Biology subjects

Bremmer, F.

Publications and source records attributed to Bremmer, F..

12 recordsLinked to original sources

bioRxiv2026

The representation of voluntary and reflexive fast eye movements in the macaque lateral intraparietal area (LIP)

The macaque lateral intraparietal area (LIP) is known for its role in visually guided saccades as well as in higher cognitive functions. However, its contribution to more basic visuomotor processes remains unclear. Here, we investigated whether neural activity in area LIP is also related to involuntary reflexive eye movements, specifically the fast phases of optokinetic nystagmus (OKN). To address this question, we compared spiking activity and local field potentials (LFPs) in area LIP of two male macaque monkeys during visually guided saccades and during kinematically similar OKN fast phases. Neurons exhibiting robust perisaccadic activation during voluntary saccades showed markedly reduced or no activity around the time of OKN fast phases and were not modulated by fast-phase amplitude or frequency. Using a Generalized Linear Model, we found that during OKN slow phases, area LIP reliably encoded gaze position and the direction of visual motion driving the reflexive eye movement. LFP analyses further revealed that beta-band power differed between voluntary saccades and OKN fast phases, whereas theta-band phase coherence increased following both types of fast eye movements, suggesting distinct local processing but shared post-movement network coordination. Our results reinforce the view of area LIP as a key area for integrating sensory and cognitive signals relevant for goal-directed action rather than a generic oculomotor controller.

neuroscience↗

bioRxiv2025

Registration-based 3D Light Sheet Fluorescence Microscopy and 2D histology image fusion tool for pathological specimen

BackgroundHistological analysis traditionally relies on thin tissue sections, providing inherently two-dimensional (2D) information. However, this approach captures only a fraction of the entire sample and lacks the spatial context nec-essary for comprehensive tissue assessment. Recent advancements in multimodal imaging have introduced the fusion of histological data with three-dimensional (3D) imaging techniques, such as Light Sheet Fluorescence Microscopy (LSFM), to enhance tissue analysis by integrating complementary spatial information. A key challenge in this fusion process is the accurate alignment of corresponding structures across modalities, which is complicated by differences in resolution, sectioning-induced deformations, and varying imaging orientations. Existing solu-tions often require manual selection of image pairs or technical expertise, limiting accessibility to non-specialist users. MethodsTo address these limitations, we introduce LitSHi (Light Sheet meets Histology), a novel registration tool that enables the automated and precise align-ment of LSFM and histological images. LitSHi allows multimodal image fusion to be performed fully automatically, which significantly reduces the need for manual intervention. ResultsWe evaluated LitSHi on testicular tumor specimens, demonstrating its ability to achieve enhanced structural correspondence between LSFM and histological images. The automated registration process significantly improved efficiency and alignment accuracy compared to traditional manual or semi-automated approaches. ConclusionLitSHi could improve digital pathology by optimizing multimodal tissue analysis and supporting future developments in computational pathology and AI-driven diagnostics.

bioengineering↗

bioRxiv2024

Coding of egocentric distance in the macaque ventral intraparietal area

The encoding of three-dimensional visual spatial information is of ultimate importance in everyday life, in particular for successful navigation toward targets or threat avoidance. Eye-movements challenge this spatial encoding: 2-3 times per second, they shift the image of the outside world across the retina. The macaque ventral intraparietal area (VIP) stands out from other areas of the dorsal where pathway of the primate visual cortical system: many neurons encode visual information irrespective of horizontal and vertical eye position. But does this gaze invariance of spatial encoding at the single neuron level also apply to egocentric distance? Here, concurrent with recordings from area VIP, monkeys fixated a central target at one of three distances (vergence), while a visual stimulus was shown at one of seven distances (disparity). Most neurons activity was modulated independently by both disparity and eye vergence, demonstrating a different type of invariance than for visual directions. By using population activity, we were able to decode egocentric distance of a stimulus which demonstrates that egocentric distances are nonetheless represented within the neuronal population. Our results provide further strong evidence for a role of area VIP in 3D space encoding.

neuroscience↗

bioRxiv2023

Quantitative comparison of a mobile, tablet-based and two stationary, video-based eye-trackers

