Biology subjects

Karlen, W.

Publications and source records attributed to Karlen, W..

6 recordsLinked to original sources

bioRxiv2025

Local modulation of sleep slow waves depends on timing between auditory stimuli

Conflicting evidence exists regarding the role of the targeted slow-wave phase in determining the direction and spatial specificity of slow-wave activity (SWA) modulation via phase-targeted auditory stimulation (PTAS) during sleep. To reconcile these discrepancies, we re-analyzed high-density electroencephalography (hd-EEG) data from previous studies, focusing on SWA responses to auditory stimuli presented with varying inter-stimulus intervals (ISIs). Our analysis reveals that ISI is a primary determinant of PTAS-induced SWA modulation, exceeding the influence of targeted phase alone. Specifically, auditory stimulation with longer ISIs evoked a global increase in SWA, consistent with a stereotypical auditory-evoked K-complex (KC), independent of targeted phase. Conversely, longer stimulus trains with rapid successive stimulus presentation resulted in spatially localized, phase-dependent SWA modulation, with up-PTAS enhancing and down-PTAS reducing SWA locally around the targeted area. This distinction resolves inconsistencies in prior PTAS studies by demonstrating that phase alone in insufficient in predicting slow-wave responses. Rather, it was the ISI which determined whether PTAS resulted in a global, KC-mediated response or a local, phase-specific modulation of SWA. Consequently, our findings refine the mechanistic understanding of PTAS, suggesting that ISI regulates the engagement of distinct neural circuits and thereby potentially enables the targeted manipulation of specific slow-wave subtypes and their associated functions.

neuroscience↗

bioRxiv2024

Longer Interstimulus Intervals Enhance Efficacy of Automated Phase-Targeted Auditory Stimulation on Procedural Memory Consolidation

Up-phase-targeted auditory stimulation (up-PTAS) during slow-wave sleep has become a valuable tool for modulating slow oscillations and slow-oscillation-spindle-coupling in favor of overnight memory retention. Developing effective, automated protocols for translation into more naturalistic or clinical settings is an ongoing challenge, especially given that current PTAS protocols and their behavioral effects vary greatly between different studies. Here, we assessed the electrophysiological and behavioral effects of systematically varying interstimulus intervals (ISIs) in automated up-PTAS in the home setting, using a mobile PTAS device and app-based behavioral tasks. Building on studies suggesting a non-linear relationship between stimulus number and PTAS effects, we show that applying fewer stimuli with longer ISIs enhanced overnight memory consolidation of a finger-tapping sequence more effectively than applying more stimuli with shorter ISIs. The behavioral response was predicted by the number of stimuli with auditory evoked K-complexes relative to the number of stimuli without K-complexes. PTAS stimuli applied at longer ISIs (> 1.25) were associated with a higher likelihood of K-complex responses and fast spindles nesting in the K-complex up-phase. Our results suggest that up-PTAS can be optimized for overnight memory consolidation by introducing ISIs of at least 1.25s. Our study highlights the feasibility of longitudinal at-home PTAS combined with app-based behavioral tasks in healthy participants while leveraging the mechanistic insights such data can offer. Statement of SignificancePhase-targeted auditory stimulation (PTAS) holds great promise for non-invasively enhancing essential functions of slow-wave sleep. However, current protocols have produced variable results and are often confined to laboratory settings. Our study demonstrates the feasibility of a mobile application of automated PTAS and provides experimental evidence that prolonging interstimulus intervals positively affects overnight procedural memory consolidation via K-complexes and coupled sleep spindles. As K-complexes may also be involved in cardiovascular function and brain waste clearance, the proposed protocol optimization may have effects beyond memory enhancement. Together, our findings lay a foundation for a broader application of PTAS in clinical longitudinal studies to improve patient care and recovery outcomes.

neuroscience↗

bioRxiv2023

Acoustically evoked K-complexes are sufficient to boost verbal memory consolidation during sleep

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.

neuroscience↗

bioRxiv2021

Get rid of the beat in mobile EEG applications: A framework towards automated cardiogenic artifact detection and removal in single-channel EEG

