Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Eye-Movement-Based Assessment of the Perceptual Consequences of Glaucomatous and Neuro-Ophthalmological Visual Field Defects

Purpose: Assessing the presence of visual field defects (VFD) through procedures such as perimetry is an essential aspect of the management and diagnosis of ocular disorders. However, even the latest perimetric methods have shortcomings & mdash;a high cognitive demand and requiring prolonged stable fixation and feedback through a button response. Consequently, an approach using eye movements (EM)& mdash;as a natural response & mdash;has been proposed as an alternate way to evaluate the presence of VFD. This approach has given good results for computer-simulated VFD. However, its use in patients is not well documented yet. Here we use this new approach to quantify the spatiotemporal properties (STP) of EM of various patients suffering from glaucoma and neuro-ophthalmological VFD and controls. Methods: In total, 15 glaucoma patients, 37 patients with a neuro-ophthalmological disorder, and 21 controls performed a visual tracking task while their EM were being recorded. Subsequently, the STP of EM were quantified using a cross-correlogram analysis. Decision trees were used to identify the relevant STP and classify the populations. Results: We achieved a classification accuracy of 94.5% (TPR/sensitivity = 96%, TNR/specificity = 90%) between patients and controls. Individually, the algorithm achieved an accuracy of 86.3% (TPR for neuro-ophthalmology [97%], glaucoma [60%], and controls [86%]). The STP of EM were highly similar across two different control cohorts. Conclusions: In an ocular tracking task, patients with VFD due to different underlying pathology make EM with distinctive STP. These properties are interpretable based on different clinical characteristics of patients and can be used for patient classification. Translational Relevance: Our EM-based screening tool may complement existing perimetric techniques in clinical practice. Superscript/Subscript Available ABSTRACT Purpose: Assessing the presence of visual field defects (VFD) through procedures such as perimetry is an essential aspect of the management and diagnosis of ocular disorders. However, even the latest perimetric methods have shortcomings?a high cognitive demand and requiring prolonged stable fixation and feedback through a button response. Consequently, an approach using eye movements (EM)?as a natural response?has been proposed as an alternate way to evaluate the presence of VFD. This approach has given good results for computer-simulated VFD. However, its use in patients is not well documented yet. Here we use this new approach to quantify the spatiotemporal properties (STP) of EM of various patients suffering from glaucoma and neuro-ophthalmological VFD and controls. Methods: In total, 15 glaucoma patients, 37 patients with a neuro-ophthalmological disorder, and 21 controls performed a visual tracking task while their EM were being recorded. Subsequently, the STP of EM were quantified using a cross-correlogram analysis. Decision trees were used to identify the relevant STP and classify the populations. Results: We achieved a classification accuracy of 94.5% (TPR/sensitivity = 96%, TNR/specificity = 90%) between patients and controls. Individually, the algorithm achieved an accuracy of 86.3% (TPR for neuro-ophthalmology [97%], glaucoma [60%], and controls [86%]). The STP of EM were highly similar across two different control cohorts

Eye Movement Evaluation in Multiple Sclerosis and Parkinson's Disease Using a Standardized Oculomotor and Neuro-Ophthalmic Disorder Assessment (SONDA)

Evaluating the state of the oculomotor system of a patient is one of the fundamental tests done in neuro-ophthalmology. However, up to date, very few quantitative standardized tests of eye movements' quality exist, limiting this assessment to confrontational tests reliant on subjective interpretation. Furthermore, quantitative tests relying on eye movement properties, such as pursuit gain and saccade dynamics are often insufficient to capture the complexity of the underlying disorders and are often (too) long and tiring. In this study, we present SONDA (Standardized Oculomotor and Neurological Disorder Assessment): this test is based on analyzing eye tracking recorded during a short and intuitive continuous tracking task. We tested patients affected by Multiple Sclerosis (MS) and Parkinson's Disease (PD) and find that: (1) the saccadic dynamics of the main sequence alone are not sufficient to separate patients from healthy controls; (2) the combination of spatio-temporal and statistical properties of saccades and saccadic dynamics enables an identification of oculomotor abnormalities in both MS and PD patients. We conclude that SONDA constitutes a powerful screening tool that allows an in-depth evaluation of (deviant) oculomotor behavior in a few minutes of non-invasive testing

Using eye movements to detect visual field loss: a pragmatic assessment using simulated scotoma.

