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Kayser, C.

Publications and source records attributed to Kayser, C..

At least 19 recordsLinked to original sources

Spontaneous Perceptual Reversals reflect in Internal Rhythms, Not Metabolic Shifts or Evoked Responses

The perceptual interpretation of a static image, such as the Necker cube, can change spontaneously, resulting in endogenously driven changes in perception. We studied how different peripheral markers of the bodys physiological state, as well as time-resolved markers of EEG-derived brain activity, modulate around such spontaneous changes in perception. Specifically, we quantified the time course of heart rate, respiration rate, respiration phase, pupil size, EEG evoked responses, and EEG time-frequency activity around spontaneous perceptual reversals, and tested how these signals differ between the two interpretations of the Necker cube. Our results show that signals relating to the bodys and brains momentary state differ between the two perceptual interpretations, including pupil size, respiration phase, and rhythmic EEG activity. In contrast, signals relating to metabolic state or external stimuli, including respiration rate, heart rate and EEG evoked responses, did not differ between perceptual interpretations, but were consistently modulated around these. This corroborates the notion that spontaneous changes in perception are related to specific and coordinated windows in the cardiorespiratory cycle and neural markers of arousal or top-down processing. These windows are differentially expressed across interacting physiological systems, highlighting the intricate link between perception, brain activity and bodily physiology.

neuroscience↗

L1CAMxCD3 bispecific antibodies exert potent anti-tumor effects in preclinical pancreatic cancer models with representation of the complex tumor microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) with pancreatic myofibroblasts (PMF) and macrophages being two prominent cell populations essentially impairing tumor responses to (immuno)therapies. L1 cell adhesion molecule (L1CAM) is upregulated in PDAC cells in primary and metastatic tissues and associated with tumor progression and therapy resistance. Using L1CAM as tumor-associated antigen, two bispecific antibodies (bsAB) targeting L1CAM and CD3 were developed in the IgG-(L)-ScFv format and their anti-tumorigenic activity was investigated in different preclinical PDAC models. In 2D models, both L1-bsAB exerted L1CAM-specific anti-PDAC cell activity when co-cultured with activated CD8+ T cells. Strong anti-PDAC cell effects along with elevated release of T cell effector molecules were also observed upon co-culture with peripheral blood mononuclear cells (PMBC) from healthy donors and PDAC patients. Of note, both L1-bsAB were also effective in 3D PDAC cell spheroids and neither impaired by PMF nor macrophages. Finally, application of L1-bsAB on organotypic tissue slice cultures from PDAC tissues comprising the entire complex TME also induced PDAC cell apoptosis and release of T cell effector molecules. Overall, our results highlight relevant anti-PDAC cell activity of L1-bsAB in immunosuppressive contexts supporting their potential as immunotherapeutic strategy for PDAC.

cancer biology↗

Stability of Eye Movement-Related Eardrum Oscillations to acoustic and gravitational manipulations

Recent studies describe Eye Movement-Related Eardrum Oscillations (EMREOs), low-frequency signals recorded in the ear canal that arise from the tympanic membrane and are triggered by saccadic eye movements. Because EMREOs are thought to arise from motor elements in the peripheral auditory system, we examined how two known modulators of these elements affect the EMREO time course. First, the activity of outer hair cells (OHC) can be suppressed by the medial olivocochlear reflex (MOCR). If OHCs contribute to the generation of EMREOs, activation of this reflex should reduce EMREO amplitude. To test this, we compared EMREO amplitudes elicited by saccades performed in silence and in the presence of contralateral noise. Second, postural (i.e. vestibular and proprioceptive) cues linked to head orientation may influence EMREOs via oculomotor control circuits that possibly modulate middle ear muscles. To test this, we recorded EMREOs while participants made saccades with their head upright (0{degrees} azimuth) and with their head tilted 30{degrees} in either direction. Across both experiments our data reveal no clear modulation of the EMREO time course by these experimental manipulations. Together with other recent studies these findings advocate for a stability of the EMREO time course towards multiple experimental modulations and fuel speculations that the signal may serve as a temporal reference frame rather than a spatial coordinate transform function when combining signals across the senses.

