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Biomedical subjects

H L Galiana

Publications and source records attributed to H L Galiana.

At least 19 recordsLinked to original sources

Modelling non-linearities in the vestibulo-ocular reflex (VOR) after unilateral or bilateral loss of peripheral vestibular function.

We recorded the vestibulo-ocular reflex (VOR) in 18 normal subjects, 50 patients with unilateral loss of vestibular function and 18 patients with bilateral loss of vestibular function. The unilateral cases had either partial loss (i.e. vestibular neuronitis or Meniere's disease) or total loss (i.e. vestibular nerve section), whereas bilateral cases had only partial loss (i.e. due to ototoxicity or to suspected microangiopathy, secondary to severe kidney disease). Tests were performed at 1/6-Hz passive head rotation in the dark, with peak head velocities ranging from 125 to 190 degrees/s. We report on the distinct VOR non-linearities observed in unilateral versus bilateral patients: whereas unilateral patients all exhibit an asymmetric hypofunction with decreasing VOR gain at higher head velocities, bilateral patients have a more severe but symmetric hypofunction associated with increasing VOR gain at higher head velocities. We present a model study that can duplicate the nature of these characteristics, based mainly on peripheral non-linear semicircular canal characteristics and secondary central compensation. Theoretical analyses point to the importance of clinical test parameters (rotation speed and frequency) in the determination of a functional VOR and the detection of reflex non-linearities, so that test protocols can seriously bias the evaluation of adequate functional recovery.

Afferent Pathways↗

Comparing extraocular motoneuron discharges during head-restrained saccades and head-unrestrained gaze shifts.

Burst neurons (BNs) in the paramedian pontine reticular formation provide the primary input to the extraocular motoneurons (MNs) during head-restrained saccades and combined eye-head gaze shifts. Prior studies have shown that BNs carry eye movement-related signals during saccades and carry head as well as eye movement-related signals during gaze shifts. Therefore MNs receive signals related to head motion during gaze shifts, yet they solely drive eye motion. Here we addressed whether the relationship between MN firing rates and eye movements is influenced by the additional premotor signals present during gaze shifts. Neurons in the abducens nucleus of monkeys were first studied during saccades made with the head stationary. We then recorded from the same neurons during voluntary combined eye-head gaze shifts. We conclude that the activity of MNs, in contrast to that of BNs, is related to eye motion by the same dynamic relationship during head-restrained saccades and head-unrestrained gaze shifts. In addition, we show that a standard metric-based analysis [i.e., counting the number of spikes (NOS) in a burst] yields misleading results when applied to the same data set. We argue that this latter approach fails because it does not properly consider the system's dynamics or the strong interactions between eye and head motion.

Animals↗

Complex podokinetic (PK) response to post-rotational vestibular stimulation.

Recent studies identified an adaptive "Podokinetic" (PK) sensory motor system involved in sensing and controlling spatial orientation during locomotion, by referencing body orientation to the space-stable stance foot. This paper investigates the interaction of vestibular and PK systems by asking blindfolded subjects to 'step-in-place' (i.e. without turning) after exposing them to a unidirectional post-rotational vestibular stimulus. Six of the nine subjects consistently began by vigorously propelling themselves round in the direction of preceding turntable rotation, but notably without any sensation of turning. In all these subjects the speed of this PK-induced rotation progressively declined to zero over about the next 30 sec and then reversed direction with increasing speed for about 50 sec. Thereafter the speed of rotation declined slowly to zero over the next 4 to 5 minutes. Since the PK-generated body rotation presumably feeds back into the vestibular-PK drive, we formulated a closed loop model of the combined system to investigate the complex nature of the behavioral response. The simulated response of this model closely resembled the experimental data, suggesting that there is indeed a functionally closed loop operating between the vestibular and podokinetic systems in natural life.

Adult↗

Vestibular adaptation: how models can affect data interpretations.

Vestibular adaptation can be induced optically or by chemical or physical injury to the vestibular apparatus or the brain stem. In searching for the sites or mechanisms of vestibular adaptation, neurophysiologists often rely on comparing central resting (background) activities and central modulations (sensitivity) during vestibular stimulation, before and after motor learning or vestibular compensation. It is assumed that adapted central sites must exhibit modulation changes that parallel vestibulo-ocular reflex changes. Using model simulations and analysis, we will show that such presumptions may be misleading. First, using a simple schematic of interconnected cells or nuclei, one can show that modulation depth and background "tone" can be modified (or fixed) independently, using weightings on direct or indirect afferent projections. That is, if synaptic weights along all stimulus pathways are altered, one may fix or strongly modify central premotor characteristics in a manner apparently unrelated to global reflex changes. In the vestibulo-ocular reflex, the dominant premotor pathways contain position-vestibular-pause cells and eye-head-velocity cells (which are behaviorally similar to floccular-target neurons). Several experiments have reported negligible changes in the velocity sensitivity of position-vestibular-pause cells, despite large gain changes in the vestibulo-ocular reflex induced by training with visual-vestibular conflict. On the other hand, the modulation changes on floccular-target neurons (position-vestibular-pause) can be much larger than the changes in reflex gain. Using a bilateral vestibulo-ocular reflex model, we show that overall increases or decreases in reflex gain can be expressed (even overexpressed) in one particular subgroup of premotor neurons. Nevertheless, such observations are theoretically compatible with synaptic changes on all primary projections in a widely interconnected central network. Hence, stable neural responses during reflex adaptation are not sufficient to exclude a potential site of sensory-motor adaptation. Similarly, modified neural responses (as in cerebellum) need not necessarily imply a direct role in supporting the adapted state. Model predictions should help to design additional experimental protocols, to test hypotheses, and to refine diagnostic measures of recovery after vestibular lesions.

