Biology subjects

Reimann, H.

Publications and source records attributed to Reimann, H..

11 recordsLinked to original sources

bioRxiv2026

A pro-inflammatory effector-memory T cell program links peripheral EBV priming to CNS autoimmunity

T and B cell-mediated immunosurveillance of the central nervous system (CNS) can become maladaptive in multiple sclerosis (MS). Epstein-Barr virus (EBV) is a likely driver of MS, yet how exactly EBV-specific T cells contribute remains unclear. We generated an antigen-resolved atlas of blood and cerebrospinal fluid (CSF) T cells from untreated MS patients and controls. T cell clones carrying a GZMK effector-memory program in blood were CSF-biased, particularly in MS, and associated with EBV reactivity. In CSF, EBV-reactive GZMK CD8 T cells engaged B lineage cells. Activated CD8 T cells promoted atypical B cell and plasmablast formation, whereas GZMK-enriched effector-memory cells induced IL-6 and IL-8 release from myeloid cells. Together, these findings identify an infection-imprinted, CNS-biased state and support a model in which EBV-specific CD8 T cells contribute to inflammation through a non-canonical mode of B cell and myeloid cell activation.

immunology↗

bioRxiv2025

The Relationship Between Visual Motion Detection Thresholds and Visual Sensitivity to Medial/Lateral Balance Control

The ability to differentiate between self-motion and motion in the environment is an important factor for maintaining upright balance control. Visual motion can elicit the sensation of a fall by cueing a false position sense. While there is evidence supporting the role of central vision and fall risk, including measures of contrast sensitivity, depth perception, and size of the visual field, the relationship between motion detection thresholds and balance control remains unknown. The aim of this study is to explore the relationship between thresholds for visual motion detection (VMDTs) of the environment and measures of visual sensitivity to balance disturbances in the environment while walking. Thirty young adults (18-35 years) and thirty older adults (55-79 years) participated in a counter-balanced study where they 1) walked on a self-paced treadmill within a virtual environment that delivered frontal plane multi-sine visual disturbances at three amplitudes (6{degrees}, 10{degrees}, and 15{degrees}), and 2) performed 100 trials of a two-alternative forced choice (2AFC) task in which they discriminated between a counterclockwise ("left") and clockwise ("right") rotation of a visual scene under three conditions (standing, standing with optic flow, and walking). Visual sensitivity was measured using frequency response functions of the center of mass displacement relative to the screen tilt (cm/deg) while VMDTs were measured by fitting a psychometric curve to the responses of the 2AFC task. We found significant positive correlations between measures of visual sensitivity and VMDTs for 7 out of the 9 conditions in young adults, and nonsignificant positive correlations between the two measures in older adults. VMDTs were overall higher in older adults, although not significantly in the standing condition, indicating more motion in the environment is required for older adults to consciously perceive it. VMDTs also tended to increase from standing, standing with optic flow, and walking, although not significantly between the standing and standing with optic flow conditions for both populations. We interpret the positive correlations between the two measures as an indication that individuals with lower motion detection thresholds can more accurately differentiate between self-motion and motion in the environment, resulting in lower responses from visual disturbances in the environment.

neuroscience↗

bioRxiv2024

SENSITIVITY OF MEDIAL/LATERAL BALANCE CONTROL TO VISUAL DISTURBANCES WHILE WALKING IN YOUNG AND OLDER ADULTS

Humans integrate multiple sources of sensory information to estimate body orientation in space. Balance control experiments while standing provide evidence that the contributions of these sensory channels change under different conditions in a process called sensory reweighting. This study aims to address whether there is evidence for sensory reweighting while walking and explores age-related differences in medial/lateral balance control under visually perturbing walking conditions. Thirty young adults (18-35 years) and thirty older adults (55-79 years) walked on a self-paced treadmill within a virtual environment that delivered frontal plane multi-sine visual disturbances at three amplitudes (6{degrees}, 10{degrees}, and 15{degrees}). Frequency response functions were used to quantify visual sensitivity to balance disturbances, while spatiotemporal gait parameters (e.g., step width, step-width variability) were measured to assess balance control. Visual sensitivity decreased in both populations with increasing stimulus amplitude, analogous to the sensory reweighting hypothesis in balance control while standing. Despite the decrease in visual sensitivity, the compensatory upweighting of other sensory systems was not observed through measurements of remnant sway. Older adults exhibited higher visual sensitivity at all amplitudes compared to young adults, indicating a more sensitive response to visual disturbances to balance control. Both groups showed increases in step width and step width variability with higher visual amplitudes, with older adults demonstrating more pronounced effects. Weak correlations existed between changes in visual sensitivity and changes in step width and step width variability suggesting a limited interaction between sensory reweighting and gait stability.