neuroscience↗

Spontaneous perceptual reversals are accompanied by systematic changes in pupil size but not respiration phase

Humans tend to align their respiration with important events, in line with the notion that respiration serves as a tool to allocate (neuro-)physiological resources. This respiration alignment is consistently reported in laboratory studies relying on sequences of stimulus-driven experimental trials. However, whether such respiration alignment also occurs in the absence of external cues - such as during spontaneous perceptual changes - remains unknown. However, pupil size is known to change around spontaneous changes in perception, and pupil size supposedly covaries with respiration phase, suggesting that indeed respiration may align to spontaneous changes in perception. We investigate the link between respiration, pupil size, and spontaneous perceptual changes while participants (n=21) reported spontaneous perceptual reversals while viewing an ambiguous Necker cube. We confirmed the biphasic modulation of pupil size around reversals (constriction followed by dilation) and the general variation of pupil size with respiration phase. However, this coupling of pupil size and respiration phase broke down around perceptual reversals. Crucially, our data reveal no clear alignment of respiration phase to perceptual reversals although respiration frequency was predictive of the perceptual stability duration. These findings suggest that the temporal predictability of external events is critical for the robust respiration alignment to cognitive events.

neuroscience↗

Effects of Short-Term Breathwork on Respiration and Cognition

Respiration is a unique physiological process that can operate automatically but can also be deliberately used to modulate the bodily state. Importantly, respiration is deeply intertwined with neural processes, influencing processes from arousal and attention to executive control. Although structured respiration (breathing practice) has been exploited for centuries, the immediate consequences of short periods of structured respiration for sensation and cognition remain poorly understood. The present study examined how brief, one-minute episodes of structured respiration affect respiration and performance in a subsequent sensory-cognitive task. Across two experiments, participants engaged in structured breathing practices manipulating either respiratory frequency (slow breathing vs. fast breathing) or the inhalation-exhalation ratio (short inspiration-long expiration; long inspiration-short expiration) prior to performing a visual emotion discrimination task. Immediately after breathing practice, participants respiration deviated from their baseline: each technique resulted in specific deviations of respiratory frequency, inhalation-exhalation ratio, or the occurrence of atypical respiratory cycles, suggesting technique-specific returns to regular respiration. During the subsequent emotion response accuracy or reaction times did not differ between breathing practices. However, we observed transient improvements in reaction times immediately following all practices, suggesting a brief facilitation of attentional or sensorimotor responsiveness following conscious breathing. Our findings indicate that even brief, consciously controlled respiration can transiently influence cognitive performance, highlighting the role of voluntary respiratory modulation in shaping brain function and behavior.

animal behavior and cognition↗

Eye Movement-Related Eardrum Oscillations (EMREOs) Do Not Have a Direct Impact on Auditory Spatial Discrimination

Eye-movement-related eardrum oscillations (EMREOs) are pressure changes recorded in the ear that supposedly reflect displacements of the tympanic membrane induced by saccadic eye movements. Previous studies hypothesized that the underlying mechanisms might play a role in combining visual and acoustic spatial information. Yet, whether and how the eardrum moves during an EMREO and whether this movement affects acoustic spatial perception remains unclear. We here probed human acoustic lateralization performance for sounds presented at different times during a saccade (hence the EMREO) in two tasks, one relying on free-field sounds and one presenting sounds in-ear. Since the EMREO generation likely involves the middle ear muscles, whose tension can alter sound transmission, it is possible that judgements of sound locations may vary with the state of the ERMEO at the time of sound presentation. However, when testing two specific hypotheses of how movements of the eardrum underlying the EMREO may affect spatial hearing, we found no evidence in support of this. Still, and in line with previous studies, we found that participants lateralization responses were shaped by the spatial congruency of the saccade target direction and the sound direction. Thus, either the eardrum does not move directly as reflected by the EMREO signal, or despite its movement the underlying changes at the tympanic membrane only have minimal perceptual impact. Our results call for more refined studies to understand how the eardrum moves during a saccade and whether or how the EMREO impacts spatial perception.

neuroscience↗

The alignment of respiration to sensory-motor events is shaped by expected effort.

