Biology subjects

Nolte, D.

Publications and source records attributed to Nolte, D..

12 recordsLinked to original sources

bioRxiv2026

Exploring Neural Signatures of Self-Initiated Saccadic and Blink Events in the Real World

During natural vision, the human brain constantly has to account for self-produced interruptions of visual input, through blinks and saccades, to maintain a stable perception of the world. It remains unclear whether these event-related neural responses are treated similarly due to a common underlying mechanism. To systematically investigate this functional connection, we recorded synchronized mobile EEG and eye-tracking data from freely moving participants as they (visually) explored a city center. Our results replicate prior findings showing that a substantial portion of the neural response is aligned to event onsets in comparison to offset, underscoring the relevance of investigating the beginning and end of these events. Using advanced deconvolution techniques, we disentangled overlapping, time-locked neural contributions associated with the onsets and offsets of saccades and blinks. The results demonstrate that the deconvoluted neural kernels are highly correlated when comparing saccade onset to blink onset, as well as saccade offset to blink offset, for both evoked and induced activity across electrodes. Together, our findings demonstrate that despite their distinct physical profiles, saccades and blinks share a common neural signature that governs both their onset and offset dynamics during unconstrained real-world behavior. HighlightsO_LICo-registration of portable EEG and Eye-Tracking yielded meaningful real world data. C_LIO_LIWe studied blinks and saccades as natural interruptions of visual processes. C_LIO_LIAligning EEG data to onset and offset underscored the relevance of both timepoints. C_LIO_LIWe deconvoluted overlapping neural activity for onsets/offsets of saccades/blinks. C_LIO_LIERPs and TFRs are highly correlated for onset/offset of blinks and saccades. C_LI

neuroscience↗

bioRxiv2026

Linking visual and spatial exploration dynamics during free navigation in a large-scale virtual city

Balancing exploration and exploitation is a fundamental challenge for adaptive behavior, yet it remains unclear whether visual sampling and spatial locomotion reflect a single cross-domain trait or operate independently. We addressed this question by recording head-mounted eye-tracking and full-body motion tracking while 26 participants freely navigated "Westbrook", a large-scale virtual city for a total of 150 min across five sessions. From the movement trajectories we derived three spatial descriptors: median walking speed, occupancy entropy, and the proportion of explorative route choices. From the gaze data, we computed 38 robust visual descriptors encompassing fixation dynamics, pupil size, saccadic amplitude, gaze-head alignment, and transition entropy. Principal-component analysis reduced the visual descriptors to three components that captured 58 % of variance, with the first component (PC1) reflecting "gaze dynamism" (frequent shifts, larger saccades, higher transition entropy). Canonical correlation analysis revealed a strong coupling between spatial and visual behaviours: the first pair of canonical variates correlated at r = 0.68 (cross-validated r = 0.45), driven primarily by the association of high walking speed and occupancy entropy with elevated gaze dynamism. In contrast, the proportion of explorative route choices contributed little to this coupling. These findings demonstrate that individual differences in low-level locomotor speed and spatial coverage co-vary with an exploratory visual style, supporting the existence of a domain-general "exploration" factor that shapes both how people move through, and attend to, complex environments.

neuroscience↗

bioRxiv2025

Mobile Eye Tracking in the Real World: Best Practices

As research on human behavior, such as spatial navigation, increasingly adopts naturalistic settings, establishing best practices for such experiments becomes essential. While virtual reality (VR) offers a bridge between laboratory control and real-world complexity, it does not fully capture the experiential richness of real-world environments. Here, we present a demonstration of a mobile eye-tracking study conducted in a large-scale, outdoor urban environment, featuring unconstrained, long-duration free exploration and outside-pointing tasks. Using the city of Limassol, Cyprus as our testbed, we showcase the feasibility of collecting high-quality mobile eye-tracking, head orientation, and GPS data "in the wild," capturing a wide range of natural behavior with minimal experimental constraints. Based on this experience, we provide a set of best practices tailored to the logistical and methodological challenges posed by complex, real-world urban settings, challenges unlikely to arise in traditional indoor or highly controlled environments. While these recommendations have general relevance, we exemplify them in the context of spatial navigation research. By establishing methodological standards for studies at this scale, we aim to encourage and inform future research into naturalistic human behavior outside the laboratory.

