A model-based theory on the origin of downbeat nystagmus

The pathomechanism of downbeat nystagmus (DBN), an ocular motor sign typical for vestibulo-cerebellar lesions, remains unclear. Previous hypotheses conjectured various deficits such as an imbalance of central vertical vestibular or smooth pursuit pathways to be causative for the generation of spontaneous upward drift. However, none of the previous theories explains the full range of ocular motor deficits associated with DBN, i.e., impaired vertical smooth pursuit (SP), gaze evoked nystagmus, and gravity dependence of the upward drift. We propose a new hypothesis, which explains the ocular motor signs of DBN by damage of the inhibitory vertical gaze-velocity sensitive Purkinje cells (PCs) in the cerebellar flocculus (FL). These PCs show spontaneous activity and a physiological asymmetry in that most of them exhibit downward on-directions. Accordingly, a loss of vertical floccular PCs will lead to disinhibition of their brainstem target neurons and, consequently, to spontaneous upward drift, i.e., DBN. Since the FL is involved in generation and control of SP and gaze holding, a single lesion, e.g., damage to vertical floccular PCs, may also explain the associated ocular motor deficits. To test our hypothesis, we developed a computational model of vertical eye movements based on known ocular motor anatomy and physiology, which illustrates how cortical, cerebellar, and brainstem regions interact to generate the range of vertical eye movements seen in healthy subjects. Model simulation of the effect of extensive loss of floccular PCs resulted in ocular motor features typically associated with cerebellar DBN: (1) spontaneous upward drift due to decreased spontaneous PC activity, (2) gaze evoked nystagmus corresponding to failure of the cerebellar loop supporting neural integrator function, (3) asymmetric vertical SP deficit due to low gain and asymmetric attenuation of PC firing, and (4) gravity-dependence of DBN caused by an interaction of otolith-ocular pathways with impaired neural integrator functio

Vestibular Perception following Acute Unilateral Vestibular Lesions.

Little is known about the vestibulo-perceptual (VP) system, particularly after a unilateral vestibular lesion. We investigated vestibulo-ocular (VO) and VP function in 25 patients with vestibular neuritis (VN) acutely (2 days after onset) and after compensation (recovery phase, 10 weeks). Since the effect of VN on reflex and perceptual function may differ at threshold and supra-threshold acceleration levels, we used two stimulus intensities, acceleration steps of 0.5°/s(2) and velocity steps of 90°/s (acceleration 180°/s(2)). We hypothesised that the vestibular lesion or the compensatory processes could dissociate VO and VP function, particularly if the acute vertiginous sensation interferes with the perceptual tasks. Both in acute and recovery phases, VO and VP thresholds increased, particularly during ipsilesional rotations. In signal detection theory this indicates that signals from the healthy and affected side are still fused, but result in asymmetric thresholds due to a lesion-induced bias. The normal pattern whereby VP thresholds are higher than VO thresholds was preserved, indicating that any 'perceptual noise' added by the vertigo does not disrupt the cognitive decision-making processes inherent to the perceptual task. Overall, the parallel findings in VO and VP thresholds imply little or no additional cortical processing and suggest that vestibular thresholds essentially reflect the sensitivity of the fused peripheral receptors. In contrast, a significant VO-VP dissociation for supra-threshold stimuli was found. Acutely, time constants and duration of the VO and VP responses were reduced - asymmetrically for VO, as expected, but surprisingly symmetrical for perception. At recovery, VP responses normalised but VO responses remained shortened and asymmetric. Thus, unlike threshold data, supra-threshold responses show considerable VO-VP dissociation indicative of additional, higher-order processing of vestibular signals. We provide evidence of perceptual processes (ultimately cortical) participating in vestibular compensation, suppressing asymmetry acutely in unilateral vestibular lesions

Frequency-Domain Analysis of Intrinsic Neuronal Properties using High-Resistant Electrodes

Intrinsic cellular properties of neurons in culture or slices are usually studied by the whole cell clamp method using low-resistant patch pipettes. These electrodes allow detailed analyses with standard electrophysiological methods such as current- or voltage-clamp. However, in these preparations large parts of the network and dendritic structures may be removed, thus preventing an adequate study of synaptic signal processing. Therefore, intact in vivo preparations or isolated in vitro whole brains have been used in which intracellular recordings are usually made with sharp, high-resistant electrodes to optimize the impalement of neurons. The general non-linear resistance properties of these electrodes, however, severely limit accurate quantitative studies of membrane dynamics especially needed for precise modelling. Therefore, we have developed a frequency-domain analysis of membrane properties that uses a Piece-wise Non-linear Electrode Compensation (PNEC) method. The technique was tested in second-order vestibular neurons and abducens motoneurons of isolated frog whole brain preparations using sharp potassium chloride- or potassium acetate-filled electrodes. All recordings were performed without online electrode compensation. The properties of each electrode were determined separately after the neuronal recordings and were used in the frequency-domain analysis of the combined measurement of electrode and cell. This allowed detailed analysis of membrane properties in the frequency-domain with high-resistant electrodes and provided quantitative data that can be further used to model channel kinetics. Thus, sharp electrodes can be used for the characterization of intrinsic properties and synaptic inputs of neurons in intact brains

