Auditory Closed-loop Stimulation Research Articles

A closed-loop auditory stimulation approach selectively modulates alpha oscillations and sleep onset dynamics in humans.

Alpha oscillations play a vital role in managing the brain's resources, inhibiting neural activity as a function of their phase and amplitude, and are changed in many brain disorders. Developing minimally invasive tools to modulate alpha activity and identifying the parameters that determine its response to exogenous modulators is essential for the implementation of focussed interventions. We introduce Alpha Closed-Loop Auditory Stimulation (αCLAS) as an EEG-based method to modulate and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across a series of independent experiments, we demonstrate that αCLAS alters alpha power, frequency, and connectivity in a phase, amplitude, and topography-dependent manner. Using single-pulse-αCLAS, we show that the effects of auditory stimuli on alpha oscillations can be explained within the theoretical framework of oscillator theory and a phase-reset mechanism. Finally, we demonstrate the functional relevance of our approach by showing that αCLAS can interfere with sleep onset dynamics in a phase-dependent manner.

0138 Effects of Slow Oscillation Enhancement During NREM Sleep Using Closed-loop Auditory Stimulation on Anxiety

0138 Effects of Slow Oscillation Enhancement During NREM Sleep Using Closed-loop Auditory Stimulation on Anxiety

Closed-loop auditory stimulation of slow-wave sleep in chronic insomnia: a pilot study.

Insomnia is a prevalent and disabling condition whose treatment is not always effective. This pilot study explores the feasibility and effects of closed-loop auditory stimulation (CLAS) as a potential non-invasive intervention to improve sleep, its subjective quality, and memory consolidation in patients with insomnia. A total of 27 patients with chronic insomnia underwent a crossover, sham-controlled study with 2 nights of either CLAS or sham stimulation. Polysomnography was used to record sleep parameters, while questionnaires and a word-pair memory task were administered to assess subjective sleep quality and memory consolidation. The initial analyses included 17 patients who completed the study, met the inclusion criteria, and received CLAS. From those, 10 (58%) received only a small number of stimuli. In the remaining seven (41%) patients with sufficient CLAS, we evaluated the acute and whole-night effect on sleep. CLAS led to a significant immediate increase in slow oscillation (0.5-1 Hz) amplitude and activity, and reduced delta (1-4 Hz) and sigma/sleep spindle (12-15 Hz) activity during slow-wave sleep across the whole night. All these fundamental sleep rhythms are implicated in sleep-dependent memory consolidation. Yet, CLAS did not change sleep-dependent memory consolidation or sleep macrostructure characteristics, number of arousals, or subjective perception of sleep quality. Results showed CLAS to be feasible in patients with insomnia. However, a high variance in the efficacy of our automated stimulation approach suggests that further research is needed to optimise stimulation protocols to better unlock potential CLAS benefits for sleep structure and subjective sleep quality in such clinical settings.

Modulation of sleep perception through auditory closed-loop stimulation

Modulation of sleep perception through auditory closed-loop stimulation

Closed-loop auditory stimulation (CLAS) of slow-wave sleep in mouse models of neurodegeneration

Closed-loop auditory stimulation (CLAS) of slow-wave sleep in mouse models of neurodegeneration

REM sleep alpha and theta oscillations can be modulated using phase-locked closed-loop auditory stimulation in humans

REM sleep alpha and theta oscillations can be modulated using phase-locked closed-loop auditory stimulation in humans

Closed-loop auditory stimulation enhances total slow wave activity and proportionally shortens sleep duration in a young cohort

Closed-loop auditory stimulation enhances total slow wave activity and proportionally shortens sleep duration in a young cohort

The neurophysiology of closed-loop auditory stimulation in sleep: A magnetoencephalography study.