Humans often align their respiration with external events, a phenomenon thought to optimize neural resources for perception and action. Indeed, in sensory-cognitive experiments participants tend to align their respiration to the upcoming expected trials and their respiratory phase relates to neurophysiological processes reflecting changes in neural excitation, attention or arousal. However, it remains unclear whether this alignment is a passive entrainment to a tasks overall rhythm or an active process selectively aligning respiration based on the demands of individual events. We here tested this by recording respiration during three visual discrimination experiments that manipulated trial importance by either imposing different response deadlines or by manipulating trial value and difficulty. Our results show that participants align their respiration more consistently around stimulus onset for trials with short deadlines or trials presenting high-value and high-difficulty. These findings demonstrate that respiratory alignment is dynamically modulated on a trial-by-trial basis according to the anticipated required effort or task demands. Hence we conclude that respiration serves as an active tool to strategically allocate cognitive resources for sensory-motor challenges.

neuroscience↗

Evidence for systematic - yet task- and motor-contingent - rhythmicity of auditory perceptual judgements

Numerous studies advocate for a rhythmic mode of perception. However, the evidence in the context of auditory perception remains inconsistent. We propose that the divergent conclusions drawn from previous work stem from conceptual and methodological issues. These include ambiguous assumptions regarding the origin of perceptual rhythmicity, variations in listening tasks and attentional demands, differing analytical approaches, and the reliance on fixed participant samples for statistical testing. To systematically address these points, we conducted a series of experiments in which human participants performed auditory tasks involving monaural target sounds presented against binaural white noise backgrounds, while also recording eye movements. These experiments varied in whether stimuli were presented randomly or required motor initialization by the participants, the necessity of memory across trials and the manipulation of attentional demands across modalities. Our findings challenge the notion of universal rhythmicity in hearing, but support the existence of paradigm- and ear-specific fluctuations in perceptual sensitivity and response bias that emerge at multiple frequencies. Notably, the rhythmicity for sounds in the left and right ears appears to be largely independent among participants, and the strength of rhythmicity in behavioural data is possibly linked to oculomotor activity and attentional requirements of the task. Overall, these results may help to resolve conflicting conclusions drawn in previous work and provide specific avenues for further studies into the rhythmicity of auditory perception.

neuroscience↗

The respiratory phase modulates task-related neural representations of visual stimuli

We investigate how respiration influences cognition by examining the interaction between respiratory phase and task-related brain activity during two visual categorization tasks. While prior research shows that cognitive performance varies along the respiratory cycle, the underlying neurophysiological mechanisms remain poorly understood. Though some studies have shown that large-scale neural activity reflecting changes in the excitation-inhibition balance is co-modulated with the respiratory cycle, it remains unclear whether respiration directly shapes the quality by which task-relevant sensory information is encoded. We address this gap by applying single-trial multivariate analyses to EEG data obtained in humans, allowing us to track how respiration modulates the sensory evidence in this neurophysiological signal. Confirming previous studies, our data show that participants performance varies with the respiratory phase prior and during a trial. Importantly, they also suggest that respiration directly influences the sensory evidence carried by parieto-occipital processes emerging around 300 to 200 ms prior to participants responses. Hence, respiration and sensory-cognitive processes are not only highly intertwined but respiration directly facilitates the representation of behaviourally-relevant signals in the brain.