AbstractThe analysis of eye-movements is a non-invasive, reliable and fast method to detect and quantify brain (dys-)functions. Here, we investigated the performance of two novel eye-trackers: the Thomas-Oculus-Motus-research mobile (TOM-rm) and the TOM-research stationary (TOM-rs) and compared it with the performance of a well-established video-based eye-tracker, i.e., the EyeLink 1000 (EL). The TOM-rm is a fully integrated, tablet-based mobile device that presents visual stimuli and records head-unrestrained eye-movements at 30Hz without additional infrared (IR) illumination. The TOM-rs is a stationary, video-based eye-tracker that records eye-movements at either high spatial or high temporal resolution. We compared the performance of all three eye-trackers in two different behavioral tasks: pro- and anti-saccade and free viewing. We collected data from human subjects while running all three eye-tracking devices in parallel. Parameters requiring a high spatial or temporal resolution (e.g., saccade latency or gain), as derived from the data, differed significantly between the EL and the TOM-rm in the pro- and anti-saccade task. In the free viewing task, larger noise and the lower frame rate of the TOM-rm caused deviations of the results with respect to the EL. Differences between results derived from the TOM-rs and the EL were most likely due to experimental conditions, which could not be optimized for both systems simultaneously. We conclude that the TOM-rm can be used for measuring eye-movements reliably at comparably low spatial and temporal resolution. The TOM-rs, on the other hand, can provide high-resolution oculomotor data at least on a par with an established reference system.

neuroscience↗

bioRxiv2022

High-and Low-Frequency Deep Brain Stimulation in the Subthalamic Nucleus differentially modulate Response Inhibition and Action Selection in Parkinson's Disease

BackgroundWhile deep brain stimulation (DBS) in the subthalamic nucleus (STN) improves motor functions in Parkinsons disease (PD), it has also been associated with increased impulsivity. MethodsA combined approach of eye-tracking and high-density EEG was used to investigate how high- and low-frequency DBS impact impulsive actions in the antisaccade task in a cohort of ten persons with PD. Computational modelling of the behavioral outcomes allowed a nuanced insight into the effect of DBS on response inhibition and action selection processes. Results: Against our expectations, both 130 Hz- and 60 Hz-DBS improved response inhibition as both resulted in a reduced rate of early reflexive errors. Correspondingly, DBS with both frequencies led to increased desynchronization of beta power during the preparatory period which may be a correlate of anticipatory activation in the oculomotor network. Low-frequency DBS additionally was associated with increased midfrontal theta power, an established marker of cognitive control. While higher midfrontal theta power predicted longer antisaccade latencies in off-DBS state on a trial-by-trial basis, 130 Hz-DBS reversed this relationship. As informed by the computational model, 130 Hz-DBS further led to a shift in the speed-accuracy trade-off causing an acceleration and error-proneness of actions later in the trial. ConclusionsOur results disentangle the impact of DBS on early and late impulsive actions. Only 130 Hz-DBS may disrupt theta-mediated cognitive control mechanisms via medial frontal - STN pathways that are involved in delaying action selection. 60 Hz-DBS may provide beneficial effects on response inhibition without the detrimental effect on action selection seen with 130 Hz-DBS. FundingThis study was supported by the SUCCESS program of Philipps-University Marburg (JW), the Hessian Ministry of Sciences and the Arts, clusterproject: The Adaptive Mind - TAM (FB / AK) and the German Research Foundation (DFG). International Research Training Group 1901 (FB / AK)

neuroscience↗

bioRxiv2022

Neural responses to broadband visual flicker in marmoset primary visual cortex

Temporal information is ubiquitous in natural vision and must be represented accurately in the brain to allow us to interact with a constantly changing world. Recent studies have employed a random stimulation paradigm to map the temporal response function (TRF) to luminance changes in the human EEG. This approach has revealed that the visual system, when presented with broadband visual input, actively selects distinct temporal frequencies, and retains their phase-information for prolonged periods of time. This non-linear response likely originates in primary visual cortex (V1), yet, so far it has not been investigated on a neural level. Here, we characterize the steady-state response to random broadband visual flicker in marmoset V1. In two experiments, we recorded from i) marmosets passively stimulated under general anesthesia, and ii) awake marmosets, under free viewing conditions. Our results show that LFP coupling to the stimulus was broadband and unselective under anesthesia, whereas in awake animals, it was restricted to two distinct frequency components, in the alpha and beta range. Within these frequency bands, coupling adhered to the receptive field (RF) boundaries of the local populations. The responses outside the RF did not provide evidence for a propagation of stimulus information across the cortex, contrary to results in human EEG studies. This result may be explained by short fixation durations, warranting further investigation. In summary, our findings show that during awake behavior V1 neural responses to broadband information are selective for distinct frequency bands, and that this selectivity is likely controlled actively by top-down mechanisms.

