Biology subjects

Giese, M. A.

Publications and source records attributed to Giese, M. A..

14 recordsLinked to original sources

bioRxiv2026

Behavioral characterization of dynamic facial expression perception in rhesus monkeys (Macaca mulatta) using naturalistic and synthetic stimuli

Facial displays are an important channel of communication for primates, yet it remains unclear based on which criteria monkeys evaluate facial expressions. We trained two rhesus macaques to categorize videos of four facial expression types (neutral, lip-smacking, silent bared-teeth (SBT) and open-mouth threat displays) and then tested generalization to novel individuals and avatars while measuring pupillary responses. The animals were able to categorize facial expressions and generalize their classifications to novel, untrained videos, although performance was not perfect. Misclassifications were not driven solely by visual similarity between expression categories, as demonstrated by a novel automated approach integrating deep learning-based motion tracking with the Macaque Facial Action Coding System to enable objective quantification of facial action units. Instead, open-mouth threats were readily categorized correctly and distinguished from lip-smacking, while also eliciting the strongest arousal responses. By contrast, categorization of SBT displays varied substantially across stimulus identities, influenced by body weight, gaze direction, and coordinated movements of eyebrows and ears. Morphed avatar expressions were categorized according to expression component intensity, demonstrating graded perception. Avatar manipulations revealed that categorization was robust against lack of coherent motion, lack of realism beyond a basic level of texture, and to some extent transcended species form boundaries to a human face. However, human facial expressions elicited no systematic categorizations or differential arousal. Our findings indicate that conspecific facial expressions were perceived as functionally meaningful, context-dependent social signals shaped by all components of facial behavior and signaler characteristics, rather than fixed, mouth movement-defined categories.

animal behavior and cognition↗

bioRxiv2025

Rhesus monkeys use both eye and head gaze to reallocate covert spatial attention facilitating visual perception

Non-verbal cues, particularly eye gaze, significantly shape human social interactions. Although non-human primates reliably follow head gaze, their capacity to use eye gaze alone for inferring the others focus of attention remains debated. We investigated this question using a realistic rhesus monkey head avatar that directed its gaze toward one of two LEDs (left or right), employing either eye movements alone or combined eye and head movements. After a randomly chosen interval (ranging 50-400 ms) from gaze presentation, one LED transiently increased its luminance to near-threshold levels. Rhesus monkeys were trained to detect and report this luminance change via a saccade to the corresponding LED, independent of the avatars gaze direction, to receive rewards. Our results showed that head-gaze cues robustly directed covert attention toward gaze-congruent targets with short delays, indicative of reflex-like, stimulus-driven orienting. In contrast, eye gaze alone, at comparable amplitudes, did not affect attention shifts. However, increasing the avatars size and eye-gaze amplitude, simulating a close-range interaction, made eye gaze cues effective in guiding attention. These findings demonstrate that rhesus monkeys possess the capacity to use eye-gaze cues to determine conspecifics attentional targets, and validate and underscore the utility of 3D animal models as powerful tools for generating realistic yet precisely controlled stimuli. Our study supports the idea that eye-gaze following is not uniquely human but is an evolutionarily ancient ability, likely shared across Old World monkeys and apes which diverged more than 30 million years ago.

animal behavior and cognition↗

bioRxiv2025

Neural encoding of biomechanically (im)possible human movements in occipitotemporal cortex

Understanding how the human brain processes body movements is essential for clarifying the mechanisms underlying social cognition and interaction. This study investigates the encoding of biomechanically possible and impossible body movements in occipitotemporal cortex using ultra-high field 7Tesla fMRI. By predicting the response of single voxels to impossible/possible movements using a computational modelling approach, our findings demonstrate that a combination of postural, biomechanical, and categorical features significantly predicts neural responses in the ventral visual cortex, particularly within the extrastriate body area (EBA), underscoring the brains sensitivity to biomechanical plausibility. Lastly, these findings highlight the functional heterogeneity of EBA, with specific regions (middle/superior occipital gyri) focusing on detailed biomechanical features and anterior regions (lateral occipital sulcus and inferior temporal gyrus) integrating more abstract, categorical information.

neuroscience↗

bioRxiv2024

GATA1-deficient human pluripotent stem cells generate neutrophils with improved antifungal immunity that is mediated by the integrin CD18