Brain activity recordings outside clinical or laboratory settings using mobile EEG systems have recently gained popular interest allowing for realistic long-term monitoring and eventually leading to identification of possible biomarkers for diseases. The less obtrusive, minimized systems (e.g. single-channel EEG, no ECG reference) have the drawback of artifact contamination with varying intensity that are particularly difficult to identify and remove. We developed brMEGA, the first algorithm for automated detection and removal of cardiogenic artifacts using non-linear time-frequency analysis and machine learning to (1) detect whether and where cardiogenic artifacts exist, and (2) remove those artifacts. We compare our algorithm against visual artifact identification and a previously established approach and validate it in one real and semi-real datasets. We demonstrated that brMEGA successfully identifies and substantially removes cardiogenic artifacts in single-channel EEG recordings. Moreover, recovery of cardiogenic artifacts gives the opportunity for future extraction of heart rate features without ECG measurement.

neuroscience↗

bioRxiv2018

The saturation gap: a simple transformation of oxygen saturation using virtual shunt

ObjectivePeripheral oxygen saturation (SpO2) obtained from pulse oximetry is a widely used physiological measurement. Clinical interpretation is limited by the nonlinear relationship between SpO2, degree of impairment in gas exchange, and effect of altitude. SpO2 is frequently dichotomized to overcome these limitations during prediction modelling. Using the known physiological relationship between virtual shunt and SpO2, we propose the saturation gap as a transformation of SpO2.\n\nApproachWe computed the theoretical virtual shunt corresponding to various SpO2 values and derived an accurate approximation formula between virtual shunt and SpO2. The approximation was based on previously described empiric observations and known physiological relationships. We evaluated the utility of the saturation gap in a clinical study predicting the need for facility admission in children in a rural health-care setting.\n\nMain ResultsThe transformation was saturation gap = 49.314*log10(103.711 - SpO2) -37.315. The ability to predict hospital admission based on a continuous variable SpO2 or saturation gap produced an identical area under the curve of 0.71 (95% CI: 0.69-0.73), compared to only 0.57 (CI: 0.56-0.58) based on diagnosis of hypoxemia (defined as SpO2<90%). However, SpO2 demonstrated a lack of fit compared to saturation gap (goodness-of-fit test p-value <0.0001 versus 0.098). The observed admission rates varied linearly with saturation gap but varied nonlinearly with SpO2.\n\nSignificanceThe saturation gap estimates a continuous linearly interpretable disease severity from SpO2 and improves clinical prediction models. The saturation gap will also allow for straightforward incorporation of altitude in interpretation of measurements of SpO2.

bioengineering↗

bioRxiv2018

Physiologically driven, altitude-adaptive model for the interpretation of pediatric oxygen saturation at altitudes above 2000 m a.s.l.

Measuring peripheral oxygen saturation (SpO2) with pulse oximeters at the point of care is widely established. However, since SpO2 is dependent on ambient atmospheric pressure, the distribution of SpO2 values in populations living above 2000 m a.s.l. is largely unknown. Here, we propose and evaluate a computer model to predict SpO2 values for pediatric permanent residents living between 0 and 4000 m a.s.l. Based on a sensitivity analysis of oxygen transport parameters, we created an altitude-adaptive SpO2 model that takes physiological adaptation of permanent residents into account. From this model, we derived an altitude-adaptive abnormal SpO2 threshold using patient parameters from literature. We compared the obtained model and threshold against a previously proposed threshold derived statistically from data and two empirical datasets independently recorded from Peruvian children living at altitudes up to 4100 m a.s.l. Our model followed the trends of empirical data, with the empirical data having a narrower healthy SpO2 range below 2000 m a.s.l., but the medians did never differ more than 2.29% across all altitudes. Our threshold estimated abnormal SpO2 in only 17 out of 5981 (0.3%) healthy recordings, whereas the statistical threshold returned 95 (1.6%) recordings outside the healthy range. The strength of our parametrised model is that it is rooted in physiology-derived equations and enables customisation. Furthermore, as it provides a reference SpO2, it could assist practitioners in interpreting SpO2 values for diagnosis, prognosis, and oxygen administration at higher altitudes.\n\nNew & NoteworthyOur model describes the altitude-dependent decrease of SpO2 in healthy pediatric residents based on physiological equations and can be adapted based on measureable clinical parameters. The proposed altitude-specific abnormal SpO2 threshold might be more appropriate than rigid guidelines for administering oxygen that currently are only available for sea level patients. We see this as a starting point to discuss and adapt oxygen administration guidelines.

physiology↗