Serving performance in a suprapostural visual signal detection task: context-dependent and direction-specific control of body sway with fingertip light touch

Keeping gaze fixed on a target during visual smooth pursuit or touch light during fingertip contact while standing may resemble the goals of a suprapostural task with the implicit demands to minimize self-imposed sensorimotor variability. To test whether the principle of a suprapostural task generalizes to more complex sensorimotor stimulus-response mappings, we investigated how the control of body sway is influenced by an implicit feedback coupling (IFC) between the variability of touch forces at the contact point and perceptual difficulty, that is vertical jitter of a horizontally oscillating Landolt-C, in a visual signal detection task (VSDT). Mediolateral (ML) body sway of ten young healthy adults was assessed in four IFC conditions: (1) LT with independent jitter (LT-IJ), (2) LT with jitter depending on LT contact force (LT-CF), (3) LT with jitter depending on body sway (LT-BS), and (4) no contact with jitter depending on body sway (NT-BS). We assumed that the postural control system would be responsive to IFC and therefore reduce body sway in both IFC conditions. Resulting mediolateral body sway differed between the IFC conditions. Reduced sway was found in LT-CF and LT-BS compared to LT-IJ and in LT-BS compared to NT-BS. Our results demonstrate that processes controlling body sway can reduce postural variability below a variability level achieved by LT augmentation of body sway-related feedback alone. Both direct (LT-CF) and indirect (LT-BS) IFC involvement of fingertip contact minimized sway, which implies that no hierarchy existed for whole body sway or precision of fingertip contact (integration of both control processes) or that they can be reversed flexibly (one facilitating the other) if it serves the implicit goal of reduced perceptual noise and enhanced performance within the context of our suprapostural VSDT

The Healthcare Benefits and Impact of Artificial Intelligence Applications on Behaviour of Healthcare Users: A Structured Review of Primary Literature

Introduction: Artificial intelligence (AI) is one of the most considered topics of the current time. AI has the power to bring revolutionary improvements to the world of technology not only in the field of computer science but also in other fields like medical sciences. Objectives: This paper assumes the adoption of appropriate AI engineering principals in previous studies, and focusses on providing a structured review of the impact of AI on human society and the individual human being as a technology user. Additionally, it opens a window on how the future will look like in terms of AI and personalised medicine. Methods: The paper employed a qualitative research approach and data were collected through a structured literature review. Twenty-three peer reviewed papers were identified and analysed in relation to their relevance to the study. Results: Previous studies show a positive impact on users' behaviour is expected in supporting their healthcare needs especially in decision-making, personalised treatment and future diseases prediction, and that integrating users in studying AI impact is essential to test possible implications of the technology. Conclusion: Results indicate that without a clear understanding of why patients need AI, or how AI can support individuals with their healthcare needs, it is difficult to visualise the kinds of AI applications that have a meaningful and sustainable impact the daily lives of individuals. Therefore, there is an emerging need to understand the impact of AI technology on users' behaviour to maximise the potential benefits of AI technology

Cognitive loading affects motor awareness and movement kinematics but not locomotor trajectories during goal-directed walking in a virtual reality environment.

The primary purpose of this study was to investigate the effects of cognitive loading on movement kinematics and trajectory formation during goal-directed walking in a virtual reality (VR) environment. The secondary objective was to measure how participants corrected their trajectories for perturbed feedback and how participants' awareness of such perturbations changed under cognitive loading. We asked 14 healthy young adults to walk towards four different target locations in a VR environment while their movements were tracked and played back in real-time on a large projection screen. In 75% of all trials we introduced angular deviations of ±5° to ±30° between the veridical walking trajectory and the visual feedback. Participants performed a second experimental block under cognitive load (serial-7 subtraction, counter-balanced across participants). We measured walking kinematics (joint-angles, velocity profiles) and motor performance (end-point-compensation, trajectory-deviations). Motor awareness was determined by asking participants to rate the veracity of the feedback after every trial. In-line with previous findings in natural settings, participants displayed stereotypical walking trajectories in a VR environment. Our results extend these findings as they demonstrate that taxing cognitive resources did not affect trajectory formation and deviations although it interfered with the participants' movement kinematics, in particular walking velocity. Additionally, we report that motor awareness was selectively impaired by the secondary task in trials with high perceptual uncertainty. Compared with data on eye and arm movements our findings lend support to the hypothesis that the central nervous system (CNS) uses common mechanisms to govern goal-directed movements, including locomotion. We discuss our results with respect to the use of VR methods in gait control and rehabilitation

Quantification of Head Movement Predictability and Implications for Suppression of Vestibular Input during Locomotion

