Assessing perceptual chromatic equiluminance using a reflexive pupillary response.

Equiluminant stimuli help assess the integrity of colour perception and the relationship of colour to other visual features. As a result of individual variation, it is necessary to calibrate experimental visual stimuli to suit each individual's unique equiluminant ratio. Most traditional methods rely on training observers to report their subjective equiluminance point. Such paradigms cannot easily be implemented on pre-verbal or non-verbal observers. Here, we present a novel Pupil Frequency-Tagging Method (PFTM) for detecting a participant's unique equiluminance point without verbal instruction and with minimal training. PFTM analyses reflexive pupil oscillations induced by slow (< 2 Hz) temporal alternations between coloured stimuli. Two equiluminant stimuli will induce a similar pupil dilation response regardless of colour; therefore, an observer's equiluminant point can be identified as the luminance ratio between two colours for which the oscillatory amplitude of the pupil at the tagged frequency is minimal. We compared pupillometry-based equiluminance ratios to those obtained with two established techniques in humans: minimum flicker and minimum motion. In addition, we estimated the equiluminance point in non-human primates, demonstrating that this new technique can be successfully employed in non-verbal subjects.

Behavioural responses to a photovoltaic subretinal prosthesis implanted in non-human primates.

Retinal dystrophies and age-related macular degeneration related to photoreceptor degeneration can cause blindness. In blind patients, although the electrical activation of the residual retinal circuit can provide useful artificial visual perception, the resolutions of current retinal prostheses have been limited either by large electrodes or small numbers of pixels. Here we report the evaluation, in three awake non-human primates, of a previously reported near-infrared-light-sensitive photovoltaic subretinal prosthesis. We show that multipixel stimulation of the prosthesis within radiation safety limits enabled eye tracking in the animals, that they responded to stimulations directed at the implant with repeated saccades and that the implant-induced responses were present two years after device implantation. Our findings pave the way for the clinical evaluation of the prosthesis in patients affected by dry atrophic age-related macular degeneration.

A Theory for Sparse Event-Based Closed Loop Control.

Most dynamic systems are controlled by discrete time controllers. One of the main challenges faced during the design of a digital control law is the selection of the appropriate sampling time. A small sampling time will increase the accuracy of the controlled output at the expense of heavy computations. In contrast, a large sampling time will decrease the computational power needed to update the control law at the expense of a smaller stability region. In addition, once the setpoint is reached, the controlled input is still updated, making the overall controlled system not energetically efficient. To be more efficient, one can update the control law based on a significant fixed change of the controlled signal (send-on-delta or event-based controller). Like for time-based discretization, the amplitude of the significant change must be chosen carefully to avoid oscillations around the setpoint (e.g., if the setpoint is in between two samples) or an unnecessary increase of the samples number needed to reach the setpoint with a given accuracy. This paper proposes a novel non-linear event-based discretization method based on inter-events duration. We demonstrate that our new method reaches an arbitrary accuracy independently of the setpoint amplitude without increasing the network data transmission bandwidth. The method decreases the overall number of samples needed to estimate the states of a dynamical system and the update rate of an actuator, making it more energetically efficient.

Transcranial ultrasonic stimulation modulates single-neuron discharge in macaques performing an antisaccade task.