Neutrophils are critical for host defense against fungi. However, the short life span and lack of genetic tractability of primary human neutrophils has limited in vitro analysis of neutrophil-fungal interactions. Human induced pluripotent stem cell (iPSC)-derived neutrophils (iNeutrophils) are a genetically tractable alternative to primary human neutrophils. Here, we show that deletion of the transcription factor GATA1 from human iPSCs results in iNeutrophils with improved antifungal activity against Aspergillus fumigatus. GATA1 knockout (KO) iNeutrophils have increased maturation, antifungal pattern recognition receptor expression and more readily execute neutrophil effector functions compared to wild-type iNeutrophils. iNeutrophils also show a shift in their metabolism following stimulation with fungal {beta}-glucan, including an upregulation of the pentose phosphate pathway (PPP), similar to primary human neutrophils in vitro. Furthermore, we show that deletion of the integrin CD18 attenuates the ability of GATA1-KO iNeutrophils to kill A. fumigatus but is not necessary for the upregulation of PPP. Collectively, these findings support iNeutrophils as a robust system to study human neutrophil antifungal immunity and has identified specific roles for CD18 in the defense response. Author SummaryNeutrophils are important first responders to fungal infections, and understanding their antifungal functions is essential to better elucidating disease dynamics. Primary human neutrophils are short lived and do not permit genetic manipulation, limiting their use to study neutrophil-fungal interactions in vitro. Human induced pluripotent stem cell (iPSC)-derived neutrophils (iNeutrophils) are a genetically tractable alternative to primary human neutrophils for in vitro analyses. In this report we show that GATA1-deficient iPSCs generate neutrophils (iNeutrophils) that are more mature than wild-type iNeutrophils and display increased antifungal activity against the human fungal pathogen Aspergillus fumigatus. We also show that GATA1-deficient iNeutrophils have increased expression of antifungal receptors than wild-type cells and shift their metabolism and execute neutrophil antifungal functions at levels comparable to primary human neutrophils. Deletion of the integrin CD18 blocks the ability of GATA1-deficient iNeutrophils to kill and control the growth of A. fumigatus, demonstrating an important role for this integrin in iNeutrophil antifungal activity. Collectively, these findings support the use of iNeutrophils as a model to study neutrophil antifungal immunity.

microbiology↗

bioRxiv2024

Real time imaging reveals a role for macrophage protrusive motility in melanoma invasion

Macrophages are primary cells of the innate immune system that mediate tumor progression. However, the motile behavior of macrophages and interactions with tumor cells are not well understood. Here, we exploit the optical transparency of larval zebrafish and perform real time imaging of macrophage-melanoma interactions. We found that macrophages are highly motile in the tumor microenvironment. Macrophages extend dynamic projections between tumor cells that precedes invasive melanoma migration. Modulating macrophage motility with a dominant inhibitory mutation in Rac2 inhibits recruitment to the tumor and impairs tumor invasion. However, a hyperactivating mutation in Rac2 does not affect macrophage recruitment but limits macrophage projections into the melanoma mass and reduces invasive melanoma cell migration. Taken together, these findings reveal a role for Rac2-mediated macrophage protrusive motility in melanoma invasion.

cell biology↗

bioRxiv2024

Single cell autofluorescence imaging reveals immediate metabolic shifts of neutrophils with activation across biological systems

Neutrophils, the most abundant leukocytes in human peripheral circulation, are crucial for the innate immune response. They are typically quiescent but rapidly activate in response to infection and inflammation, performing diverse functions such as oxidative burst, phagocytosis, and NETosis, which require significant metabolic adaptation. Deeper insights into such metabolic changes will help identify regulation of neutrophil functions in health and diseases. Due to their short lifespan and associated technical challenges, the metabolic processes of neutrophils are not completely understood. This study uses optical metabolic imaging (OMI), which entails optical redox ratio and fluorescence lifetime imaging microscopy of intrinsic metabolic coenzymes NAD(P)H and FAD to assess the metabolic state of single neutrophils. Primary human neutrophils were imaged in vitro under a variety of activation conditions and metabolic pathway inhibitors, while metabolic and functional changes were confirmed with mass spectrometry, oxidative burst, and NETosis measurements. Our findings show that neutrophils undergo rapid metabolic remodeling to a reduced redox state indicated by changes in NAD(P)H lifetime and optical redox ratio, with a shift to an oxidized redox state during activation. Additionally, single cell OMI analysis reveals a heterogeneous metabolic response across neutrophils and human donors to live pathogen infection (Pseudomonas aeruginosa and Toxoplasma gondii). Finally, consistent OMI changes with activation were confirmed between in vitro human and in vivo zebrafish larvae neutrophils. This study demonstrates the potential of OMI as a versatile tool for studying neutrophil metabolism and underscores its use across different biological systems, offering insights into neutrophil metabolic activity and function at a single cell level.

immunology↗

bioRxiv2024

MacAction: Realistic 3D macaque body animation based on multi-camera markerless motion capture