neuroscience↗

Unraveling eye movement-related eardrum oscillations (EMREOs): how saccade direction and middle ear properties shape amplitude and time course

Eye movement-related eardrum oscillations (EMREOs) reflect movements of the tympanic membrane that scale with the magnitude and direction of saccades. EMREOs have been consistently described in humans and non-human primates, yet many questions regarding this phenomenon remain unresolved. Based on bilateral in-ear recordings in human participants we here explore several properties of these EMREOs in order to improve our understanding of this signals origin and functional significance. Our data support that the EMREO time course is comparable between the left and right ears, and between paradigms guiding saccades by visual and auditory target stimuli. However, the precise amplitude time course differs significantly between ipsi-and contralateral saccades in addition to the previously known phase-inversion described for saccades in opposing directions. Finally, our data suggest that the EMREO amplitude is negatively related to the compliance of the tympanic membrane as established by tympanometry. Collectively, these results support the notion that EMREOs reflect motor-related top-down signals relayed to the ear from yet-to-be-resolved sources, and fuel the speculation that EMREOs may be generated by the middle ear muscles in a differential operation similar to the execution of ipsi-and contralateral saccades.

neuroscience↗

Respiration shapes response speed and accuracy with a systematic time lag

Sensory-cognitive functions are intertwined with physiological processes such as the heart beat or respiration. For example, we tend to align our respiratory cycle to expected events or actions. This happens during sports but also in computer-based tasks and systematically structures respiratory phase around relevant events. However, studies also show that trial-by-trial variations in respiratory phase shape brain activity and the speed or accuracy of individual responses. We show that both phenomena, the alignment of respiration to expected events and the explanatory power of the respiratory phase on behaviour co-exist. In fact, both the average respiratory phase of an individual relative to the experimental trials and trial-to-trial variations in respiratory phase hold significant predictive power on behavioural performance, in particular for reaction times. This co-modulation of respiration and behaviour emerges regardless of whether an individual generally breathes faster or slower and is strongest for the respiratory phase about two seconds prior to participants responses. The persistence of these effects across 12 datasets with 277 participants performing sensory-cognitive tasks confirm the robustness of these results, and suggest a profound and time-lagged influence of structured respiration on sensory-motor responses.

neuroscience↗

Perceived multisensory common cause relations shape the ventriloquism effect but only marginally the trial-wise aftereffect

Combining multisensory cues is fundamental for perception and action, and reflected by two frequently-studied phenomena: multisensory integration and sensory recalibration. In the context of audio-visual spatial signals, these are exemplified by the ventriloquism effect and its aftereffect. The ventriloquism effect occurs when the perceived location of a sound is biased by a concurrent visual stimulus, while the aftereffect manifests as a recalibration of sound localization after exposure to spatially discrepant stimuli. The relationship between these processes--whether recalibration is a direct consequence of integration or operates independently--remains debated. This study investigates the role of causal inference in these processes by examining whether trial-wise judgments of audio-visual stimuli as originating from a common cause influence both the ventriloquism effect and the immediate aftereffect. Using a spatial paradigm, participants made explicit judgments about the common cause of stimulus pairs, and their influence on both perceptual biases was assessed. Our results indicate that while multisensory integration is contingent on common cause judgments, the immediate recalibration effect is not. This suggests that recalibration can occur independently of the perceived commonality of the multisensory stimuli, challenging the notion that recalibration is solely a byproduct of integration.

neuroscience↗

Dissociating endogenous and exogenous delta activity during natural speech comprehension

