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events’ co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0°, 45°, and 90° of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0° stimulation produces better results in the power and number of SO and SP than the rhythmic or random stimulation. On the other hand, stimulating at 45° or 90° change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0° phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.

Download Full-text

Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age

SLEEP ◽

10.1093/sleep/zsaa111 ◽

2020 ◽

Vol 43 (12) ◽

Cited By ~ 2

Author(s):

Jules Schneider ◽

Penelope A Lewis ◽

Dominik Koester ◽

Jan Born ◽

Hong-Viet V Ngo

Keyword(s):

Memory Consolidation ◽

Closed Loop ◽

Temporal Dynamics ◽

Age Groups ◽

Recognition Task ◽

Auditory Stimulation ◽

Sleep Spindles ◽

Slow Oscillations ◽

Up States ◽

Closed Loop Stimulation

Abstract Study Objectives Cortical slow oscillations (SOs) and thalamocortical sleep spindles hallmark slow wave sleep and facilitate memory consolidation, both of which are reduced with age. Experiments utilizing 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.

Download Full-text

Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age

10.1101/2019.12.15.876847 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jules Schneider ◽

Penelope A. Lewis ◽

Dominik Koester ◽

Jan Born ◽

Hong-Viet V. Ngo

Keyword(s):

Memory Consolidation ◽

Closed Loop ◽

Age Groups ◽

Auditory Stimulation ◽

Sleep Spindles ◽

Older Population ◽

Slow Oscillations ◽

Up States ◽

Older Subjects ◽

Closed Loop Stimulation

AbstractBackgroundCortical slow oscillations (SOs) and thalamo-cortical sleep spindles hallmark slow wave sleep and facilitate sleep-dependent memory consolidation. Experiments utilising auditory closed-loop stimulation to enhance these oscillations have shown great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups.ObjectiveWe examined the possibility of enhancing SOs and performance on different memory tasks in a healthy older population using auditory closed-loop stimulation and contrast effects to a young adult cohort.MethodsIn a within-subject design, subjects (n = 17, 55.7 ± 1.0 years, 9 female) received auditory click 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 those reported previously in a younger cohort (n = 11, 24.2 ± 0.9 years, 8 female).ResultsOvernight 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.ConclusionsOur 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.HighlightsAuditory closed-loop stimulation induced SOs and sleep spindles in older subjectsStimulation effects were reduced and overall susceptibility diminished with ageSlow oscillation and sleep spindle dynamics deviated from those in younger subjectsStimulation shows no evidence for memory effect in older subjects

Download Full-text

Dysfunctional Overnight Memory Consolidation in Patients with Schizophrenia in Comparison to Healthy Controls: Disturbed Slow-Wave Sleep as Contributing Factor?

Neuropsychobiology ◽

10.1159/000517858 ◽

2021 ◽

pp. 1-12

Author(s):

Sara Lena Weinhold ◽

Julia Lechinger ◽

Jasper Ittel ◽

Romina Ritzenhoff ◽

Henning Johannes Drews ◽

...

Keyword(s):

Linear Relationship ◽

Slow Wave ◽

Memory Consolidation ◽

Slow Wave Sleep ◽

Declarative Memory ◽

Sleep Spindles ◽

Sleep Spindle ◽

Delta Power ◽

Sleep Parameters ◽

Spindle Power

Introduction: Memory deficiency has been shown in schizophrenia patients, but results on the role of sleep parameters in overnight consolidation of associative verbal memory are still missing. Therefore, the aim of our study was to elucidate underlying processes of impaired sleep-related consolidation of associative word pairs in schizophrenia including standard sleep parameters as well as sleep spindle counts and spectral analysis. Methods: Eighteen stably medicated schizophrenia patients and 24 healthy age-matched controls performed an associative declarative memory task before and after polysomnographic recordings. Part of the participants expected verbal associative memory testing in the morning, while the others did not. Furthermore, participants filled in self-rating questionnaires of schizophrenia-typical experiences (Eppendorf Schizophrenia Inventory [ESI] and Psychotic Symptom Rating Scale). Results: Schizophrenia patients performed worse in verbal declarative memory in the evening as well as in overnight consolidation (morning compared to evening performance). While duration of slow-wave sleep was nearly comparable between groups, schizophrenia patients showed lower sleep spindle count, reduced delta power during slow-wave sleep, and reduced spindle power during the slow oscillation (SO) up-state. In healthy but not in schizophrenia patients, a linear relationship between overnight memory consolidation and slow-wave sleep duration as well as delta power was evident. No significant effect with respect to the expectation of memory retrieval was evident in our data. Additionally, we observed a negative linear relationship between total number of sleep spindles and ESI score in healthy participants. Discussion/Conclusion: As expected, schizophrenia patients showed deficient overnight verbal declarative memory consolidation as compared to healthy controls. Reduced sleep spindles, delta power, and spindle power during the SO up-state may link sleep and memory deficiency in schizophrenia. Additionally, the absence of a linear relationship between sleep-related memory consolidation and slow-wave sleep as well as delta power suggests further functional impairments in schizophrenia. Note that this conclusion is based on observational data. Future studies should investigate if stimulation of delta waves during sleep could improve memory performance and thereby quality of life in schizophrenia.

