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Meissner, S. N.

Publications and source records attributed to Meissner, S. N..

6 recordsLinked to original sources

Video-based eye movements are linked to cortical and pupil-based arousal in human sleep

Study ObjectivesTo quantify high-resolution video-based eye kinematics across sleep macro- and microstructure and determine their coupling with pupil-based and cortical arousal markers. MethodsWe recorded polysomnography and utilized infrared video-based eye-tracking in 17 healthy adults. Computer vision was employed to extract eye position and speed, which were related to pupil size (subcortical arousal marker) and EEG spectral slope (cortical arousal marker) across sleep stages, rapid eye movement (REM) substates, and K-complexes. ResultsEye kinematics varied significantly across sleep stages (p<0.001), except for horizontal pupil position (p=0.192). Video-based eye position and speed are sufficient to classify stages with above chance level accuracy (47%). Eye movement speed positively correlated with pupil size during non-REM sleep (R[&ge;]0.21, p<0.001) and with spectral slope during wakefulness and REM sleep (R[&ge;]0.11, p<0.018). These strengths of the correlations differ depending on the direction of the eye movement. Phasic REM exhibited faster eye movements, larger pupil size (p<0.001), and a flatter spectral slope (p=0.014) compared to tonic REM, indicating elevated subcortical and cortical arousal. K-complexes were accompanied by increased eye movement speed (p<0.05) and a steeper spectral slope (p[&le;]0.010), suggesting a transient shift toward a sleep-protective cortical state despite concurrent oculomotor activation. ConclusionsVideo-based eye-tracking reveals that eye movements are quantitatively coupled to brain-wide arousal fluctuations in a state-dependent manner. This methodology provides a ground-truth framework for resolving fine-grained eye dynamics during sleep, offering a high-fidelity tool for sleep phenotyping and clinical assessment. Statement of significanceTraditional sleep monitoring relies on low-resolution electrical signals that often confound true eye movements with brain or muscle activity. This study uses high-resolution video tracking to establish a physical ground truth for eye kinematics across human sleep. We demonstrate that eye movements are coupled with both cortical and subcortical arousal levels in a state-dependent manner, providing a clearer neurophysiological distinction between, for example, sleep substates like tonic and phasic REM. This framework reveals how the eyes serve as a non-invasive window into the brains internal arousal state. Such insights address critical gaps in understanding sleep microarchitecture and offer a novel pathway for developing high-fidelity biomarkers for neurological disorders, such as Parkinsons disease, characterized by disrupted sleep-related arousal.

neuroscience↗

Reward Reduces Motor Fatigability by Increasing Movement Vigour

Reward can enhance motor performance. However, its potential to counteract motor fatigability, a reduction in motor performance during sustained movements, remains underinvestigated. This could be particularly relevant in neurological conditions such as multiple sclerosis, where increased motor fatigability is a prominent symptom. One form of motor fatigability is motor slowing, a decline in movement speed over time evoked by fast, repetitive movements. In this study, we investigated whether the possibility to earn reward attenuates motor slowing, and examined associated changes in muscle activity and pupil size, a putative marker of physical effort. Participants performed a wrist tapping task at maximal voluntary speed with or without the possibility of earning a reward. We found that wrist tapping induced motor slowing and that slowing was significantly reduced by reward. Over time, tapping became more costly as indicated by higher muscle activity and coactivation per tap. This was accompanied by a sustained pupil dilation, which could not solely be explained by tapping speed. These findings suggest that, rather than restoring efficient motor control, reward attenuates motor slowing by allowing participants to access a performance reserve and invest more resources into the task, reflected by increased muscle activation per tap and sustained pupil dilation.

neuroscience↗

Pupil self-regulation modulates markers of cortical excitability and cortical arousal

