Biology subjects

Fenzl, T.

Publications and source records attributed to Fenzl, T..

7 recordsLinked to original sources

bioRxiv2026

A single-channel EEG classification system for multiscale characterization of mouse vigilance state

Long-term analysis of mouse sleep is constrained by the dependence of conventional scoring on expert interpretation of electroencephalographic (EEG) and electromyographic (EMG) recordings. We developed a channel-agnostic, EEG-only framework that combines cross-animal sleep-stage classification, causal temporal organization, and probabilistic hypnodensity analysis from a single cortical EEG signal. Motor, somatosensory, and visual cortical recordings were treated independently by a convolutional-recurrent classifier, and generalization was evaluated using nested leave-one-mouse-out cross-validation in eight mice, with each test animal excluded from training, normalization, and model selection. The primary model achieved 0.897 {+/-} 0.058 accuracy and 0.856 {+/-} 0.076 macro-F1 across previously unseen animals while preserving the principal features of expert EEG/EMG-supported sleep architecture. Causal temporal smoothing reduced fragmented predictions and restored physiologically coherent episode durations, counts, and transition structure. Beyond categorical staging, the 4-s causal EEG window was advanced in 1-s steps to generate continuous Wake, NREM, and REM hypnodensity profiles. This representation preserved overall classification performance while revealing increased probability ambiguity and state mixing around expert-defined sleep transitions. The framework was subsequently deployed without supervised adaptation in six additional mice with 32-33 recorded days per animal, where it retained organized daily sleep architecture and probabilistic sleep structure over extended recordings while remaining sensitive to changes in recording conditions. Together, these results establish a single-channel EEG framework for robust cross-animal sleep staging, physiologically structured long-term analysis, and second-by-second characterization of sleep-state probabilities in mice.

neuroscience↗

bioRxiv2026

Characterizing Transition State in Mouse Vigilance with EEG-EMG Hypnodensity

Study ObjectivesVigilance-state transitions are continuous biological processes, yet conventional rodent sleep scoring relies on discrete epochs that obscure intermediate states. As no standardized framework exists for characterizing these intermediate states in rodents, this study aimed to characterize the temporal dynamics of transitions in mice and validate a machine-learning approach for objective detection. MethodsChronic EEG and EMG recordings were obtained from male C57BL/6N mice. We extracted 56-second windows containing stable transitions between Wakefulness (WAKE), Non-Rapid Eye Movement Sleep (NREMS), and Rapid Eye Movement Sleep (REMS). Eight trained experts manually annotated the onset and duration of transitions to establish ground truth and assess inter-rater reliability. Using quantitative EEG/EMG features (e.g., spectral power, complexity, EMG variance) derived from stable states, Support Vector Machine (SVM) classifiers were trained to predict transition midpoints in independent test animals. ResultsInter-rater agreement among experts was moderate to low, particularly for WAKE to NREMS and NREMS to REMS transitions, reflecting inherent ambiguity in manual scoring. Temporal analysis revealed distinct dynamics across transition types; NREMS to REMS transitions were significantly longer than all others, while REMS to NREMS transitions were the most abrupt. Despite the variability in human scoring, SVM models trained only on stable-state features successfully predicted expert-defined transition midpoints. ConclusionsOur approach not only characterized the recognizable dynamics across transition types in mice, but also provides a reproducible framework for quantifying sleep-wake transitions, which is crucial for studying arousal stability and related impairments in disease. Statement of SignificanceTraditional sleep scoring enforces discrete boundaries between vigilance states, overlooking transitional dynamics that may be critical for understanding arousal regulation. We developed a novel hypnodensity-based framework to systematically identify and characterize intermediate vigilance states in mice using EEG-EMG recordings. By combining expert annotations with machine learning, we revealed that transitions between sleep and wake involve continuous processes with mixed state features, rather than instantaneous switches. This approach provides the first standardized method for quantifying transitional vigilance states in rodents, enabling deeper investigation of arousal instability in neurological disorders. Our framework advances automated sleep analysis beyond classical three-state classification

neuroscience↗

bioRxiv2026

Pre-anaesthetic anxiety phenotype stratifies cortical excitability, learned navigation, and post-anaesthetic sleep in sevoflurane-exposed mice