Decoding human speech requires the brain to segment the incoming acoustic signal into meaningful linguistic units, ranging from syllables and words to phrases. Integrating these linguistic constituents into a coherent percept sets the root of compositional meaning and hence understanding. One important cue for segmentation in natural speech are prosodic cues, such as pauses, but their interplay with higher-level linguistic processing is still unknown. Here we dissociate the neural tracking of prosodic pauses from the segmentation of multi-word chunks using magnetoencephalography (MEG). We find that manipulating the regularity of pauses disrupts slow speech-brain tracking bilaterally in auditory areas (below 2 Hz) and in turn increases left-lateralized coherence of higher frequency auditory activity at speech onsets (around 25 - 45 Hz). Critically, we also find that multi-word chunks--defined as short, coherent bundles of inter-word dependencies--are processed through the rhythmic fluctuations of low frequency activity (below 2 Hz) bilaterally and independently of prosodic cues. Importantly, low-frequency alignment at chunk onsets increases the accuracy of an encoding model in bilateral auditory and frontal areas, while controlling for the effect of acoustics. Our findings provide novel insights into the neural basis of speech perception, demonstrating that both acoustic features (prosodic cues) and abstract processing at the multi-word timescale are underpinned independently by low-frequency electrophysiological brain activity.

neuroscience↗

Stimulus specific and configurational features of multiple visual stimuli shape multisensory binding

Studies on multisensory perception often focus on simplistic conditions in which one single stimulus is presented per modality. Yet, in everyday life we usually encounter multiple signals per modality. To understand how multiple signals within and across the senses are combined we extended the classical audio-visual spatial ventriloquism paradigm to combine two visual stimuli with one sound. The individual visual stimuli presented in the same trial differed in their relative timing and spatial offsets to the sound, allowing us to contrast their individual and combined influence on sound localization judgements. We find that the ventriloquism bias is not dominated by a single visual stimulus but rather is shaped by the collective multisensory evidence. In particular, the contribution of an individual visual stimulus to the ventriloquism bias depends not only on its own relative spatio-temporal alignment to the sound but also the spatio-temporal alignment of the other visual stimulus. We propose that this pattern of multi-stimulus multisensory integration reflects the evolution of evidence for sensory causal relations during individual trials, calling for the need to extend established models of multisensory causal inference to more naturalistic conditions. Our data also suggest that this pattern of multisensory interactions extends to the ventriloquism aftereffect, a bias in sound localization observed in unisensory judgements following a multisensory stimulus.

neuroscience↗

Detection of spatially-localized sounds is robust to saccades and concurrent eye movement-related eardrum oscillations (EMREOs)

Hearing is an active process and recent studies show that even the ear is affected by cognitive states or motor actions. One example are movements of the eardrum induced by saccadic eye movements - known as "eye movement-related eardrum oscillations" (EMREOs). While these are systematically shaped by the direction and size of saccades, the consequences of saccadic eye movements and their resulting EMREOs for hearing remain unclear. We here studied their implications for the detection of near-threshold clicks in human participants. Across three experiments sound detection was not affected by their time of presentation relative to saccade onset, by saccade amplitude or direction. While the EMREOs were shaped by the direction and amplitude of the saccadic movement, inducing covert shifts in spatial attention did not affect the EMREO, suggesting that this signature of active sensing is restricted to overt changes in visual focus. Importantly, in our experiments fluctuations in the EMREO amplitude were not related to detection performance, at least when monaural cues are sufficient. Hence while eye movements may shape the transduction of acoustic information the behavioral implications remain unclear.

neuroscience↗

Different time scales of common-cause evidence shape multisensory integration, recalibration and motor adaptation

Perception engages the processes of integration, recalibration and sometimes motor adaptation to deal with discrepant multisensory stimuli. These processes supposedly deal with sensory discrepancies on different time scales, with integration reducing immediate ones and recalibration and motor adaptation reflecting the cumulative influence of their recent history. Importantly, whether discrepant signals are bound during perception is guided by the brains inference of whether they originate from a common cause. When combined, these two notions lead to the hypothesis that the different time scales on which integration and recalibration (or motor adaptation) operate are associated with different time scales of evidence of a common cause underlying two signals. We tested this prediction in a well-established visuo-motor paradigm, in which human participants performed visually guided hand movements. The kinematic correlation between hand and cursor movements indicates their common origin, allowing us to manipulate the common-cause evidence by this correlation between visual and proprioceptive signals. Specifically, we dissociated hand and cursor signals during individual movements while preserving their correlation across movement endpoints. Following our hypothesis, this manipulation reduced integration compared to a condition in which visual and proprioceptive signals were perfectly correlated. In contrast, recalibration and motor adaption were not affected. This supports the notion that multisensory integration and recalibration are guided by common-cause evidence but deal with sensory discrepancies on different time scales: while integration is prompted by local common-cause evidence and reduces immediate discrepancies instantaneously, recalibration and motor adaptation are prompted by global common-cause evidence and reduce persistent discrepancies.