Social interaction is crucial for survival in primates. For the study of social vision in monkeys, highly controllable macaque face avatars have recently been developed, while body avatars with realistic motion do not yet exist. Addressing this gap, we developed a pipeline for three-dimensional motion tracking based on synchronized multi-view video recordings, achieving sufficient accuracy for life-like full-body animation. By exploiting data-driven pose estimation models, we track the complete time course of individual actions using a minimal set of hand-labeled keyframes. Our approach tracks single actions more accurately than existing pose estimation pipelines for behavioral tracking of non-human primates, requiring less data and fewer cameras. This efficiency is also confirmed for a state-of-the-art human benchmark dataset. A behavioral experiment with real macaque monkeys demonstrates that animals perceive the generated animations as similar to genuine videos, and establishes an uncanny valley effect for bodies in monkeys.

animal behavior and cognition↗

bioRxiv2023

Human Arm Redundancy - A New Approach for the Inverse Kinematics Problem

The inverse kinematics problem deals with the question of how the nervous system coordinates movement to resolve redundancy, such as in the case of arm reaching movements where more degrees of freedom are available at the joint versus hand level. In particular, this work focuses on determining which coordinate frames can best represent human movements, allowing the motor system to solve the inverse kinematics problem in the presence of kinematic redundancies. In particular, in this work we used a multi-dimensional sparse source separation method called FADA to derive sets of basis functions (here called sources) for both the task and joint spaces, with joint space being represented in terms of either the absolute or anatomical joint angles. We assessed the similarities between the joint and task sources in each of these joint representations. We found that the time-dependent profiles of the absolute reference frames sources show greater similarity to those of the corresponding sources in the task space. This result was found to be statistically significant. Hence, our analysis suggests that the nervous system represents multi-joint arm movements using a limited number of basis functions, to allow for simple transformations between task and joint spaces. Importantly, joint space seems to be represented in terms of an absolute reference frame to achieve successful performance and simplify inverse kinematics transformations in the face of the existing kinematic redundancies. Further studies will be needed to determine the generalizability of this finding and its implications for neural control of movement.

neuroscience↗

bioRxiv2021

Turning movements in real life capture subtle longitudinal and preataxic changes in cerebellar ataxia

OBJECTIVESClinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints which capture change in ataxia severity in patients real life. This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real life turning movements which are sensitive for changes both longitudinally and at the preataxic stage. METHODSCombined cross-sectional (n=30) and longitudinal (n=14, 1-year interval) observational study in degenerative cerebellar disease (including 8 pre-ataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body-worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real-life movements. RESULTSMeasures which quantified dynamic balance during turning - lateral velocity change (LVC) and outward acceleration -, but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life with high effect size ({delta}=0.68), with LVC also differentiating preataxic against healthy subjects ({delta}=0.53). LVC was highly correlated with clinical ataxia severity (SARA score, effect size {rho}=0.79) and subjective balance confidence (ABC score, {rho}=0.66). Moreover, LVC in real life - but not general turning measures, gait measures, or the SARA score - allowed detecting significant longitudinal change in one-year follow-up with high effect size (rprb=0.66). CONCLUSIONSMeasures of turning allow to capture specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers for capturing change in real life, even in the highly treatment-relevant early stages of degenerative cerebellar disease.

bioengineering↗

bioRxiv2019

Towards ecologically valid biomarkers: real-life gait assessment in cerebellar ataxia

BACKGROUNDWith disease-modifying drugs on the horizon for degenerative ataxias, motor biomarkers are highly warranted. While ataxic gait and its treatment-induced improvements can be captured in laboratory-based assessments, quantitative markers of ataxic gait in real life will help to determine ecologically meaningful improvements.\n\nOBJECTIVESTo unravel and validate markers of ataxic gait in real life by using wearable sensors.\n\nMETHODSWe assessed gait characteristics of 43 patients with degenerative cerebellar disease (SARA:9.4{+/-}3.9) compared to 35 controls by 3 body-worn inertial sensors in three conditions: (1) laboratory-based walking; (2) supervised free walking; (3) real-life walking during everyday living (subgroup n=21). Movement analysis focussed on measures of movement smoothness and spatio-temporal step variability.\n\nRESULTSA set of gait variability measures was identified which allowed to consistently identify ataxic gait changes in all three conditions. Lateral step deviation and a compound measure of step length categorized patients against controls in real life with a discrimination accuracy of 0.86. Both were highly correlated with clinical ataxia severity (effect size {rho}=0.76). These measures allowed detecting group differences even for patients who differed only 1 point in the SARAp&g subscore, with highest effect sizes for real-life walking (d=0.67).\n\nCONCLUSIONSWe identified measures of ataxic gait that allowed not only to capture the gait variability inherent in ataxic gait in real life, but also demonstrate high sensitivity to small differences in disease severity - with highest effect sizes in real-life walking. They thus represent promising candidates for quantitative motor markers for natural history and treatment trials in ecologically valid contexts.