neuroscience↗

bioRxiv2021

Visual perturbation of balance suggests impaired neuromuscular stability but intact visuo-motor control in Parkinson's disease

Postural instability marks one of the most disabling features of Parkinsons disease (PD), but only reveals itself after affected brain areas have already been significantly damaged. Thus, there is a need to detect deviations in balance and postural control before visible symptoms occur. In this study, we visually perturbed balance in the anterior-posterior direction using sinusoidal oscillations of a moving room in virtual reality at different frequencies. We tested three groups: individuals with PD under dopaminergic medication, an age-matched control group, and a group of young healthy adults. We tracked their centre of pressure and their full-body motion. We investigated sway amplitudes and applied newly introduced phase-locking analyses to investigate responses across participants bodies. Patients exhibited significantly higher sway amplitudes as compared to the control subjects. However, their sway was phase-locked to the visual motion like that of age-matched and young healthy adults. Furthermore, all groups successfully compensated for the visual perturbation by - most likely reflexively - phase-locking their sway to the stimulus. As frequency of the perturbation increased, distribution of phase-locking (PL) across the body revealed a shift of the highest PL-values from the upper body towards the hip-region for young healthy adults, which could not be observed in patients and elderly healthy adults. Our findings suggest an impaired neuromuscular stability, but intact visuomotor processing in early stages of PD, while less flexibility to adapt postural strategy to different perturbations revealed to be an effect of age rather than disease. New & NoteworthyA better understanding of visuomotor control in Parkinsons disease (PD) potentially serves as a tool for earlier diagnosis, which is crucial for improving patients quality of life. In our study, we assess body sway responses to visual perturbations of the balance control system in patients with early-to-mid stage PD, using motion tracking along with recently established phase-locking techniques. Our findings suggest patients at this stage to have an impaired muscular stability but intact visuomotor control.

neuroscience↗

bioRxiv2021

Coding of interceptive saccades in parietal cortex of macaque monkeys

The oculomotor system can initiate remarkably accurate saccades towards moving targets (interceptive saccades) the processing of which is still under debate. The generation of these saccades requires the oculomotor centers to have information about the motion parameters of the target that then must be extrapolated to bridge the inherent processing delays. We investigated to what degree the information about motion of a saccade target is available in the lateral intra-parietal area (area LIP) of macaque monkeys for generation of accurate interceptive saccades. When a multi-layer neural network was trained based on neural discharges from area LIP around the time of saccades towards stationary targets it was also able to predict the end points of saccades directed towards moving targets. This prediction, however, lagged behind the actual post-saccadic position of the moving target by ~80 ms when the whole neuronal sample of 105 neurons was used. We further found that single neurons differentially code for the motion of the target. Selecting neurons with the strongest representation of target motion reduced this lag to ~30 ms which represents the position of the moving target approximately at the onset of the interceptive saccade. We conclude that - similarly to recent findings from the Superior Colliculus (Goffart et al., 2017) - there is a continuum of contributions of individual LIP neurons to the accuracy of interceptive saccades. A contribution of other gaze control centers (like the cerebellum or the frontal eye field) that further increase the saccadic accuracy is, however, likely.

neuroscience↗

bioRxiv2021

Gaze-Related Activity in Primate Frontal Cortex Predicts and Mitigates Spatial Uncertainty

A remarkable feature of primate behavior is the ability to predict future events based on past experience and current sensory cues. To understand how the brain plans movements in the presence of unstable cues, we recorded gaze-related activity in the frontal cortex of two monkeys engaged in a quasi-predictable cue-conflict task. Animals were trained to look toward remembered visual targets in the presence of a landmark that shifted with fixed amplitude but randomized direction. As simulated by a probabilistic model based on known physiology/behavior, gaze end points assumed a circular distribution around the target, mirroring the possible directions of the landmark shift. This predictive strategy was reflected in frontal cortex activity (especially supplementary eye fields), which anticipated future gaze distributions before the actual landmark shift. In general, these results implicate prefrontal cortex in the predictive integration of environmental cues and their learned statistical properties to mitigate spatial uncertainty.