Closed-loop auditory stimulation (CLAS) is a brain modulation technique in which sounds are timed to enhance or disrupt endogenous neurophysiological events. CLAS of slow oscillation up-states in sleep is becoming a popular tool to study and enhance sleep's functions, as it increases slow oscillations, evokes sleep spindles and enhances memory consolidation of certain tasks. However, few studies have examined the specific neurophysiological mechanisms involved in CLAS, in part because of practical limitations to available tools. To evaluate evidence for possible models of how sound stimulation during brain up-states alters brain activity, we simultaneously recorded electro- and magnetoencephalography in human participants who received auditory stimulation across sleep stages. We conducted a series of analyses that test different models of pathways through which CLAS of slow oscillations may affect widespread neural activity that have been suggested in literature, using spatial information, timing and phase relationships in the source-localized magnetoencephalography data. The results suggest that auditory information reaches ventral frontal lobe areas via non-lemniscal pathways. From there, a slow oscillation is created and propagated. We demonstrate that while the state of excitability of tissue in auditory cortex and frontal ventral regions shows some synchrony with the electroencephalography (EEG)-recorded up-states that are commonly used for CLAS, it is the state of ventral frontal regions that is most critical for slow oscillation generation. Our findings advance models of how CLAS leads to enhancement of slow oscillations, sleep spindles and associated cognitive benefits and offer insight into how the effectiveness of brain stimulation techniques can be improved.

The effects of closed-loop auditory stimulation on sleep oscillatory dynamics in relation to motor procedural memory consolidation.

Healthy aging and many disorders show reduced sleep-dependent memory consolidation and corresponding alterations in non-rapid eye movement sleep oscillations. Yet sleep physiology remains a relatively neglected target for improving memory. We evaluated the effects of closed-loop auditory stimulation during sleep (CLASS) on slow oscillations (SOs), sleep spindles, and their coupling, all in relation to motor procedural memory consolidation. Twenty healthy young adults had two afternoon naps: one with auditory stimulation during SO upstates and another with no stimulation. Twelve returned for a third nap with stimulation at variable times in relation to SO upstates. In all sessions, participants trained on the motor sequence task prior to napping and were tested afterward. Relative to epochs with no stimulation, upstate stimuli disrupted sleep and evoked SOs, spindles, and SO-coupled spindles. Stimuli that successfully evoked oscillations were delivered closer to the peak of the SO upstate and when spindle power was lower than stimuli that failed to evoke oscillations. Across conditions, participants showed similar significant post-nap performance improvement that correlated with the density of SO-coupled spindles. Despite its strong effects on sleep physiology, CLASS failed to enhance motor procedural memory. Our findings suggest methods to overcome this failure, including better sound calibration to preserve sleep continuity and the use of real-time predictive algorithms to more precisely target SO upstates and to avoid disrupting endogenous SO-coupled spindles and their mnemonic function. They motivate continued development of CLASS as an intervention to manipulate sleep oscillatory dynamics and improve memory.

A system based on machine learning for improving sleep

Closed-loop auditory stimulation is one of the well-known and emerging sensory stimulation techniques, which achieves the purpose of sleep regulation by driving the EEG slow oscillation (SO, <1 Hz) through auditory stimulation. The main challenge is to accurately identify the stimulation timing and provide feedback in real-time, which has high requirements on the response time and recognition accuracy of the closed-loop auditory stimulation system. To reduce the impact of systematic errors on the regulation results, most traditional closed-loop auditory stimulation systems try to identify a single feature to determine the timing of stimulus delivery and reduce the system feedback delay by simplifying the calculation. Unlike existing closed-loop regulation systems that identify specific brain features, this paper proposes a closed-loop auditory stimulation sleep regulation system deploying machine learning. The process is: through online sleep real-time automatic staging, tracking the sleep stage to provide feedback quickly, and continuously offering external auditory stimulation at a specific SO phase. This paper uses this system to conduct sleep auditory stimulation regulation experiments on ten subjects. The experimental results show that the sleep closed-loop regulation system proposed in this paper can achieve consistency (effective for almost all subjects in the experiment) and immediate (taking effect immediately after stimulation) modulation effects on SOs. More importantly, the proposed method is superior to existing advanced methods. Therefore, the system designed in this paper has great potential to be more reliable and flexible in sleep regulation.