bioengineering↗

bioRxiv2019

Cerebellar involvement in learning to balance a cart-pole system

The role of the cerebellum in error-based motor adaptation is well examined. In contrast, the involvement of the cerebellum in reward-based motor learning is less clear. In this study, we examined cerebellar involvement in a reward-based motor learning task, namely learning to control a virtual cart-pole system, over five consecutive days. Subjects with focal cerebellar lesions were compared to age-matched controls in terms of learning performance and underlying control mechanisms.\n\nBased on the overall balancing performance we have identified two subgroups of patients: (1) patients with learning performance comparable to healthy controls and (2) patients with decelerated learning, unsaturated learning progress after five days and decreased inter-manual transfer. Furthermore, we found that online learning is impaired while offline learning is partly preserved in cerebellar subjects. Regarding control mechanisms, decreased control performance was associated with impairments in predictive action timing.\n\nVoxel-wise lesion symptom mapping based on the two subgroups revealed strong associations between impairments in controlling the virtual cart-pole system and lesions in intermediate and lateral parts of lobules V and VI. These results together with previous reports suggest that the ability to predict the dynamics of the cart-pole system is an important factor for the reward-based skill acquisition process.

neuroscience↗

bioRxiv2017

Motor expertise facilitates the precision of state extrapolation in perception

Predicting the behavior of objects in the environment is an important requirement to overcome latencies in the sensorimotor system and realize precise actions in rapid situations. Internal forward models that were acquired during motor training might not only be used for efficiently controlling fast motor behavior but also to facilitate extrapolation performance in purely perceptual tasks. In this study, we investigated whether preceding virtual cart-pole balancing training facilitates the ability to extrapolate the pole motion. We compared a group of 10 subjects, proficient in performing the cart-pole balancing task, to 10 naive subjects. Our results demonstrate that preceding motor training increases the precision of pole movement extrapolation, although extrapolation is not trained explicitly. Additionally, we modelled subjects behaviors and show that the difference in extrapolation performance can be explained by individual differences in the accuracy of internal forward models. When subjects are provided with feedback about the true pole movement in a second phase, both groups improve rapidly. The results indicate that the perceptual capability to extrapolate the state of the cart-pole system accurately is implicitly trained during motor learning. We discuss these results in the context of shared representations and action-perception transfer.

neuroscience↗

bioRxiv2017

Interacting Learning Processes During Skill Acquisition: Learning To Control With Gradually Changing System Dynamics

There is increasing evidence that sensorimotor learning under real-life conditions relies on a composition of several learning processes. Nevertheless, most studies examine learning behaviour in relation to one specific learning mechanism. In this study, we examined the interaction between reward-based skill acquisition and motor adaptation to changes of object dynamics. Thirty healthy subjects, split into two groups, acquired the skill of balancing a pole on a cart in virtual reality. In one group, we gradually increased the gravity, making the task easier in the beginning and more difficult towards the end. In the second group, subjects had to acquire the skill on the maximum, most difficult gravity level. We hypothesized that the gradual increase in gravity during skill acquisition supports learning despite the necessary adjustments to changes in cart-pole dynamics. We found that the gradual group benefits from the slow increment, although overall improvement was interrupted by the changes in gravity and resulting system dynamics, which caused short-term degradations in performance and timing of actions. In conclusion, our results deliver evidence for an interaction of reward-based skill acquisition and motor adaptation processes, which indicates the importance of both processes for the development of optimized skill acquisition schedules.

neuroscience↗

bioRxiv2017

Improved Kinect sensor based motion capturing system for gait assessment

Optical motion capturing systems are expensive and require substantial dedicated space to be set up. On the other hand, they provide unsurpassed accuracy and reliability. In many situations however flexibility is required and the motion capturing system can only temporarily be placed. The Microsoft Kinect v2 sensor is comparatively cheap and with respect to gait analysis promising results have been published. We here present a motion capturing system that is easy to set up, flexible with respect to the sensor locations and delivers high accuracy in gait parameters comparable to a gold standard motion capturing system (VICON). Further, we demonstrate that sensor setups which track the person only from one-side are less accurate and should be replaced by two-sided setups. With respect to commonly analyzed gait parameters, especially step width, our system shows higher agreement with the VICON system than previous reports.

neuroscience↗