Trait anxiety is a common pre-surgical phenotype and has been linked to adverse postoperative cognitive outcome, but whether it modulates the response to general anaesthesia has not been tested in a controlled design that isolates the anaesthetic from surgical injury. We classified 42 male C57BL/6N mice as low-anxiety (LA, n = 24) or high-anxiety (HA, n = 18) by unsupervised k-medoids clustering on cued fear-retrieval freezing, and exposed all animals to sevoflurane under live-EEG titration without surgery. At adequate anaesthetic depth, HA mice carried a flatter aperiodic (1/f) cortical slope than LA mice (AUC = 0.85, [0.70, 0.95]). Conventional water-cross-maze scoring returned null at post-anaesthetic re-test, but unsupervised decomposition of the same trial videos localised the effect to loss of a specific learned transition in HA mice (AUC = 0.72, [0.56, 0.86]). The dark-phase REMS response reversed direction, with HA mice losing REMS against their own baseline while LA mice gained it (AUC = 0.82, [0.65, 0.94]). The three effects are directionally consistent with modulation of cortical excitation-to-inhibition balance under sevoflurane. The aperiodic exponent and emergence-phase EEG trajectory, both recoverable from routine frontal EEG, are candidate pre-anaesthetic biomarkers.

neuroscience↗

bioRxiv2025

BACE1 regulates sleep-wake cycle through both enzymatic and non-enzymatic actions.

The {beta}-secretase BACE1 has become a prime target in Alzheimers disease (AD) therapy, because it drives the production of pathogenic amyloid {beta} peptides. However, clinical trials with BACE1-targeting drugs were halted due to adverse effects on cognitive performance. We propose here that cognitive impairment by BACE1 inhibitors may be a corollary of a higher function of BACE1 related to proper sleep regulation. To address non-enzymatic effects of BACE1 on ion channels likely involved in the sleep-wake cycle, we analyzed sleep patterns in both BACE1-KO mice and a newly generated transgenic line expressing a proteolysis-deficient BACE1 variant (BACE1-KI). We found that BACE1-KI and BACE1-KO mice displayed common and distinct sleep-wake disturbances. Compared to their respective wild-type littermates, both mutant lines slept less during the light phase (when they preferentially rest). Furthermore, transition rates between wake and sleep states were altered, as were sleep spindles and EEG power spectra mainly in the gamma range. Thus, a better understanding of how BACE1 interferes with sleep-modulated behaviors is needed if clinical trials with BACE1-targeted inhibitors are to resume.

animal behavior and cognition↗

bioRxiv2023

Nociception in chicken embryos, Part III: Analysis of movements before and after application of a noxious stimulus

Many potentially noxious interventions are performed on chicken embryos in research and in the poultry industry. It is therefore in the interest of animal welfare to define the point at which a chicken embryo is capable of nociception. The present part III of a comprehensive study examined the movements of developing chicken embryos with the aim of identifying behavioral responses to aww noxious stimulus. For this purpose, a noxious mechanical stimulus and a control stimulus were applied. The recorded movements of the embryos were evaluated using the markerless pose estimation software DeepLabCut and manual observations. After the application of the noxious stimulus, a significant increase in beak movement was identified in 15- to 18-day-old embryos. In younger embryos, no behavioral changes related to the noxious stimulus were observed. The results indicate that noxious stimuli at the beak base evoke a nocifensive reaction in chicken embryos starting at embryonic day 15.

animal behavior and cognition↗

bioRxiv2023

Nociception in chicken embryos, Part I: Analysis of cardiovascular responses to a mechanical noxious stimulus

While it is assumed that chicken embryos acquire the ability for nociception during the developmental period in the egg, an exact time point has not yet been specified. This study aimed to determine the onset of nociception during embryonic development in chicken. Changes in blood pressure and heart rate (HR) in response to a mechanical noxious stimulus at the base of the beak versus a light touch on the beak in chicken embryos between embryonic days (EDs) 7 and 18 were examined. Mean arterial pressure (MAP) was the most sensitive parameter for assessing cardiovascular responses. Significant changes in MAP in response to a noxious stimulus were detected in embryos at ED16 to ED18, while significant changes in HR were observed on ED17 and ED18. Infiltration anesthesia with the local anesthetic lidocaine significantly reduced reactions in MAP on ED18, so the cardiovascular changes can be assumed to be nociceptive responses.

physiology↗

bioRxiv2023

Nociception in chicken embryos, Part II: Embryonal development of electroencephalic neuronal activity in ovo as a prerequisite for nociception

Chicken culling is forbidden in Germany since 2022, male/female selection and male elimination must be brought to an embryonic status prior to the onset of nociception. The present study evaluated the ontogenetic point when noxious stimuli potentially could be perceived/processed in the brain in ovo. EEG-recordings from randomized hyperpallial brain sites were recorded in ovo and noxious stimuli were applied. Temporal and spectral analyses of the EEG were performed. The onset of physiological neuronal signals could be determined at developmental day 13. ERP/ERSP/ITC analysis did not reveal phase-locked nociceptive responses. Although no central nociceptive responses were documented, adequate EEG-responses to noxious stimuli from other brain areas cannot be excluded. The extreme stress impact on the embryo during the recording may overwrite the perception of noniceptive stimuli. The results suggest developmental day 13 as the earliest embryonal stage being able to receive and process nociceptive stimuli.

neuroscience↗