Download Full-text

Stimulation augments spike sequence replay and memory consolidation during slow-wave sleep

10.1101/670091 ◽

2019 ◽

Author(s):

Yina Wei ◽

Giri P Krishnan ◽

Lisa Marshall ◽

Thomas Martinetz ◽

Maxim Bazhenov

Keyword(s):

Slow Wave ◽

Memory Consolidation ◽

Temporal Pattern ◽

Slow Wave Sleep ◽

Sensory Stimulation ◽

Slow Waves ◽

Memory Traces ◽

Spatio Temporal ◽

Synaptic Level

AbstractNewly acquired memory traces are spontaneously reactivated during slow-wave sleep (SWS), leading to the consolidation of recent memories. Empirical studies found that sensory stimulation during SWS selectively enhances memory consolidation and the effect depends on the phase of stimulation. In this new study, we aimed to understand the mechanisms behind the role of sensory stimulation on memory consolidation using computational models implementing effects of neuromodulators to simulate transitions between awake and SWS sleep, and synaptic plasticity to allow the change of synaptic connections due to the training in awake or replay during sleep. We found that when closed-loop stimulation was applied during the Down states (900-2700) of sleep slow oscillation, particularly right before transition from Down to Up state, it significantly affected the spatio-temporal pattern of the slow-waves and maximized memory replay. In contrast, when the stimulation was presented during the Up states (2700-3600 and 00-900), it did not have a significant impact on the slow-waves or memory performance after sleep. For multiple memories trained in awake, presenting stimulation cues associated with specific memory trace could selectively augment replay and enhance consolidation of that memory and interfere with consolidation of the others (particularly weak) memories. Our study proposes a synaptic level mechanism of how memory consolidation is affected by sensory stimulation during sleep.Significance statementStimulation, such as training-associated cues or auditory stimulation, during sleep can augment consolidation of the newly encoded memories. In this study, we used a computational model of the thalamocortical system to describe the mechanisms behind the role of stimulation in memory consolidation during slow-wave sleep. Our study suggested that stimulation preferentially strengthens the memory traces when delivered at specific phase of slow oscillations just before Down to Up state transition when it makes the largest impact on the spatio-temporal pattern of sleep slow waves. In the presence of multiple memories, presenting sensory cues during sleep could selectively strengthen selected memories. Our study proposes a synaptic level mechanism of how memory consolidation is affected by sensory stimulation during sleep.

Download Full-text

Effects of Olanzapine on Slow Wave Sleep, Sleep Spindles and Sleep-Related Memory Consolidation in Schizophrenia

Pharmacopsychiatry ◽

10.1055/s-2007-1004592 ◽

2008 ◽

Vol 41 (3) ◽

pp. 92-99 ◽

Cited By ~ 47

Author(s):

R. Göder ◽

G. Fritzer ◽

B. Gottwald ◽

B. Lippmann ◽

M. Seeck-Hirschner ◽

...

Keyword(s):

Slow Wave ◽

Memory Consolidation ◽

Slow Wave Sleep ◽

Sleep Spindles

Download Full-text

Sleep spindles facilitate selective memory consolidation

10.1101/2020.04.03.022434 ◽

2020 ◽

Cited By ~ 4

Author(s):

Dan Denis ◽

Dimitris Mylonas ◽

Craig Poskanzer ◽

Verda Bursal ◽

Jessica D. Payne ◽

...

Keyword(s):

Memory Consolidation ◽

Slow Wave Sleep ◽

Sleep Spindles ◽

Slow Oscillations ◽

Initial Strength ◽

Long Term Storage ◽

Cortical Oscillations ◽

Memory Traces ◽

New Evidence ◽

The Brain

AbstractSleep has been shown to be critical for memory consolidation, and recent research has demonstrated that this consolidation effect is selective, with certain memories being prioritized for strengthening. Initial strength of a memory appears to be one metric the brain uses to prioritize memory traces for sleep-based consolidation, but the role of consolidation-mediating cortical oscillations, such as sleep spindles and slow oscillations, has not been explored. Here, N=54 participants studied pairs of words to three distinct encoding strengths, with recall being tested immediately following learning and again six hours later. N=36 had a two-hour afternoon nap opportunity following learning, whilst the remaining (n=18) remained awake throughout. Results showed a selective benefit of sleep on memory, with sleep preferentially consolidating weakly encoded items (p=.003). The magnitude of this effect (d=0.90, 95% CI=0.29-1.50) was similar when compared to a previous study examining the benefits of a full night of sleep (d=1.36, 95% CI=0.59-2.12). Within the nap group, consolidation of weakly encoded items was associated with sleep spindle density during slow wave sleep (r=.48, p=.003). This association was present when separately examining spindles coupled (r=.41, p=.013), and uncoupled (r=.44, p=.007) with slow oscillations. Memory was significantly better in individuals who showed an amount of slow oscillation-spindle coupling that was greater than what would be expected by chance (p=.006, d=1.15). These relationships were unique to weakly encoded items, with spindles not correlating with memory for intermediate or strong items. This suggests that sleep spindles facilitate selective memory consolidation, guided in part by memory strength.Significance statementGiven the countless pieces of information we encode each day, how does the brain select which memories to commit to long-term storage? Sleep is known to aid in memory consolidation, but less research has examined which memories are prioritized to receive this benefit. Here, we found that compared to staying awake, sleep was associated with better memory for weakly encoded information. This suggests sleep helps to rescue weak memory traces from being forgotten. Sleep spindles, a hallmark oscillation of non-rapid eye movement sleep, mediates consolidation processes. We extended this to show that spindles selectively facilitated consolidation of weakly encoded memories. This provides new evidence for the selective nature of sleep-based consolidation and elucidates a physiological correlate of this preferential benefit.

Download Full-text