BACKGROUND: Low intensity transcranial ultrasonic stimulation (TUS) has been demonstrated to non-invasively and transiently stimulate the nervous system. Although US neuromodulation has appeared robust in rodent studies, the effects of US in large mammals and humans have been modest at best. In addition, there is a lack of direct recordings from the stimulated neurons in response to US. Our study investigates the magnitude of the US effects on neuronal discharge in awake behaving monkeys and thus fills the void on both fronts. OBJECTIVE/HYPOTHESIS: In this study, we demonstrate the feasibility of recording action potentials in the supplementary eye field (SEF) as TUS is applied simultaneously to the frontal eye field (FEF) in macaques performing an antisaccade task. RESULTS: We show that compared to a control stimulation in the visual cortex, SEF activity is significantly modulated shortly after TUS onset. Among all cell types 40% of neurons significantly changed their activity after TUS. Half of the neurons showed a transient increase of activity induced by TUS. CONCLUSION: Our study demonstrates that the neuromodulatory effects of non-invasive focused ultrasound can be assessed in real time in awake behaving monkeys by recording discharge activity from a brain region reciprocally connected with the stimulated region. The study opens the door for further parametric studies for fine-tuning the ultrasonic parameters. The ultrasonic effect could indeed be quantified based on the direct measurement of the intensity of the modulation induced on a single neuron in a freely performing animal. The technique should be readily reproducible in other primate laboratories studying brain function, both for exploratory and therapeutic purposes and to facilitate the development of future clinical TUS devices.

Inaccurate Saccades and Enhanced Vestibulo-Ocular Reflex Suppression during Combined Eye-Head Movements in Patients with Chronic Neck Pain: Possible Implications for Cervical Vertigo.

BACKGROUND: The primate ocular motor system is designed to acquire peripheral targets of interest by coordinating visual, vestibular, and neck muscle activation signals. The vestibulo-ocular reflex (VOR) is greatly reduced at the onset of large eye-head (gaze) saccades and resumes before the end of the saccades to stabilize eye-in-orbit and ensure accurate target acquisition. Previous studies have relied on manipulating head movements in normal individuals to study VOR suppression and gaze kinematics. We sought to determine if reduced head-on-trunk movement alters VOR suppression and gaze accuracy similar to experiments involving normal subjects and if intentionally increasing head and neck movement affects these dynamics. METHODS: We measured head and gaze movements using magnetic search coil oculography in eight patients with cervical soft tissue disorders and seven healthy subjects. All participants made horizontal head-free saccades to acquire a laser dot target that stepped pseudorandomly 30-65° to either side of orbital mid-position, first using typical head and eye movements and again after being instructed to increase head amplitudes as much as possible. RESULTS: Compared to healthy subjects, patients made smaller head movements that contributed only 6% to total gaze saccade amplitudes. Head movements were also slowed, prolonged, and delayed. VOR suppression was increased and prolonged. Gaze saccades were inaccurate and delayed with long durations and decreased peak velocities. CONCLUSION: In patients with chronic neck pain, the internal commands issued for combined eye-head movements have large enough amplitudes to create accurate gaze saccades; however, because of increased neck stiffness and viscosity, the head movements produced are smaller, slower, longer, and more delayed than they should be. VOR suppression is disproportionate to the size of the actual gaze saccades because sensory feedback signals from neck proprioceptors are non-veridical, likely due to prolonged coactivation of cervical muscles. The outcome of these changes in eye-head kinematics is head-on-trunk stability at the expense of gaze accuracy. In the absence of vestibular loss, the practical consequences may be dizziness (cervical vertigo) in the short term and imbalance and falls in the long term.

Action and perception are temporally coupled by a common mechanism that leads to a timing misperception.

We move our eyes to explore the world, but visual areas determining where to look next (action) are different from those determining what we are seeing (perception). Whether, or how, action and perception are temporally coordinated is not known. The preparation time course of an action (e.g., a saccade) has been widely studied with the gap/overlap paradigm with temporal asynchronies (TA) between peripheral target onset and fixation point offset (gap, synchronous, or overlap). However, whether the subjects perceive the gap or overlap, and when they perceive it, has not been studied. We adapted the gap/overlap paradigm to study the temporal coupling of action and perception. Human subjects made saccades to targets with different TAs with respect to fixation point offset and reported whether they perceived the stimuli as separated by a gap or overlapped in time. Both saccadic and perceptual report reaction times changed in the same way as a function of TA. The TA dependencies of the time change for action and perception were very similar, suggesting a common neural substrate. Unexpectedly, in the perceptual task, subjects misperceived lights overlapping by less than ∼100 ms as separated in time (overlap seen as gap). We present an attention-perception model with a map of prominence in the superior colliculus that modulates the stimulus signal's effectiveness in the action and perception pathways. This common source of modulation determines how competition between stimuli is resolved, causes the TA dependence of action and perception to be the same, and causes the misperception.