neuroscience↗

bioRxiv2025

Beyond the first glance: How human presence enhances visual entropy and promotes spatial learning

Spatial learning emerges not only from static environmental cues but also from the social and semantic context embedded in our surroundings. This study investigates how human agents influence visual exploration and spatial knowledge acquisition in a controlled Virtual Reality (VR) environment, focusing on the role of contextual congruency. Participants freely explored a 1 km2 virtual city while their eye movements were recorded. Agents were visually identical across conditions but placed in locations that were either congruent, incongruent, or neutral with respect to the surrounding environment. Using Bayesian hierarchical modeling, we found that incongruent agents elicited longer fixations and significantly higher gaze transition entropy (GTE), a measure of scanning variability. Crucially, GTE emerged as the strongest predictor of spatial recall accuracy. These findings suggest that human-contextual incongruence promotes more flexible and distributed visual exploration, thereby enhancing spatial learning. By showing that human agents shape not only where we look but how we explore and encode space, this study contributes to a growing understanding of how social meaning guides attention and supports navigation. Author summaryWhen people explore a new environment, such as an unfamiliar city, they rely on what they see to understand and remember the space. Traditionally, research has focused on stable features like buildings or landmarks. However, real-world environments also include people, whose presence can shape how we explore and learn. In this study, participants explored a virtual city while their eye movements were tracked. Some human figures matched their surroundings, while others appeared out of place. We found that people looked longer at those unexpected figures and that their gaze patterns became more flexible and varied afterward. This broader visual exploration helped them remember the layout of the city more accurately. Our results suggest that human presence, especially when it disrupts expectations, can promote more effective learning by encouraging more complex visual engagement. These findings can provide insight into how strategically placed social cues enhance attention and memory, and more importantly, how they influence our patterns of visual exploration.

neuroscience↗

bioRxiv2025

Exploring brain dynamics within the Approach-Avoidance Bias

Approach-avoidance behaviors (AAB) are fundamental mechanisms that guide interactions with the environment based on the emotional valence of stimuli. While previous research has extensively explored behavioral aspects of the AAB, the neural dynamics underlying these processes remain insufficiently understood. The present study employs electroencephalography (EEG) to systematically investigate the neural correlates of AAB in a non-clinical population, focusing on stimulus- and response-locked event-related potentials (ERPs). Forty-three participants performed a classic Approach-Avoidance Task (AAT) while EEG activity was recorded. Behavioral results confirmed the AAB effect, with faster reaction times in congruent compared to incongruent trials, as well for positive versus negative trials. ERP analyses revealed significant differences in the Valence factor, with early effects for stimulus-locked trials and late differences at the parietal-occipital region for response-locked trials. However, no significant effects were found for the Condition factor, suggesting that the neural mechanisms differentiating congruent and incongruent responses might not be optimally captured through EEG. Additionally, frontal alpha asymmetry (FAA) analyses showed no significant differences between conditions, aligning with the literature. These findings provide novel insights into the temporal and spatial characteristics of AAB-related neural activity, emphasizing the role of early visual processing and motor preparation in affect-driven decision-making. Future research should incorporate methodological approaches for assessing AAB in ecologically valid settings.

neuroscience↗

bioRxiv2024

The impact of human agents on spatial navigation and knowledge acquisition in a Virtual Environment

Concepts of spatial navigation rest on the idea of landmarks, which are immobile features or objects in the environment. However, behaviorally relevant objects or fellow humans are often mobile. This raises the question of how the presence of human agents influences spatial exploration and knowledge acquisition. Here, we investigate exploration and performance in subsequent spatial tasks within a virtual environment containing numerous human avatars. In the exploration phase, agents had a locally limited effect on navigation. They prompted participants to revisit locations with agents during their initial exploration without significantly altering overall exploration patterns or the extent of the area covered. However, agents and buildings competed for visual attention. When spatial recall was tested, pointing accuracy toward buildings improved when participants directed their attention to the buildings and nearby agents. In contrast, pointing accuracy for agents showed weaker performance and did not benefit from visual attention directed toward the adjacent building. Active agents and incongruent agent-environment pairings further enhanced pointing accuracy, revealing that violations of expectations by agents can significantly shape navigational knowledge acquisition. Overall, agents influenced spatial exploration by directing attention locally, with the interaction between agent salience and environmental features playing a key role in shaping navigational knowledge acquisition.