neuroscience↗

bioRxiv2023

Visual Motion Detection Thresholds Can Be Reliably Measured During Walking and Standing

In upright standing and walking, the motion of the body relative to the environment is estimated from a combination of visual, vestibular and somatosensory cues. Associations between vestibular or somatosensory impairments and balance problems are well established, but less is known about how the ability of the visual system to detect motion affects balance control. Here we asked whether motion detection thresholds can be reliably measured during walking and standing. Typically, motion threshold values have been obtained while sitting, with the head fixated to eliminate self-motion. In this study we 1) tested whether a visual motion detection threshold can be reliably measured during standing and walking in the presence of natural self-motion; and 2) investigated whether visual motion detection thresholds differ during standing and walking. MethodsTwenty-nine subjects stood on and walked along a self-paced, instrumented treadmill inside a virtual environment displayed on a large dome. Participants performed a 2-alternative forced choice experiment in which they discriminated between a counterclockwise ("left") and clockwise ("right") rotation of a visual scene projected on a large dome. A 6-down 1-up adaptive staircase algorithm was implemented to change the amplitude of the rotation. A psychometric fit to the participants binary responses provided an estimate for the detection threshold ResultsWe found strong correlations between the repeated measurements in both the walking (R = 0.84, p < 0.001) and the standing condition (R = 0.73, p < 0.001) as well as good agreement between the repeated measures with Bland-Altman plots. Average thresholds during walking (mean = 1.04 degrees, SD = 0.43 degrees) were significantly higher than during standing (mean = 0.73 degrees, SD = 0.47 degrees). ConclusionVisual motion detection thresholds can be reliably measured during both walking and standing, and thresholds are higher during walking.

neuroscience↗

bioRxiv2023

The condition for dynamic stability in humans walking with feedback control

The walking human body is mechanically unstable. Loss of stability and falling is more likely in certain groups of people, such as older adults or people with neuromotor impairments, as well as in certain situations, such as when experiencing conflicting or distracting sensory inputs. Stability during walking is often characterized biomechanically, by measures based on body dynamics and the base of support. Neural control of upright stability, on the other hand, does not factor into commonly used stability measures. Here we analyze stability of human walking accounting for both biomechanics and neural control, using a modeling approach. We define a walking system as a combination of biomechanics, using the well known inverted pendulum model, and neural control, using a proportional-derivative controller for foot placement based on the state of the center of mass at midstance. We analyze this system formally and show that for any choice of system parameters there is always one periodic orbit. We then determine when this periodic orbit is stable, i.e. how the neural control gain values have to be chosen for stable walking. Following the formal analysis, we use this model to make predictions about neural control gains and compare these predictions with the literature and existing experimental data. The model predicts that control gains should increase with decreasing cadence. This finding appears in agreement with literature showing stronger effects of visual or vestibular manipulations at different walking speeds. Author summaryThe walking human body is mechanically unstable and humans frequently lose upright stability and fall while walking. Stability of human walking is usually analyzed from a biomechanical perspective. We argue that sensorimotor control is an essential aspect of walking stability. We model a walking system as a combination of inverted pendulum biomechanics and a neural feedback controller for foot placement and analyze the properties of this hybrid dynamical system. We find that there is always exactly one periodic orbit and derive a criterion for the asymptotic stability of this periodic orbit. This analytic criterion allows us to characterize the region in the parameter space where the walking system is stable. We use these theoretical results to analyze stability of human walking depending on different sensorimotor control gains. The model predicts that control gains should be larger for slower-paced walking, which is partially consistent with the available experimental data.

neuroscience↗

bioRxiv2022

High-level motor planning allows flexible walking at different gait patterns in a neuromechanical model