neuroscience↗

Variance (un)explained: Experimental conditions and temporal dependencies explain similarly small proportions of reaction time variability in perceptual and cognitive tasks

Any series of sensorimotor actions shows fluctuations in speed and accuracy from repetition to repetition, even when the sensory input and motor output requirements remain identical over time. Such fluctuations are particularly prominent in reaction time (RT) series from laboratory neurocognitive tasks. Despite their omnipresent nature, trial-to-trial fluctuations remain poorly understood. Here, we systematically analysed RT series from various neurocognitive tasks, quantifying how much of the total trial-to-trial RT variance can be explained with general linear models (GLMs) by three sources of variability that are frequently investigated in behavioural and neuroscientific research: 1) experimental conditions, employed to induce systematic patterns in variability, 2) short-term temporal dependencies as the autocorrelation between subsequent trials, and 3) long-term temporal trends over experimental blocks and sessions. Furthermore, we examined to what extent the explained variances by these sources are shared or unique. We analysed 1913 unique RT series from 30 different cognitive control and perception-based tasks. On average, the three sources together explained [~]8-17% of the total variance. The experimental conditions explained on average [~]2.5-3.5% but did not share explained variance with temporal dependencies. Thus, the largest part of the trial-to-trial fluctuations in RT remained unexplained by these three sources. Unexplained fluctuations may take on non-linear forms that are not picked up by GLMs. They may also be partially attributable to observable endogenous factors such as fluctuations in brain activity and bodily states. Still, some extent of randomness may be a feature of the neurobiological system rather than just nuisance. Public significance statementWhen we perform stereotyped repetitive sensorimotor actions, these nevertheless exhibit remarkable variability over time even under laboratory conditions. We show that most of this variability is not explained by linear models including two factors frequently studied in experimental psychology or cognitive neuroscience: the manipulations introduced by the experimenters and endogenous temporal dependencies that arise over multiple timescales. This implies that moment-to-moment fluctuations in typical behavioural data are largely unpredictable by linear models. Endogenous processes may also influence these fluctuations even in highly stable environments. It remains an empirical question to what extent exogenous and endogenous sources influence fluctuations non-linearly.

neuroscience↗

Steady state visual evoked potentials reveal a signature of the pitch-size crossmodal association in visual cortex

Crossmodal correspondences describe our tendency to associate sensory features from different modalities with each other, such as the pitch of a sound with the size of a visual object. While such crossmodal correspondences (or associations) are described in many behavioural studies their neurophysiological correlates remain unclear. Under the current working model of multisensory perception both a low- and a high-level account seem plausible. That is, the neurophysiological processes shaping these associations could commence in low-level sensory regions, or may predominantly emerge in high-level association regions of semantic and object identification networks. We exploited steady-state visual evoked potentials (SSVEP) to directly probe this question, focusing on the associations between pitch and the visual features of size, hue or chromatic saturation. We found that SSVEPs over occipital regions are sensitive to the congruency between pitch and size, and a source analysis pointed to an origin around primary visual cortices. We speculate that this signature of the pitch-size association in low-level visual cortices reflects the successful pairing of congruent visual and acoustic object properties and may contribute to establishing causal relations between multisensory objects.

neuroscience↗