Closed-Loop Auditory Stimulation to Guide Respiration: Preliminary Study to Evaluate the Effect on Time Spent in Sleep Initiation during a Nap.

Various stimulation systems to modulate sleep structure and function have been introduced. However, studies on the time spent in sleep initiation (TSSI) are limited. This study proposes a closed-loop auditory stimulation (CLAS) to gradually modulate respiratory rhythm linked to the autonomic nervous system (ANS) activity directly associated with sleep. CLAS is continuously updated to reflect the individual's current respiratory frequency and pattern. Six participants took naps on different days with and without CLAS. The average values of the TSSI are 14.00 ± 4.24 and 9.67 ± 5.31 min in the control and stimulation experiments (p < 0.03), respectively. Further, the values of respiratory instability and heart rate variability differ significantly between the control and stimulation experiments. Based on our findings, CLAS supports the individuals to gradually modulate their respiratory rhythms to have similar characteristics observed near sleep initiation, and the changed respiratory rhythms influence ANS activities, possibly influencing sleep initiation. Our approach aims to modulate the respiratory rhythm, which can be controlled intentionally. Therefore, this method can probably be used for sleep initiation and daytime applications.

Feasibility, efficacy, and functional relevance of automated auditory closed-loop suppression of slow-wave sleep in humans.

Slow-wave sleep (SWS) is a fundamental physiological process, and its modulation is of interest for basic science and clinical applications. However, automatised protocols for the suppression of SWS are lacking. We describe the development of a novel protocol for the automated detection (based on the whole head topography of frontal slow waves) and suppression of SWS (through closed-loop modulated randomised pulsed noise), and assessed the feasibility, efficacy and functional relevance compared to sham stimulation in 15 healthy young adults in a repeated-measure sleep laboratory study. Auditory compared to sham stimulation resulted in a highly significant reduction of SWS by 30% without affecting total sleep time. The reduction of SWS was associated with an increase in lighter non-rapid eye movement sleep and a shift of slow-wave activity towards the end of the night, indicative of a homeostatic response and functional relevance. Still, cumulative slow-wave activity across the night was significantly reduced by 23%. Undisturbed sleep led to an evening to morning reduction of wake electroencephalographic theta activity, thought to reflect synaptic downscaling during SWS, while suppression of SWS inhibited this dissipation. We provide evidence for the feasibility, efficacy, and functional relevance of a novel fully automated protocol for SWS suppression based on auditory closed-loop stimulation. Future work is needed to further test for functional relevance and potential clinical applications.

Selective slow-wave sleep suppression through auditory closed-loop stimulation

Selective slow-wave sleep suppression through auditory closed-loop stimulation

Ongoing neural oscillations predict the post-stimulus outcome of closed loop auditory stimulation during slow-wave sleep

Large slow oscillations (SO, 0.5–2 Hz) characterise slow-wave sleep and are crucial to memory consolidation and other physiological functions. Manipulating slow oscillations may enhance sleep and memory, as well as benefitting the immune system. Closed-loop auditory stimulation (CLAS) has been demonstrated to increase the SO amplitude and to boost fast sleep spindle activity (11–16 Hz). Nevertheless, not all such stimuli are effective in evoking SOs, even when they are precisely phase locked. Here, we studied what factors of the ongoing activity patterns may help to determine what oscillations to stimulate to effectively enhance SOs or SO-locked spindle activity. Hence, we trained classifiers using the morphological characteristics of the ongoing SO, as measured by electroencephalography (EEG), to predict whether stimulation would lead to a benefit in terms of the resulting SO and spindle amplitude. Separate classifiers were trained using trials from spontaneous control and stimulated datasets, and we evaluated their performance by applying them to held-out data both within and across conditions. We were able to predict both when large SOs occurred spontaneously, and whether a phase-locked auditory click effectively enlarged them with good accuracy for predicting the SO trough (∼70%) and SO peak values (∼80%). Also, we were able to predict when stimulation would elicit spindle activity with an accuracy of ∼60%. Finally, we evaluate the importance of the various SO features used to make these predictions. Our results offer new insight into SO and spindle dynamics and may suggest techniques for developing future methods for online optimization of stimulation.