Humans are able to adopt almost any desired gait pattern on the fly when walking. We postulate that this flexibility in humans is partially due to the ability to control the whole body during walking as a volitional, goal-directed movement that can be planned and changed, rather than having to rely on habitual, reflexive control that is adapted over long time-scales. Here we present a neuromechanical model that accounts for this flexibility by combining movement goals and motor plans on a kinematic task level with low-level spinal feedback loops. We show that the model is able to walk at a wide range of different gait patterns by choosing a small number of high-level control parameters representing a movement goal. A larger number of parameters governing the low-level reflex loops in the spinal cord, on the other hand, remains fixed. We also show that the model is able to generalize the learned behavior by re-combining the high-level control parameters and walk with gait patterns it had not encountered before. Furthermore, the model can transition between different gaits without loss of balance by switching to a new set of control parameters in real time.

neuroscience↗

bioRxiv2021

A Neuromuscular Model of Human Locomotion Combines Spinal Reflex Circuits with Voluntary Movements

Existing models of human walking use low-level reflexes or neural oscillators to generate movement. While appropriate to generate the stable, rhythmic movement patterns of steady-state walking, these models lack the ability to change their movement patterns or spontaneously generate new movements in the specific, goal-directed way characteristic of voluntary movements. Here we present a neuromuscular model of human locomotion that bridges this gap and combines the ability to execute goal directed movements with the generation of stable, rhythmic movement patterns that are required for robust locomotion. The model represents goals for voluntary movements of the swing leg on the task level of swing leg joint kinematics. Smooth movements plans towards the goal configuration are generated on the task level and transformed into descending motor commands that execute the planned movements, using internal models. The movement goals and plans are updated in real time based on sensory feedback and task constraints. On the spinal level, the descending commands during the swing phase are integrated with a generic stretch reflex for each muscle. Stance leg control solely relies on dedicated spinal reflex pathways. Spinal reflexes stimulate Hill-type muscles that actuate a biomechanical model with eight internal joints and six free-body degrees of freedom. The model is able to generate voluntary, goal-directed reaching movements with the swing leg and combine multiple movements in a rhythmic sequence. During walking, the swing leg is moved in a goal-directed manner to a target that is updated in real-time based on sensory feedback to maintain upright balance, while the stance leg is stabilized by low-level reflexes and a behavioral organization switching between swing and stance control for each leg. With this combination of reflex-based stance leg and voluntary, goal-directed control of the swing leg, the model controller generates rhythmic, stable walking patterns in which the swing leg movement can be flexibly updated in real-time to step over or around obstacles.

neuroscience↗

bioRxiv2020

The Effect of a Virtual No-Step Zone on Balance Control in Walking

Humans need to actively control their upright posture during walking to avoid loss of balance. We do not have a comprehensive theory for how humans regulate balance during walking, especially in complex environments. Balance must be maintained in a variety of contexts including crowded city side-walks, rocky nature trails, walks on the beach, or fast-paced sporting events. The nervous system must process many aspects of the environment to produce an appropriate motor output in order to maintain balance on two legs. We have previously identified three balance mechanisms that young healthy adults use to maintain balance while walking: 1) The ankle roll mechanism, a modulation of ankle inversion/eversion; 2) The foot placement mechanism, a shift of the swing foot placement; and 3) The push-off mechanism, a modulation of the ankle plantarflexion angle during double stance. We know that these mechanisms are interdependent and can be influenced by internal factors such as the phase of the gait cycle and walking cadence. Here we seek to determine whether there are changes in neural control of balance when walking in the presence of environmental constraints. Subjects walked on a selfpaced treadmill while immersed in a virtual environment that provides three different colored pathways. Subjects were instructed not to step in the No-Step Zone, which appeared either on the right or left side of the subject. While walking, subjects received balance perturbations in the form of galvanic vestibular stimulation, providing the sensation of falling sideways, either toward the No-Step zone or toward the Neutral zone on the other side. The results indicate that the use of the balance mechanisms are subtly altered depending on whether the perceived fall is toward the No-Step or the Neutral zone. This experiment provides further evidence that the balance control system during walking is extremely flexible, recruiting multiple mechanisms at different times in the gait cycle to adapt to environmental constraints.