Glaucoma is a leading cause of irreversible sight-loss and has been shown to affect natural eye-movements. These changes may provide a cheap and easy-to-obtain biomarker for improving disease detection. Here, we investigated whether these changes are large enough to be clinically useful. We used a gaze-contingent simulated visual field (VF) loss paradigm, in which participants experienced a variable magnitude of simulated VF loss based on longitudinal data from a real glaucoma patient (thereby controlling for other variables, such as age and general health). Fifty-five young participants with healthy vision were asked to view two short videos and three pictures, either with: (1) no VF loss, (2) moderate VF loss, or (3) advanced VF loss. Eye-movements were recorded using a remote eye tracker. Key eye-movement parameters were computed, including saccade amplitude, the spread of saccade endpoints (bivariate contour ellipse area), location of saccade landing positions, and similarity of fixations locations among participants (quantified using kernel density estimation). The simulated VF loss caused some statistically significant effects in the eye movement parameters. Yet, these effects were not capable of consistently identifying simulated VF loss, despite it being of a magnitude likely easily detectable by standard automated perimetry

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approach:Functional Biomarkers to Assess Visual System Integrity

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approac

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approach:Functional Biomarkers to Assess Visual System Integrity

Functional Biomarkers to Assess Visual System Integrity: An eye tracking based approac

Encoding of saccadic scene changes in the mouse retina

The task of the visual system is to extract behaviourally relevant information from the visual scene. A common strategy for most animals ranging from insects to humans is to constantly reposition gaze by making saccades within the scene. This ‘fixate and saccade’ strategy seems to pose a challenge, as it introduces a highly blurred image on the retina during a saccade, but at the same time acquires a ‘snapshot’ of the world during every fixation. The visual signals on the retina are thus segmented into brief image fixations separated by global motion. What is the response of a ganglion cell to ‘motion blur’ caused by a saccade, and how does it influence the response to subsequent fixations? Also, how does the global motion signal influence the response dynamics of a ganglion cell? In this thesis, we addressed these questions by two complementary approaches. First, we analysed the retinal ganglion cell responses to simulated saccades. We analysed two important aspects of the response - 1) response during a saccade-like motion, 2) response to fixation images. For about half of the recorded cells, we found strong spiking activity during the saccade. This supports the idea that the retina actively encodes the saccade and may signal the abrupt scene change to downstream brain areas. Furthermore, we characterized the responses to the newly fixated image. While there appears to be only little influence of the preceding motion signal itself on these responses, the responses depended strongly on the image content during the fixation period prior to the saccade. Thus, saccadic vision may provide ‘temporal context’ to each fixation, and ganglion cells encode image transitions rather than currently fixated images. Based on this perspective, we classified retinal ganglion cells into five response types, suggesting that the retina encodes at least five parallel channels of information under saccadic visual stimulation. The five response types identified in this study are as follows: 1) Classical Encoders - Response only to preferred stimuli; 2) Offset Detectors - Response only to the saccade; 3) Indifferent Encoders - Response to all fixated images; 4) Change Detectors - Response only when the new image after the saccade differs from the previous image; 5) Similarity Detectors - Response only when the new image after the saccade is similar to the previous image. Second, we analysed the influence of global motion signals on the response of a retinal ganglion cell to the stimulus in its receptive field. The stimulus beyond the receptive field is designated as remote stimulus. We chose simple stimulus that represent various configurations used in earlier studies, thus allowing us to compare our results. We show that the remote stimulus both enhances and suppresses the mean firing rate, but only suppresses the evoked activity. Furthermore, we show that the remote stimulus decreases the contrast sensitivity and modifies the response gain. Thus, the ganglion cells encode the stimulus in relation to the whole scene, rather than purely respond to the stimulus in the receptive field. Our results suggest that the global motion signals provide ‘spatial context’ to the response of the stimulus within the receptive field

Visual and Chemosensory Pathways Associated With Male Courtship Decisions in Drosophila melanogaster

Successful mating in diverse animal species often depends on ritualistic sequences of spatially and temporally coordinated behavioral elements. Yet, the sensory cues and neural circuits that mediate optimal mating display patterns are largely unknown. The courtship ritual in Drosophila melanogaster consists of a well-studied sequence of behavioral elements — including orienting, chasing, tapping, singing, and licking — that are known to depend on several sensory modalities, including both vision and chemosensation. However, the specific sensory inputs utilized by males to direct the spatial and temporal transitions between different elements of the courtship ritual are not well understood. In this thesis, I therefore first develop a new computational tool to quantitatively characterize male courtship behaviors with a high spatial and temporal resolution. Subsequently, I use this tool, in conjunction with genetic and microscopy approaches to map the visual and chemosensory neural pathways that drive some of the patterned behavioral elements of the male courtship ritual. I demonstrate that whereas visual circuits are important for mediating both spatial and temporal components of male mating behaviors, chemosensory circuits are mostly required for enhancing the duration and intensity of courtship bouts. Further, I identify a male-specific axonal architecture present in subpopulations of foreleg chemosensory neurons which is important for helping to sustain mating behaviors. This thesis examines the inputs, processing centers, and neural architectures required for the proper organization of innate mating behaviors and should provide insight into understanding how animals transform sensory stimuli into complex behavioral outputs, which is a major goal in modern neuroscience