Vestibulo-ocular reflex suppression during head-fixed saccades reveals gaze feedback control.

Previous experiments have shown that the vestibulo-ocular reflex (VOR) is partially suppressed during large head-free gaze (gaze = eye-in-head + head-in-space) shifts when both the eyes and head are moving actively, on a fixed body, or when the eyes are moving actively and the head passively on a fixed body. We tested, in human subjects, the hypothesis that the VOR is also suppressed during gaze saccades made with en bloc, head and body together, rotations. Subjects made saccades by following a target light. During some trials, the chair rotated so as to move the entire body passively before, during, or after a saccade. The modulation of the VOR was a function of both saccade amplitude and the time of the head perturbation relative to saccade onset. Despite the perturbation, gaze remained accurate. Thus, VOR modulation is similar when gaze changes are programmed for the eyes alone or for the eyes and head moving together. We propose that the brain always programs a change in gaze using feedback based on gaze and head signals, rather than on separate eye and head trajectories.

Saccade detection using a particle filter.

BACKGROUND: When healthy subjects track a moving target, "catch-up" saccades are triggered to compensate for the non-perfect tracking gain. The evaluation of the pursuit and/or saccade kinematics requires that saccade and pursuit components be separated from the eye movement trace. A similar situation occurs when analyzes eye movements of patients that could contain eye drifts between saccades. This task is especially difficult, because the range of saccadic amplitudes goes from microsaccades (less than 1°) to large exploratory saccades (40°). NEW METHOD: In this paper we proposed a new algorithm to detect saccades based on a particle filter. The new method suppresses the baseline velocity component linked to smooth pursuit (or to eye drifts) and thus permits a constant threshold during a trial despite the smooth pursuit behavior. It also accounts for a wide range of saccade amplitudes. RESULTS: The new method is validated with five different paradigms, microsaccades, microsaccades plus saccades with drift, linear target motion, non-linear target motion and free viewing. The sensitivity of the method to signal noise is analyzed. COMPARISON WITH EXISTING METHODS: Traditional saccade detection algorithms using a velocity (or acceleration or jerk) threshold can be inadequate because of the baseline velocity component linked to the smooth pursuit (especially if the target motion is non-linear, i.e. not constant velocity) or to eye drifts between saccades. CONCLUSIONS: The new method detects saccades in challenging situations involving eye movements between saccades (smooth pursuit and/or eye drifts) and unfiltered recordings.

Catch-up saccades in head-unrestrained conditions reveal that saccade amplitude is corrected using an internal model of target movement.

This study analyzes how human participants combine saccadic and pursuit gaze movements when they track an oscillating target moving along a randomly oriented straight line with the head free to move. We found that to track the moving target appropriately, participants triggered more saccades with increasing target oscillation frequency to compensate for imperfect tracking gains. Our sinusoidal paradigm allowed us to show that saccade amplitude was better correlated with internal estimates of position and velocity error at saccade onset than with those parameters 100 ms before saccade onset as head-restrained studies have shown. An analysis of saccadic onset time revealed that most of the saccades were triggered when the target was accelerating. Finally, we found that most saccades were triggered when small position errors were combined with large velocity errors at saccade onset. This could explain why saccade amplitude was better correlated with velocity error than with position error. Therefore, our results indicate that the triggering mechanism of head-unrestrained catch-up saccades combines position and velocity error at saccade onset to program and correct saccade amplitude rather than using sensory information 100 ms before saccade onset.

Hierarchical control of two-dimensional gaze saccades.