neuroscience↗

bioRxiv2024

Investigating saccade-onset locked EEG signatures of face perception during free-viewing in a naturalistic virtual environment

Current research strives to investigate cognitive processes under natural conditions. Virtual reality and EEG are promising techniques combining naturalistic settings with close experimental control. However, many questions and technical challenges remain, e.g., are fixation or saccade onsets a suitable replacement as key events in continuous gaze trajectories (Amme et al., 2024), and can VR effectively capture differences across experimental conditions (Rossion & Jacques, 2008)? To address both questions, we investigate the N170 face effect in a free-viewing immersive VR study that contained houses, various background stimuli, and, notably, static and moving pedestrians to study face perception under naturalistic conditions. Our results show that aligning trials to saccade-onset leads to more well-defined ERPs, especially for the P100 component, and support that saccade-onset ERPs are the better-suited analysis method than fixation-onset ERPs for this type of experiment. Further, we observe an evolution of condition-based differences, i.e., face vs. background fixations, compatible with previous reports but extending in a large temporal window and including all electrode sites at different points in time. In summary, experiments combining VR, EEG, and eye-tracking provide further insights into the processing of faces and the relevance of saccadic onsets as event triggers under natural conditions. Significance StatementWith the effort of investigating and understanding cognitive processes under naturalistic conditions, combining virtual reality and EEG can be fruitful to implement free-viewing studies. The current work combines these technologies to explore key challenges in the context of face perception in an immersive virtual environment. Our results show that saccade-onset ERPs yield more precise measurements when analyzing continuous eye-tracking data than fixation onsets. Furthermore, when processing face compared to background stimuli, distinct temporal patterns encompassing all electrode sites can be observed, offering new insights into face perception. Overall, this work highlights the potential of integrating VR and EEG to advance our understanding of cognitive processes in naturalistic settings.

neuroscience↗

bioRxiv2024

Combining EEG and Eye-Tracking in Virtual Reality - Obtaining Fixation-Onset ERPs and ERSPs

Extensive research conducted in controlled laboratory settings has prompted an inquiry into how results can be generalized to real-world situations influenced by the subjects actions. Virtual reality lends itself ideally to investigating complex situations but requires accurate classification of eye movements, especially when combining it with time-sensitive data such as EEG. We recorded eye-tracking data in virtual reality and classified it into gazes and saccades using a velocity-based classification algorithm, and we cut the continuous data into smaller segments to deal with varying noise levels, as introduced in the REMoDNav algorithm. Furthermore, we corrected for participants translational movement in virtual reality. Various measures, including visual inspection, event durations, and the velocity and dispersion distributions before and after gaze onset, indicate that we can accurately classify the continuous, free-exploration data. Combining the classified eye-tracking with the EEG data, we generated fixation-onset ERPs and ERSPs, providing further evidence for the quality of the eye movement classification and timing of the onset of events. Finally, investigating the correlation between single trials and the average ERP and ERSP identified that fixation-onset ERSPs are less time-sensitive, require fewer repetitions of the same behavior, and are potentially better suited to study EEG signatures in naturalistic settings. We modified, designed, and tested an algorithm that allows the combination of EEG and eye-tracking data recorded in virtual reality.

neuroscience↗

bioRxiv2020

Tissue Dynamics Spectroscopic Imaging: Functional Imaging of Heterogeneous Cancer Tissue

SignificanceTumor heterogeneity poses a challenge for the chemotherapeutic treatment of cancer. Tissue dynamics spectroscopy (TDS) captures dynamic contrast and can capture the response of living tissue to applied therapeutics, but the current analysis averages over the complicated spatial response of living biopsy samples. AimTo develop tissue dynamics spectroscopic imaging (TDSI) to map the heterogeneous spatial response of tumor tissue to anticancer drugs. ApproachTDSI is applied to tumor spheroids grown from cell lines and to ex vivo living esophageal biopsy samples. Doppler fluctuation spectroscopy is performed on a voxel basis to extract spatial maps of biodynamic biomarkers. Functional images and bivariate spatial maps are produced using a bivariate color merge to represent the spatial distribution of pairs of signed drug-response biodynamic biomarkers. ResultsWe have mapped the spatial variability of drug responses within biopsies and have tracked sample-to-sample variability. Sample heterogeneity observed in the biodynamic maps is associated with histological heterogeneity observed using inverted Selective-Plane Illumination Microscopy (iSPIM). ConclusionWe have demonstrated the utility of TDSI as a functional imaging method to measure tumor heterogeneity and its potential for use in drug-response profiling.