Adaptation, Physiological↗

Hypothesis for shared central processing of canal and otolith signals.

A common goal of the translational vestibuloocular reflex (TVOR) and the rotational vestibuloocular reflex (RVOR) is to stabilize visual targets on the retinae during head movement. However, these reflexes differ significantly in their dynamic characteristics at both sensory and motor levels, implying a requirement for different central processing of canal and otolith signals. Semicircular canal afferents carry a signal proportional to angular head velocity, whereas primary otolith afferents modulate approximately in phase with linear head acceleration. Behaviorally, the RVOR exhibits a robust response down to approximately 0.01 Hz, yet the TVOR is only significant above approximately 0.5 Hz. Several hypotheses were proposed to address central processing in the TVOR pathways. All rely on a central filtering process that precedes a "neural integrator" shared with the RVOR. We propose an alternative hypothesis for the convergence of canal and otolith signals that does not impose the requirement for additional low-pass filters for the TVOR. The approach is demonstrated using an anatomically based, simple model structure that reproduces the general dynamic characteristics of the RVOR and TVOR at both ocular and central levels. Differential dynamic processing of otolith and canal signals is achieved by virtue of the location at which sensory information enters a shared but distributed neural integrator. As a result, only the RVOR is provided with compensation for the eye plant. Hence canal and otolith signals share a common central integrator, as in previous hypotheses. However, we propose that the required additional filtering of otolith signals is provided by the eye plant.

Animals↗

The use of system identification techniques in the analysis of oculomotor burst neuron spike train dynamics.

The objective of system identification methods is to construct a mathematical model of a dynamical system in order to describe adequately the input-output relationship observed in that system. Over the past several decades, mathematical models have been employed frequently in the oculomotor field, and their use has contributed greatly to our understanding of how information flows through the implicated brain regions. However, the existing analyses of oculomotor neural discharges have not taken advantage of the power of optimization algorithms that have been developed for system identification purposes. In this article, we employ these techniques to specifically investigate the "burst generator" in the brainstem that drives saccadic eye movements. The discharge characteristics of a specific class of neurons, inhibitory burst neurons (IBNs) that project monosynaptically to ocular motoneurons, are examined. The discharges of IBNs are analyzed using different linear and nonlinear equations that express a neuron's firing frequency and history (i.e., the derivative of frequency), in terms of quantities that describe a saccade trajectory, such as eye position, velocity, and acceleration. The variance accounted for by each equation can be compared to choose the optimal model. The methods we present allow optimization across multiple saccade trajectories simultaneously. We are able to investigate objectively how well a specific equation predicts a neuron's discharge pattern as well as whether increasing the complexity of a model is justifiable. In addition, we demonstrate that these techniques can be used both to provide an objective estimate of a neuron's dynamic latency and to test whether a neuron's initial firing rate (expressed as an initial condition) is a function of a quantity describing a saccade trajectory (such as initial eye position).

Action Potentials↗

A bilateral model integrating vergence and the vestibulo-ocular reflex.

The majority of previous modelling studies of vergence and the vestibulo-ocular reflex (VOR) have postulated arbitrary structures mainly on the basis of input-output behavioural relationships. Such models were developed following traditional schemes of oculomotor organization, based upon the notion of independence between different oculomotor subsystems. This impedes the simulation of complex binocular interactions and associated central activities. In contrast to preceding studies, the mathematical model for binocular control presented here was developed fully on physiological and anatomical grounds which reflect the organization and functional properties of known vergence and VOR premotor centres. Computer simulations show the model properly simulates the main observed characteristics in the discharge of several premotor and motor nuclei during slow vergence and the VOR in the dark. In particular, the model reproduces the activity profiles of abducens internuclear neurons, secondary vestibular cells, tonic prepositus hypoglossi neurons and ocular motoneurons during vergence and the VOR. It also simulates the activity of mesencephalic neurons whose discharge is modulated by vergence parameters alone. It is shown that given recent neurophysiological and behavioural findings, ocular reflexes cannot be properly modelled as separate independent subsystems whereas a single, unified modelling approach can produce results consistent with observed data. This study also shows how changes in the functional activity of shared pathways in a single two-sided structure produce vergence and conjugate integrators whose function relies on coupled loops across the brainstem: separate, dedicated operators are not necessary to replicate data. This provides evidence that challenges previous studies supporting the existence of separate vergence and conjugate integrators to transform velocity to position signals in the brainstem. A major implication of this study is that it questions the validity of testing conjugate and vergence systems independently, neglecting potential interactions.