Coordinating the movements of different body parts is a challenging process for the central nervous system because of several problems. Four of these main difficulties are: first, moving one part can move others; second, the parts can have different dynamics; third, some parts can have different motor goals; and fourth, some parts may be perturbed by outside forces. Here, we propose a novel approach for the control of linked systems with feedback loops for each part. The proximal parts have separate goals, but critically the most distal part has only the common goal. We apply this new control policy to eye-head coordination in two-dimensions, specifically head-unrestrained gaze saccades. Paradoxically, the hierarchical structure has controllers for the gaze and the head, but not for the eye (the most distal part). Our simulations demonstrate that the proposed control structure reproduces much of the published empirical data about gaze movements, e.g., it compensates for perturbations, accurately reaches goals for gaze and head from arbitrary initial positions, simulates the nine relationships of the head-unrestrained main sequence, and reproduces observations from lesion and single-unit recording experiments. We conclude by showing how our model can be easily extended to control structures with more linked segments, such as the control of coordinated eye on head on trunk movements.

Neuromimetic model of saccades for localizing deficits in an atypical eye-movement pathology.

BACKGROUND: When patients with ocular motor deficits come to the clinic, in numerous situations it is hard to relate their behavior to one or several deficient neural structures. We sought to demonstrate that neuromimetic models of the ocular motor brainstem could be used to test assumptions of the neural deficits linked to a patient's behavior. METHODS: Eye movements of a patient with unexplained neurological pathology were recorded. We analyzed the patient's behavior in terms of a neuromimetic saccadic model of the ocular motor brainstem to formulate a pathophysiological hypothesis. RESULTS: Our patient exhibited unusual ocular motor disorders including increased saccadic peak velocities (up to ≈1000 deg/s), dynamic saccadic overshoot, left-right asymmetrical post-saccadic drift and saccadic oscillations. We show that our model accurately reproduced the observed disorders allowing us to hypothesize that those disorders originated from a deficit in the cerebellum. CONCLUSION: Our study suggests that neuromimetic models could be a good complement to traditional clinical tools. Our behavioral analyses combined with the model simulations localized four different features of abnormal eye movements to cerebellar dysfunction. Importantly, this assumption is consistent with clinical symptoms.

pyElectrode: an open-source tool using structural MRI for electrode positioning and neuron mapping.

Neurophysiologists want to place the tip of an electrode in a specific area of the brain. The coordinates of this area can be obtained from standard stereotaxic atlases. However, individual brains may not align with the atlas exactly. Additionally, for chronic recordings, electrodes are placed through a chamber attached to the animal's skull. Thus, the user wants to know where the area of interest is in chamber coordinates, not stereotaxic coordinates. After the chamber has been attached an MRI is often made. This assists in electrode placement, as the location of a target relative to the chamber can be determined based on the atlas. However, doing this in practice requires rough estimation or cumbersome calculations. pyElectrode provides a graphical display and performs calculations necessary to convert between stereotaxic and chamber coordinates, thus facilitating MR-based targeting from an implanted chamber. It also allows the experimenter to visualize recording or stimulation sites during experiments. Finally, it can display and output those sites on an MRI slice background in a format suitable for publication.

Target motion direction influence on tracking performance and head tracking strategies in head-unrestrained conditions.

We examined subjects' behavior when they tracked periodic oscillating targets moving along a randomly oriented ramp with the head free to move. This study focuses on the effect of target motion direction on pursuit performance and on head tracking strategies used by human subjects to coordinate eye and head movements. Our analyses revealed that the gaze tracking gain was modulated by both target oscillation frequency and target motion direction. We found that pursuit gain was modulated by the target motion direction: vertical pursuit being less accurate than horizontal pursuit. While gaze tracking was sensitive to target frequency and orientation, head behavior was less modulated by a change of target frequency than by a change of target motion direction. Additionally, subjects had two main strategies for moving their head: They oriented their head to favor rotations around either the head dorsoventral (target motion directions <20 deg) or mediolateral axis (target motion directions >70 deg). In between, the subjects did not choose a consistent rotation axis for identical target motion directions.