biophysics↗

bioRxiv2020

Intracellular Optical Doppler Phenotypes of Chemosensitivity in Human Epithelial Ovarian Cancer

Development of an assay to predict response to chemotherapy has remained an elusive goal in cancer research. We report a phenotypic chemosensitivity assay for epithelial ovarian cancer based on Doppler spectroscopy of infrared light scattered from intracellular motions in living three-dimensional tumor biopsy tissue measured in vitro. The study analyzed biospecimens from 20 human patients with epithelial ovarian cancer. Matched primary and metastatic tumor tissues were collected for 3 patients, and an additional 3 patients provided only metastatic tissues. Doppler fluctuation spectra were obtained using full-field optical coherence tomography through off-axis digital holography. Frequencies in the range from 10 mHz to 10 Hz are sensitive to changes in intracellular dynamics caused by platinum-based chemotherapy. Metastatic tumor tissues were found to display a biodynamic phenotype that was similar to primary tissue from patients who had poor clinical outcomes. The biodynamic phenotypic profile correctly classified 90% [88% to 91% c.i.] of the patients when the metastatic samples were characterized as having a chemoresistant phenotype. This work suggests that Doppler profiling of tissue response to chemotherapy has the potential to predict patient clinical outcomes based on primary, but not metastatic, tumor tissue.

biophysics↗

bioRxiv2020

Integration of Biodynamic Imaging and RNA-seq predicts chemotherapy response in canine diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a common, aggressive cancer of notorious genotypic and phenotypic heterogeneity. A major challenge is predicting response to drug treatment, which has typically been done using genomic tools alone with little success. A novel method that incorporates phenotypic profiling for predicting the effectiveness of therapy for individual patients is desperately needed. BioDynamic Imaging (BDI) is a technique for measuring time-dependent fluctuations in back-scattered light through living tumor tissues to identify critical changes in intracellular dynamics that are associated with phenotypic response to drugs. In this study, BDI and RNA sequencing (RNA-seq) data were collected on tumor samples from dogs with naturally occurring DLBCL, an animal model of increasingly recognized relevance to the human disease. BDI and RNA-seq data were combined to identify correlations between gene co-expression modules and linear combinations of biomarkers to provide biological mechanistic interpretations of BDI biomarkers. Using regularized multivariate logistic regression, we combined RNA-seq and BDI data to develop a novel model to accurately classify the clinical response of canine DLBCL to combination chemotherapy (i.e. CHOP). Our model incorporates data on the expression of 4 genes and 3 BDI-derived phenotypic biomarkers, capturing changes in transcription, microtubule related processes, and apoptosis. This pilot study suggests that the combination of multi-scale transcriptomic and phenotypic data can identify patients that respond to a given treatment a priori in a disease that has been difficult to treat. Our work provides an important framework for future development of strategies and treatments in precision cancer medicine.

cancer biology↗

bioRxiv2019

Learning of Spatial Properties of a Large-scale Virtual City with an Interactive Map

On the basis of embodied/-enacted theories of the mind, investigations of spatial cognition related to real world environments have become current research interests. How this perspective relates to acquiring spatial knowledge not by active exploration, but through map learning, however, remains unresolved. Therefore, we designed a large virtual city comprised of over 200 houses, suitable for active exploration or spatial learning based on a map. Here, we report our results after single and repeated 30-minute training sessions using an interactive city map. We tested subjects knowledge of the orientation of houses towards cardinal north and of two houses relative to each other and the locations of two houses towards each other in a pointing task. Our results revealed that a single training session was sufficient to repeatedly view the majority of houses covering a large area of the city. However, repeated training sessions were necessary to improve the performance level and reveal significant differences between tasks. In contrast to a previous study in a real world city, performance in the two orientation tasks was better than in the pointing task. The lack of distance and the lack of angular difference effects onto task performance suggest the use of a global reference frame. Performance was positively correlated with a self-report on spatial abilities (FRS) in the absolute orientation and pointing task but not the relative orientation task. Overall, our results suggest that training with an interactive city map enhances abstract knowledge, not directly available from an embodied perspective.

neuroscience↗