Computer Simulation↗

Providing distinct vergence and version dynamics in a bilateral oculomotor network.

Given reported interactions between vergence and version dynamics, ocular reflexes cannot be properly modelled as separate independent subsystems. Using a model structure compatible with known anatomy, we show that a single bilateral system can produce results consistent with observed data both at the central and ocular levels. This model provides for both vergence and conjugate integrators in a single controller, and explains the observed modulation on abducens interneurons and mesencephalic vergence cells during vergence responses. Reported interactions between version and vergence would then be a natural consequence of a shared premotor network. Major implications include: the need to record both eyes in a protocol, since cross-talk is always possible; and adaptation to monocular changes could be distributed in all motor projections to both eyes.

Abducens Nerve↗

Vestibulo-ocular reflex (VOR) biases in normal subjects and patients with compensated vestibular loss.

The properties of the vestibulo-ocular reflex (VOR) were examined during sinusoidal passive head rotation in the dark at 1/6 Hz, in 9 normal subjects and 14 unilateral vestibular patients. Rotation speeds ranged from 90 to 180 degrees/s. The bias (offset of slow-phase velocity from zero) and gain in the VOR were estimated by using a polynomial (cubic) fit between head and slow-phase eye velocity, thereby allowing for possible non-linearities in the reflex. The gain in the VOR in this context refers to the linear components of the fit, and so predicts sensitivity only at low head velocities. The aim of the study was to verify previous theoretical predictions that VOR bias could vary with the rotation parameters, that this bias could be used to detect the side of a vestibular lesion even at low frequency rotation, and make non-linearities more obvious. Confirming these predictions, the VOR bias in a given test is never equal to any spontaneous nystagmus, even if present before rotation. The range of values for the gain in the VOR (as defined above) in normals and compensated unilateral vestibular patients overlap, so that they cannot be statistically separated into two response sets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparison of linear vs. non-linear methods for analysing the vestibulo-ocular reflex (VOR).

The vestibulo-ocular reflex (VOR) is traditionally evaluated by the gain (sensitivity) and offset (bias) of nystagmus slow phases during sinusoidal, passive, head rotation in the dark. The analysis methods used are typically only truly applicable to linear systems, but are widely used despite the fact that the VOR has been known to be non-linear since the 19th century. We show here that the parameters obtained by linear methods, with data derived from a non-linear system, can be very noisy and unreliable. The questions are: under what conditions can linear approximations be tolerated, or justified, and can an analysis approach be devised which inherently tolerates non-linearities? Using both simulated and experimental data, it is found that assuming linear analysis methods can produce variable VOR gains and erroneous estimates of the VOR bias. changing with the selected oscillation protocol. Examples of' parameter distortions in bias and VOR gain are first given using simulated data relating slow phase eye velocity to head velocity, at different peak velocities. The relevance of these distortions is then illustrated with selected examples from a database of recordings on normals and unilateral vestibular patients, during rotations in the dark 1/6 Hz and maximum speeds of 90 to 180 degrees/s. More consistent estimates of the gain and bias can be found by properly correcting for phase differences between head and eve velocity, and allowing for non-linear reflex properties. Special indices are suggested to decide whether a particular subject's VOR should be considered non-linear, in order to select the appropriate representation in each case, before estimating VOR characteristics. Selecting the appropriate model (linear or non-linear) will contribute to a better unmasking of parametric trends in the VOR, when comparing normal vs. acute-lesioned subjects, or acute vs, compensated patients. These results have many implications for the design of clinical vestibular protocols and in the evaluation of patient functional deficits.

Computer Simulation↗

Effect of muscimol microinjections into the prepositus hypoglossi and the medial vestibular nuclei on cat eye movements.