neuroscience↗

bioRxiv2019

Walking cadence affects the recruitment of the medial-lateral balance mechanisms

We have previously identified three balance mechanisms that young healthy adults use to maintain balance while walking. The three mechanisms are: 1) The lateral ankle mechanism, an active modulation of ankle inversion/eversion in stance; 2) The foot placement mechanism, an active shift of the swing foot placement; and 3) The push-off mechanism, an active modulation of the ankle plantarflexion angle during double stance. Here we seek to determine whether there are changes in neural control of balance when walking at different cadences and speeds. Twenty-one healthy young adults walked on a self-paced treadmill while immersed in a 3D virtual reality cave, and periodically received balance perturbations (bipolar galvanic vestibular stimulation) eliciting a perceived fall to the side. Subjects were instructed to match two cadences specified by a metronome, 110bpm (High) and 80bpm (Low), which led to faster and slower gait speeds, respectively. The results indicate that subjects altered the use of the balance mechanisms at different cadences. The lateral ankle mechanism was used more in the Low condition, while the foot placement mechanism was used more in the High condition. There was no difference in the use of the push-off mechanism between cadence conditions. These results suggest that neural control of balance is altered when gait characteristics such as cadence change, suggesting a flexible balance response that is sensitive to the constraints of the gait cycle. We speculate that the use of the balance mechanisms may be a factor resulting in well-known characteristics of gait in populations with compromised balance control, such as slower gait speed in older adults or higher cadence in people with Parkinsons disease.

neuroscience↗

bioRxiv2019

Interdependence of balance mechanisms during bipedal locomotion

Our main interest is to identify how humans maintain upright while walking. Balance during standing and walking is different, primarily due to a gait cycle which the nervous system must contend with a variety of body configurations and frequent perturbations (i.e., heel-strike). We have identified three mechanisms that healthy young adults use to respond to a visually perceived fall to the side. The lateral ankle mechanism and the foot placement mechanism are used to shift the center of pressure in the direction of the perceived fall, and the center of mass away from the perceived fall. The push-off mechanism, a systematic change in ankle plan-tarflexion angle in the trailing leg, results in fine adjustments to medial-lateral balance near the end of double stance. The focus here is to understand how the three basic balance mechanisms are coordinated to produce an overall balance response. The results indicate that lateral ankle and foot placement mechanisms are inversely related. Larger lateral ankle responses lead to smaller foot placement changes. Correlations involving the push-off mechanism, while significant, were weak. However, the consistency of the correlations across stimulus conditions suggest the push-off mechanism has the role of small adjustments to medial-lateral movement near the end of the balance response. This verifies that a fundamental feature of human bipedal gait is a highly flexible balance system that recruits and coordinates multiple mechanisms to maintain upright balance during walking to accommodate extreme changes in body configuration and frequent perturbations.

neuroscience↗

bioRxiv2019

The onset time of balance control during walking is phase-independent, but the magnitude of the response is not

The human body is mechanically unstable during walking. Maintaining upright stability requires constant regulation of muscle force by the central nervous system to push against the ground and move the body mass in the desired way. Activation of muscles in the lower body in response to sensory or mechanical perturbations during walking is usually highly phase-dependent, because the effect any specific muscle force has on the body movement depends upon the body configuration. Yet the resulting movement patterns of the upper body after the same perturbations are largely phase-independent. This is puzzling, because any change of upper-body movement must be generated by parts of the lower body pushing against the ground. How do phase-dependent muscle activation patterns along the lower body generate phase-independent movement patterns of the upper body? We hypothesize that in response to a perceived threat to balance, the nervous system generates a functional response by pushing against the ground in any way possible with the current body configuration. This predicts that the changes in the ground reaction force patterns following a balance perturbation should be phase-independent. Here we test this hypothesis by disturbing upright balance using Galvanic vestibular stimulation at three different points in the gait cycle. We measure the resulting changes in whole-body center of mass movement and the location of the center of pressure of the ground reaction force. We find that the whole-body balance response is not phase-independent as expected: balance responses are initiated faster and are smaller following a disturbance late in the gait cycle. Somewhat paradoxically, the initial center of pressure changes are larger for perturbations late in the gait cycle. The onset of the center of pressure changes however, does not depend on the phase of the perturbation. The results partially support our hypothesis of a phase-independent functional balance response underlying the phase-dependent recruitment of different balance mechanisms at different points of the gait cycle. We conclude that the central nervous system recruits any available mechanism to push against the ground to maintain balance as fast as possible in response to a perturbation, but the different mechanisms do not have equal strength.

neuroscience↗