neuroscience↗

bioRxiv2020

Landmark-Centered Coding in Frontal Cortex Visual Responses

Visual landmarks influence spatial cognition [1-3], navigation [4,5] and goal-directed behavior [6-8], but their influence on visual coding in sensorimotor systems is poorly understood [6,9-11]. We hypothesized that visual responses in frontal cortex control gaze areas encode potential targets in an intermediate gaze-centered / landmark-centered reference frame that might depend on specific target-landmark configurations rather than a global mechanism. We tested this hypothesis by recording neural activity in the frontal eye fields (FEF) and supplementary eye fields (SEF) while head-unrestrained macaques engaged in a memory-delay gaze task. Visual response fields (the area of visual space where targets modulate activity) were tested for each neuron in the presence of a background landmark placed at one of four oblique configurations relative to the target stimulus. 102 of 312 FEF and 43 of 256 SEF neurons showed spatially tuned response fields in this task. We then fit these data against a mathematical continuum between a gaze-centered model and a landmark-centered model. When we pooled data across the entire dataset for each neuron, our response field fits did not deviate significantly from the gaze-centered model. However, when we fit response fields separately for each target-landmark configuration, the best fits shifted (mean 37% / 40%) toward landmark-centered coding in FEF / SEF respectively. This confirmed an intermediate gaze / landmark-centered mechanism dependent on local (configuration-dependent) interactions. Overall, these data show that external landmarks influence prefrontal visual responses, likely helping to stabilize gaze goals in the presence of variable eye and head orientations. HighlightsO_LIPrefrontal visual responses recorded in the presence of visual landmarks C_LIO_LIResponse fields showed intermediate gaze / landmark-centered organization C_LIO_LIThis influence depended on specific target-landmark configurations C_LI

neuroscience↗

bioRxiv2018

MicroRNA-449 sustains cilia-related networks in the absence of transcription factor TAp73

Motile cilia serve vital functions in development, homeostasis and regeneration. We recently demonstrated that TAp73 is an essential transcriptional regulator of respiratory motile multiciliogenesis. Here, we show that TAp73 is expressed in multiciliated cells (MCCs) of diverse tissues. Analysis of TAp73-/- animals revealed that TAp73 regulates Foxj1, Rfx2, Rfx3, axonemal dyneins Dnali1 and Dnai1, plays a pivotal role in the generation of MCCs in reproductive ducts, and contributes to fertility. However, in the brain the function of MCCs appears to be preserved upon loss of TAp73, and robust activity from cilia-related networks is maintained in TAp73-/-. Consistent with TAp73-/-, its target miR34bc was reduced, whereas strong and specific induction of miR449 was observed along with an increase in E2f4, that induced transcriptional response from miR449 genomic regions. Depletion of both TAp73 and miR449 resulted in defective multiciliogenesis in the brain and hydrocephalus, indicating that miR449 and potentially additional pro-ciliogenic factors cooperate with TAp73 to ensure brain multiciliogenesis and CP development.

cell biology↗

bioRxiv2017

Predictive orientation remapping maintains a stable retinal percept

Despite motion on the retina with every saccade, we perceive the world as stable. But whether this stability is a result of neurons constructing a spatial map or continually remapping a retinal representation is unclear. Previous work has focused on the perceptual consequences of shifts in the horizontal and vertical dimensions, but torsion is another key component in ocular orienting that - unlike horizontal and vertical movements - produces a natural misalignment between spatial and retinal coordinates. Here we took advantage of oblique eye orientation-induced retinal torsion to examine perisaccadic orientation perception. We found that orientation perception was largely predicted by the retinal image throughout each trial. Surprisingly however, we observed a significant presaccadic remapping of the percept consistent with maintaining a stable (but spatially inaccurate) retinotopic perception throughout the saccade. These findings strongly suggest that our seamless perceptual stability relies on retinotopic signals that are remapped with each saccade.

neuroscience↗