1. For horizontal eye movements, previous observations led to the hypothesis that the legendary neural integrator necessary for correct gaze holding, adequate vestibuloocular reflex (VOR), and optokinetic nystagmus, was located in the region of the complex formed by the nucleus prepositus hypoglossi (NPH) and the medial vestibular nucleus (MVN). 2. The aim of the present study was to test the respective contributions of the NPH, of the rostral part of the MVN, which contains most second-order vestibular neurons, and of the central part of the MVN to the horizontal integrator. 3. An injection of muscimol was used to inactivate each of these three zones in the cat's brain. Muscimol is a gamma-aminobutyric acid (GABA) agonist. By binding to GABAA receptors, it induces a hyperpolarization of the neurons that nullifies their activity. Muscimol was injected into the brain stem of the alert cat through a micropipette by an air pressure system. 4. The search coil technique was used to record spontaneous eye movements and the VOR induced by rotating a turntable at a constant velocity. VOR was analyzed by a new method: transient analysis of vestibular nystagmus. 5. A unilateral injection of muscimol into the NPH induced a bilateral gaze-holding failure: saccades were followed by a centripetal postsaccadic drift. A vestibular imbalance was also present but it was moderate and variable. The VOR responses were distorted drastically. Through transient analysis of vestibular nystagmus, that distortion was revealed to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator. The responses to a rotation either toward the injected side or in the opposite direction were asymmetrical. The direction of that asymmetry was variable. 6. A unilateral injection of muscimol into the rostral part of the MVN caused a vestibular imbalance: in complete darkness, a nystagmus appeared, whose linear slow phases were directed toward the side of injection. 7. A unilateral injection of muscimol into the central part of the MVN induced a syndrome where a severe bilateral gaze-holding failure was combined with a vestibular imbalance. In the light, saccades were followed by a bilateral centripetal postsaccadic drift. In complete darkness, a nystagmus was observed, whose curved slow phases were directed towards the side of injection. The VOR responses were distorted drastically. Here again, that distortion was revealed by our analysis to be due more to a failure of the neural integrator than to an alteration of the vestibular input to the neural integrator.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Transient analysis of vestibular nystagmus.

The significance of a nystagmus-dependent, transient component in the overall slow-phase response of the vestibulo-ocular reflex (VOR) is brought into focus. First, a simulated example is presented that shows how this transient component can bias current algorithms for the estimation of VOR parameters. Second, new algorithms are proposed that are able to estimate VOR parameters regardless of the presence of transients. Third, the new algorithms are applied to experimental data, and the results are compared with those from current algorithms. The results clearly show that the transient component can significantly alter the apparent VOR time constant, particularly when the reflex has been lesioned. The algorithms open new areas of research on the possible role of nystagmus in enhancing the compensatory function of the VOR.

Algorithms↗

Evaluation of three template matching algorithms for registering images of the eye.

The purpose of this paper is to evaluate the ability of three similarity measures to register a template in a sequence of near-infrared eye images. Three measures are evaluated: the normalized correlation coefficient (rho), the sum of absolute valued differences (SAVD), and a relatively new technique based on a sign change criterion, called the stochastic sign change criterion (SSC). Performance is measured in terms of the method's ability to track the pupil center derived from fitting a general 2-D ellipse to the pupil contour. Experiments using static eye images indicate that rho is not a reliable similarity measure. Conversely, both SAVD and SSC show enough potential to merit an investigation into their performance in tracking dynamic eye movements. It is anticipated that SAVD and SSC can accommodate a range of eye movements spanning at least 60 degrees horizontally and 40 degrees vertically.

Algorithms↗

The role of structural symmetry in linearizing ocular reflexes.

This work presents a simulation study using an anatomically relevant model of the vestibulo-ocular reflex (VOR). The aim is to explore the functional properties of a bilateral structure in the premotor circuits of the oculomotor system. The major conclusions using sinusoidal inputs are: A bilateral structure in a sensory-motor system improves its linear range beyond expected central limits, if provided with symmetric interconnections. Given a bilateral (push-pull) sensory arrangement, non-linear sensor characteristics are actually advantageous. The greatest improvement in linear range of the reflex (here VOR) relies on intact sensors on both sides. In the case of a single sensor (unilateral head velocity input), or unmatched bilateral sensors, this study predicts a decrease in the linear range and the appearance of a variable bias. These implications are compatible with available data and can be tested in a clinical environment.

Animals↗

Parametric classification of segments in ocular nystagmus.

A new method for nystagmus classification, using system identification techniques, is presented. We formulate a system whose input is head position and whose output is eye position. We approximate this system with an autoregressive with exogenous input (ARX) model which relates the input and output (transfer function) regardless of the temporal profile for the sensory stimulation. The system is then identified using a least squares criteria and three indicators are produced. From these a flag is produced that marks slow and fast phases as well as blinks and bad data segments. Tests with simulated and real data are presented and indicate that the segment classification is remarkably insensitive to recording noise and that it is more robust than previous techniques. Operator intervention is minimal. We expect the method to be applicable for all types of ocular nystagmus. Here, however, we illustrate our results only in the context of the vestibuloocular reflex (VOR). A discussion explains how this method can also be applied for optokinetic (OKN) or pursuit nystagmus.

Algorithms↗