The brains arousal state (i.e., central arousal) is regulated by multiple neuromodulatory nuclei in the brainstem and significantly influences high-level cognitive processes. By exploiting the mechanistic connection between the locus coeruleus (LC), a key regulator of central arousal, and pupil dynamics, we recently demonstrated that participants can gain volitional control over arousal-regulating centers including the LC using a pupil-based biofeedback approach. Here, we test whether pupil-based biofeedback modulates electrophysiological markers of cortical excitability, cortical arousal, and phasic LC activity. Combining pupil-based biofeedback with single-pulse TMS, EEG recordings, and an auditory oddball task revealed three main results: pupil self-regulation significantly modulates (i) cortical excitability, (ii) the EEG spectral slope, a marker of cortical arousal, and (iii) the P300 response to target tones, an event-related potential suggested to be tightly linked to phasic LC activity. Interestingly, pupil self-regulation strength was linearly linked to the modulation of the spectral slope, suggesting a common physiological mechanism. Here, we have shown that pupil-based biofeedback modulates fundamental aspects of brain function. Whether this method could further be used to modulate these aspects in case of disturbances associated with neurological and psychiatric disorders needs to be investigated in future studies.

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Pupil size reveals arousal level dynamics in human sleep

Recent animal research has revealed the intricate dynamics of arousal levels that are potentially crucial for maintaining proper sleep resilience and memory consolidation. Also in humans, changes in arousal level are believed to be a determining characteristic of healthy and pathological sleep but tracking arousal fluctuations has been methodologically challenging. Here we measured pupil size, an established indicator of arousal levels, during overnight sleep and tested whether the arousal level affects cortical response to auditory stimulation. We show that pupil size dynamics change as a function of sleep macrostructure and microstructural events. In particular, pupil size is inversely related to the occurrence of sleep spindle clusters, a marker of sleep resilience. Additionally, pupil size prior to auditory stimulation influences the evoked response, most notably in delta power, a marker of several restorative and regenerative functions of sleep. Recording pupil size dynamics provides novel insights into the interplay between arousal levels and sleep oscillations, opening new avenues for future research and clinical applications in diagnosing and treating pathological sleep associated with abnormal arousal levels.

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Theta and alpha EEG oscillations reflect sleep need -- except during the wake maintenance zone

Increasing time spent awake results in accumulated sleep need, a process known as sleep homeostasis. Sleep homeostasis combines with a 24 h circadian rhythm to determine when and for how long we sleep. Both sleep homeostasis and the circadian rhythm substantially affect spectral power of the wake electroencephalogram (EEG), but not in ways predicted by current models. Specifically, these models hypothesize that time spent awake increases neuronal synaptic strength, which increases synchronization and should therefore increase oscillatory activity. However, the dominant wake EEG oscillations, measured as theta (4-8 Hz) and alpha power (8-12 Hz), do not follow the predicted buildup in homeostatic sleep pressure with time awake. This is due to a limitation of spectral power analysis, which does not distinguish between changes in the amplitude of oscillations from changes in the quantity of oscillations present in the signal. We wished to determine whether the amplitudes of EEG oscillations would specifically reflect homeostatic sleep pressure, independently from changes in quantity. We collected data from 18 young healthy adults during a 4-h sleep / 24-h extended wake paradigm. We indeed found that theta and alpha oscillation amplitudes reflect homeostatic sleep pressure, increasing along a saturating exponential function with time awake. Instead, theta quantities increased linearly with time awake, and alpha quantities decreased. Notably, theta and alpha amplitudes temporarily decreased during the wake maintenance zone (WMZ), a 3-4 h time window just before bedtime when it is difficult to fall asleep. Using pupillometry, we also found that mean pupil diameter increased during this window, while variance decreased. These results suggest that the WMZ is dependent on an alerting signal from the ascending arousal system. The WMZ therefore counteracts the observed build-up in homeostatic sleep pressure reflected in EEG amplitudes by temporarily desynchronizing cortical activity.

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Through the eye to the brain: Modulating LC-mediated arousal via pupil-based neurofeedback

The brains arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here, we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus (LC), one of the key regulators of central arousal, and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the LC and other brainstem structures involved in arousal control. Further, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brains arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioral and clinical applications across various domains, including stress-related and anxiety disorders.

neuroscience↗