Auditory closed-loop stimulation on sleep slow oscillations using in-ear EEG sensors.

Acoustic stimulation synchronized to slow oscillations in scalp electroencephalograms has been shown to enhance sleep features, which makes it promising in boosting cognitive functions as well as in the treatment of some sleep disturbances. Nevertheless, scalp electrode sensors are resource intensive and poorly tolerated by sleeping patients. The aim of this study was to investigate the potential usability of in-the-ear electroencephalography to implement auditory closed-loop stimulation during sleep. For this, we evaluated the agreement between slow oscillation recordings obtained through the in-ear sensor and those obtained simultaneously from standard scalp electrodes during naps of 13 healthy subjects. We found that in-ear activity provided enough information to automatically detect sleep slow oscillations in real-time. Based on this, we successfully enhanced scalp slow oscillations using auditory single-cycle closed-loop brain-state-dependent stimulation based on in-ear signals acquired in 11 further subjects. We conclude that in-ear sensors provide a feasible technology for the enhancement of sleep patterns, and could pave the way for new clinical applications in the near future.

Just a sound: A non-pharmacological treatment approach in epilepsy

Benign epilepsy with centro-temporal spikes is typically not treated by antiepileptic drugs, but it leads to cognitive disfunctions. In this issue, Klinzing et al.1 demonstrate that closed-loop auditory stimulation delivered after paroxysmal spikes reduces the total number of paroxysmal spikes.

Auditory stimulation during sleep suppresses spike activity in benign epilepsy with centrotemporal spikes

SummaryBenign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy linked to diverse cognitive abnormalities. The electroencephalogram of patients shows focal interictal epileptic spikes, particularly during non-rapid eye movement (NonREM) sleep. Spike formation involves thalamocortical networks, which also contribute to the generation of sleep slow oscillations (SOs) and spindles. Motivated by evidence that SO-spindle activity can be controlled through closed-loop auditory stimulation, here, we show in seven patients that auditory stimulation also reduces spike rates in BECTS. Stimulation during NonREM sleep decreases spike rates, with most robust reductions when tones are presented 1.5 to 3.5 s after spikes. Stimulation further reduces the amplitude of spikes closely following tones. Sleep spindles are negatively correlated with spike rates, suggesting that tone-evoked spindle activity mediates the spike suppression. We hypothesize spindle-related refractoriness in thalamocortical circuits as a potential mechanism. Our results open an avenue for the non-pharmacological treatment of BECTS.

Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats.

Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves' phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down-phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single-pellet reaching task, respectively. Without affecting 24 hr sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. While up-phase CLAS does not elicit a significant change in behavioral performance, down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test. Overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe, and stable over chronic experimental periods, enabling the use of this high-specificity tool for basic and preclinical translational sleep research.

No benefit of auditory closed-loop stimulation on memory for semantically-incongruent associations

Auditory closed-loop stimulation has gained traction in recent years as a means of enhancing slow oscillatory activity and, consequently, sleep-associated memory consolidation. Previous studies on this topic have primarily focused on the consolidation of semantically-congruent associations. In this study, we investigated the effect of auditory closed-loop stimulation on the overnight retention of semantically-incongruent associations. Twelve healthy males (age: M = 20.06, SD = 2.02 years) participated in two experimental conditions (simulation and sham). In the stimulation condition, clicks were delivered in phase with slow oscillation up-states, whereas in the sham condition no auditory stimuli were applied. Corroborating earlier work, stimulation (vs. sham) enhanced the slow oscillation rhythm, phase-coupled spindle activity and slow oscillation power. However, there was no benefit of stimulation on overnight memory retention. These findings suggest that closed-loop stimulation does not benefit semantically-incongruent associations.

Evaluating Closed-loop Auditory Stimulation during Sleep as an Intervention to Improve Memory Consolidation (4149)

Evaluating Closed-loop Auditory Stimulation during Sleep as an Intervention to Improve Memory Consolidation (4149)