Achieved motor movement can be estimated using both sensory and motor signals. The value of motor signals for estimating movement should depend critically on the stereotypy or predictability of the resulting actions. As predictability increases, motor signals become more reliable indicators of achieved movement, so weight attributed to sensory signals should decrease accordingly. Here we describe a method to quantify this predictability for head movement during human locomotion by measuring head motion with an inertial measurement unit (IMU), and calculating the variance explained by the mean movement over one stride, i.e., a metric similar to the coefficient of determination. Predictability exhibits differences across activities, being most predictable during running, and changes over the course of a stride, being least predictable around the time of heel-strike and toe-off. In addition to quantifying predictability, we relate this metric to sensory-motor weighting via a statistically optimal model based on two key assumptions: (1) average head movement provides a conservative estimate of the efference copy prediction, and (2) noise on sensory signals scales with signal magnitude. The model suggests that differences in predictability should lead to changes in the weight attributed to vestibular sensory signals for estimating head movement. In agreement with the model, prior research reports that vestibular perturbations have greatest impact at the time points and during activities where high vestibular weight is predicted. Thus, we propose a unified explanation for time-and activity-dependent modulation of vestibular effects that was lacking previously. Furthermore, the proposed predictability metric constitutes a convenient general method for quantifying any kind of kinematic variability. The probabilistic model is also general; it applies to any situation in which achieved movement is estimated from both motor signals and zero-mean sensory signals with signal-dependent noise

Eye Movements Affect Postural Control in Young and Older Females

Visual information is used for postural stabilization in humans. However, little is known about how eye movements prevalent in everyday life interact with the postural control system in older individuals. Therefore, the present study assessed the effects of stationary gaze fixations, smooth pursuits, and saccadic eye movements, with combinations of absent, fixed and oscillating large-field visual backgrounds to generate different forms of retinal flow, on postural control in healthy young and older females. Participants were presented with computer generated visual stimuli, whilst postural sway and gaze fixations were simultaneously assessed with a force platform and eye tracking equipment, respectively. The results showed that fixed backgrounds and stationary gaze fixations attenuated postural sway. In contrast, oscillating backgrounds and smooth pursuits increased postural sway. There were no differences regarding saccades. There were also no differences in postural sway or gaze errors between age groups in any visual condition. The stabilizing effect of the fixed visual stimuli show how retinal flow and extraocular factors guide postural adjustments. The destabilizing effect of oscillating visual backgrounds and smooth pursuits may be related to more challenging conditions for determining body shifts from retinal flow, and more complex extraocular signals, respectively. Because the older participants matched the young group's performance in all conditions, decreases of posture and gaze control during stance may not be a direct consequence of healthy aging. Further research examining extraocular and retinal mechanisms of balance control and the effects of eye movements, during locomotion, is needed to better inform fall prevention interventions

An Inverse Optimal Control Approach to Explain Human Arm Reaching Control Based on Multiple Internal Models

Human motor control is highly efficient in generating accurate and appropriate motor behavior for a multitude of tasks. This paper examines how kinematic and dynamic properties of the musculoskeletal system are controlled to achieve such efficiency. Even though recent studies have shown that the human motor control relies on multiple models, how the central nervous system (CNS) controls this combination is not fully addressed. In this study, we utilize an Inverse Optimal Control (IOC) framework in order to find the combination of those internal models and how this combination changes for different reaching tasks. We conducted an experiment where participants executed a comprehensive set of free-space reaching motions. The results show that there is a trade-off between kinematics and dynamics based controllers depending on the reaching task. In addition, this trade-off depends on the initial and final arm configurations, which in turn affect the musculoskeletal load to be controlled. Given this insight, we further provide a discomfort metric to demonstrate its influence on the contribution of different inverse internal models. This formulation together with our analysis not only support the multiple internal models (MIMs) hypothesis but also suggest a hierarchical framework for the control of human reaching motions by the CNS

Somatosensory Influence on Platform-Induced Translational Vestibulo-Ocular Reflex in Vertical Direction in Humans

The vestibulo-ocular reflex (VOR) consists of two components, the rotational VOR (rVOR) elicited by semicircular canal signals and the translational VOR (tVOR) elicited by otolith signals. Given the relevant role of the vertical tVOR in human walking, this study aimed at measuring the time delay of eye movements in relation to whole-body vertical translations in natural standing position. Twenty (13 females and 7 males) healthy, young subjects (mean 25 years) stood upright on a motor-driven platform and were exposed to sinusoidal movements while fixating a LED, positioned at a distance of 50 cm in front of the eyes. The platform motion induced a vertical translation of 2.6 cm that provoked counteracting eye movements similar to self-paced walking. The time differences between platform and eye movements indicated that the subject's timing of the extraocular motor reaction depended on stimulus frequency and number of repetitions. At low stimulus frequencies (<0.8 Hz) and small numbers of repetitions (<3), eye movements were phase advanced or in synchrony with platform movements. At higher stimulus frequencies or continuous stimulation, eye movements were phase lagged by ~40 ms. Interestingly, the timing of eye movements depended on the initial platform inclination. Starting with both feet in dorsiflexion, eye movements preceded platform movements by 137 ms, whereas starting with both feet in plantar flexion eye movement precession was only 19 ms. This suggests a remarkable influence of foot proprioceptive signals on the timing of eye movements, indicating that the dynamics of the vertical tVOR is controlled by somatosensory signals