Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults.

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.

'High-Density-SleepCleaner': An open-source, semi-automatic artifact removal routine tailored to high-density sleep EEG.

BACKGROUND: With up to 256 channels, high-density electroencephalography (hd-EEG) has become essential to the sleep research field. The vast amount of data resulting from this magnitude of channels in overnight EEG recordings complicates the removal of artifacts. NEW METHOD: We present a new, semi-automatic artifact removal routine specifically designed for sleep hd-EEG recordings. By employing a graphical user interface (GUI), the user assesses epochs in regard to four sleep quality markers (SQMs). Based on their topography and underlying EEG signal, the user eventually removes artifactual values. To identify artifacts, the user is required to have basic knowledge of the typical (patho-)physiological EEG they are interested in, as well as artifactual EEG. The final output consists of a binary matrix (channels x epochs). Channels affected by artifacts can be restored in afflicted epochs using epoch-wise interpolation, a function included in the online repository. RESULTS: The routine was applied in 54 overnight sleep hd-EEG recordings. The proportion of bad epochs highly depends on the number of channels required to be artifact-free. Between 95% and 100% of bad epochs could be restored using epoch-wise interpolation. We furthermore present a detailed examination of two extreme cases (with few and many artifacts). For both nights, the topography and cyclic pattern of delta power look as expected after artifact removal. COMPARISON WITH EXISTING METHODS: Numerous artifact removal methods exist, yet their scope of application usually targets short wake EEG recordings. The proposed routine provides a transparent, practical, and efficient approach to identify artifacts in overnight sleep hd-EEG recordings. CONCLUSION: This method reliably identifies artifacts simultaneously in all channels and epochs.

Neuromodulation by means of phase-locked auditory stimulation affects key marker of excitability and connectivity during sleep.

The propagating pattern of sleep slow waves (high-amplitude oscillations < 4.5 Hz) serves as a blueprint of cortical excitability and brain connectivity. Phase-locked auditory stimulation is a promising tool for the modulation of ongoing brain activity during sleep; however, its underlying mechanisms remain unknown. Here, eighteen healthy young adults were measured with high-density electroencephalography in three experimental conditions; one with no stimulation, one with up- and one with down-phase stimulation; ten participants were included in the analysis. We show that up-phase auditory stimulation on a right prefrontal area locally enhances cortical involvement and promotes traveling by increasing the propagating distance and duration of targeted small-amplitude waves. On the contrary, down-phase stimulation proves more efficient at perturbing large-amplitude waves and interferes with ongoing traveling by disengaging cortical regions and interrupting high synchronicity in the target area as indicated by increased traveling speed. These results point out different underlying mechanisms mediating the effects of up- and down-phase stimulation and highlight the strength of traveling wave analysis as a sensitive and informative method for the study of connectivity and cortical excitability alterations.

Boosting Recovery During Sleep by Means of Auditory Stimulation.

Sufficient recovery during sleep is the basis of physical and psychological well-being. Understanding the physiological mechanisms underlying this restorative function is essential for developing novel approaches to promote recovery during sleep. Phase-targeted auditory stimulation (PTAS) is an increasingly popular technique for boosting the key electrophysiological marker of recovery during sleep, slow-wave activity (SWA, 1-4 Hz EEG power). However, it is unknown whether PTAS induces physiological sleep. In this study, we demonstrate that, when applied during deep sleep, PTAS accelerates SWA decline across the night which is associated with an overnight improvement in attentional performance. Thus, we provide evidence that PTAS enhances physiological sleep and demonstrate under which conditions this occurs most efficiently. These findings will be important for future translation into clinical populations suffering from insufficient recovery during sleep.

Sleep electroencephalographic asymmetry in Parkinson's disease patients before and after deep brain stimulation.

OBJECTIVE: Unilateral manifestation of motor dysfunction is a prominent hallmark of Parkinson's disease (PD). We investigated how the motor laterality of the disorder affects sleep neural asymmetry before and after Deep Brain Stimulation (DBS). METHODS: Twenty-seven PD patients of the akinetic-rigid subtype were studied; 11 with right dominant (RD) and 16 with left dominant (LD) motor symptoms. Neuronal sleep asymmetry was computed as the difference of sleep slow-wave energy (SWE) between left and right hemispheres. We used linear mixed models to assess the relationship between symptomatic profile and SWE asymmetry. RESULTS: LD PD patients exhibited frontal electroencephalographic (EEG) asymmetry and motor laterality pre-DBS with increased SWE contralateral to their affected body side, which diminished post-DBS. The RD group did not exhibit neither neural asymmetry nor motor laterality pre- and post-DBS. There was a significant negative correlation between the motor laterality and sleep EEG asymmetry. CONCLUSIONS: Our results suggest evidence for a local use-dependent modulation of SWE as a result of the lateralized pathological motor profile. More bilateral motor symptoms and optimized treatment contribute to diminished sleep EEG asymmetry. SIGNIFICANCE: These novel findings about the association between symptomatic motor laterality and sleep neural asymmetry may provide targeted therapeutic insights.

Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep.

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.