Clinicians are becoming increasingly aware of the effect of various pathologies on the characteristics of saccadic eye movements. As such, an efficient and non-invasive means of measuring eye-movement in a clinical environment is of interest to many. The aim of this thesis is to investigate the clinical application of a non-invasive eye movement recording technique as a part of a clinical examination. Eye movements were measured using an IRIS 6500 infrared limbal eye tracker, which we customized for the direct recording of oblique eye movements as well as horizontal and vertical. Firstly, the eye-tracker itself was assessed. Visually normal observers made saccadic eye movements to a 10' stimulus in eight directions of gaze. Primary (ANOVA) and secondary analyses (mean error less than 5%) resulted in acceptance that averaging four measurements would give a representative measurement of saccadic latency, peak velocity, amplitude and duration. Test-retest results indicated that this technique gives statistically (± 1.96*STDEVDifference) repeatable responses. Several factors that could potentially influence clinically based measures of eye-movements were examined. These included, the effect of ageing, viewing distances, dioptric blur and cataract. The results showed that saccadic latency and duration are significantly (p < 0.05) longer in older (60-89 years) observers compared to younger (20-39 years). Peak velocity and amplitude were not significantly affected by the age of the observer. All saccadic parameters (SP) were significantly affected by direction (Chapter 5). The compact nature of this eye movement methodology is obtainable since there is no significant effect on viewing distance (300 cm vs. 49 cm) (Chapter 6). There is also no significant effect of dioptric blur (up to +LOODS) on any of the four SP. In contrast, a higher level of defocus (+3.O ODS) has a larger probability of interfering with the measurements of peak velocity and duration (Chapter 7). Saccadic eye-movements were also recorded whilst normally sighted subjects wore cataract simulation goggles. The results suggested that the presence of dense cataract introduces significant increases in saccadic latencies and durations. No effect was found on the peak velocities and amplitudes. The effect of amblyopia on SP was also investigated in order to examine if this methodology is able to detect normal from abnormal responses (i.e. increased saccadic latencies). This set of data (Chapter9 ) showed that using IRIS 6500, longer than normal latencies may be recorded from the amblyopic eye but no consistent effect was found for the other SP (peak velocity, amplitude, duration). Overall, the results of this thesis demonstrate that the IRIS 6500 eye-tracker has many desirable elements (it is non-invasive; comfortable for the observers and gives repeatable and precise results in an acceptable time) that would potentially make it a useful clinical tool as a part of a routine examination.

La saccade oculaire, i.e. mouvement très rapide des yeux, permet d’amener l’objet d’intérêt sur la fovéa, afin que le système visuel puisse analyser ses propriétés. Malgré l’importance du cortex occipital dans le traitement de l’information visuelle, son rôle dans la génération de saccades est encore peu connu. Pour ce faire, l’hémianopsie latérale homonyme consécutive à une atteinte unilatérale du cortex occipital (i.e. amputation de l’hémichamp visuel controlésionnel) peut être considérée comme modèle d’étude. En effet, malgré la perte de la vision consciente, certains patients sont capables de répondre à un stimulus présenté dans l’hémichamp controlésionnel. Ces capacités préservées, appelées vision aveugle, peuvent être de nature attentionnelle et/ou motrice. Le but de cette thèse est ainsi d’étudier l’implication du cortex occipital dans la génération de saccades. En manipulant les propriétés spatiales et temporelles du point de fixation, de la cible ou d’un distracteur, les paramètres des saccades de ces patients ont été examinés en étudiant différents types de saccades (volontaires et réactives) ainsi que des effets connus pour moduler les paramètres saccadiques (effets d’un distracteur et adaptation saccadique). Parallèlement, les capacités de vision aveugle ont été examinées à partir de différentes tâches perceptives (détection et discrimination), nécessitant une réponse verbale, manuelle (appui-bouton) et/ou oculomotrice (saccade et fixation). Malgré la perte de la conscience visuelle du stimulus présenté dans l’hémichamp controlésionnel, des capacités de vision aveugle sont attestées par la réalisation d’une action oculomotrice sur ce stimulus. La dichotomie observée dans ces capacités en fonction de la nécessité de réaliser une action sur la stimulation visuelle suppose une implication du cortex occipital dans les mécanismes de sélection pour l’action et pour la perception. Par ailleurs, une dissociation est observée dans l’atteinte des paramètres saccadiques. Si l’initiation de la saccade – reflétée par la latence - est altérée dans les deux hémichamps ipsi- et controlésionnel, le calcul de la métrique de la saccade – reflétée par l’amplitude - est spécifiquement altéré dans l’hémichamp controlésionnel. Ainsi, nos résultats sont en faveur d’une implication du cortex occipital dans la génération des saccades oculaires ainsi qu’en faveur d’un modèle fonctionnel de génération de saccades à deux voies de traitement parallèles dédiées respectivement à l’initiation et à la métrique de la saccade. / Saccadic eye movements are rapid and necessary to targeting the interesting object in our visual environment. Despite the crucial role of the occipital cortex in the visual process, its implication in the saccadic generation is poorly studied. To examine this, we can use one pathological model, the homonymous hemianopia (i.e. loss of contralateral visual hemifield to unilateral occipital lesion). Despite the loss of conscious vision, some patients can be able to react at one stimulus presented in the contralesional hemifield. These residual abilities, named blindsight, can be observed in attentional and/or motor tasks. The aim of this thesis is examine the parameters of saccades in hemianopic patients, through the study of saccade types (voluntary and reflexive saccades) and classical effects on the modulation of saccadic parameters (gap effect and distractor effects, by manipulating the spatial and temporal characteristics of the fixation point, the target or a distractor). Furthermore, the residual abilities are investigated by perceptual tasks (detection or discrimination) with different types of response: verbal, manual (key press) and motor (saccade or fixation). Overall, despite the loss of conscious perception of the target presented in the contralesional hemifield, residual abilities are found as showed by the saccadic execution toward the target, with a dichotomy depending on the need to perform an action on the visual stimulation. This suggests that the role of the occipital cortex is not the same in the selection mechanism for the action and the perception. Concerning to saccadic programming, dissociation is found in the saccadic parameters. The saccadic initiation, studied by with the saccade latency, is altered in both ipsi- and contralesional hemifields but the saccade metric, studied by the saccade amplitude, is altered in the contralesional hemifield. This suggests that the occipital cortex is implicated in the saccade generation and that saccade programing involves two pathways for the initiation and the metric of saccades.

Obwohl Blickbewegungen einen elementaren Bestandteil des natürlichen Sehens darstellen, werden hirnelektrische Korrelate der visuellen Verarbeitung im Elektroenzephalogramm (EEG) zumeist während passiver Stimulation des ruhenden Auges erfasst. Ein alternativer methodischer Zugang ist die Kopplung des EEG an Beginn oder Ende natürlich auftretender Augenbewegungen mit Hilfe simultanen, hochauflösenden Eye-Trackings (ET). Die resultierenden sakkaden- bzw. fixationskorrelierten Potentiale (SRPs/FRPs) wurden in zwei Forschungskontexten untersucht und angewendet. Der erste Teil der Arbeit (Publikation 1 & 2) befasst sich mit den elektrophysiologischen Korrelaten von Mikrosakkaden, unwillkürlichen Fixationsaugenbewegungen die auch während traditioneller EEG-Messungen auftreten. Es wird gezeigt, dass Mikrosakkaden trotz ihrer geringen Amplitude eine wesentliche, aber mit herkömmlichen Methoden kaum auszuschließende Quelle muskulärer und kortikaler Aktivität im EEG darstellen (mikrosakkadische SRPs), welche in der Mehrzahl experimenteller Durchgängen aktiv ist, und zur Fehlinterpretation reizgekoppelter Potentiale führen kann. Der zweite Teil der Arbeit demonstriert die Machbarkeit und Nützlichkeit von FRP-Analysen zur Untersuchung hirnelektrischer Prozesse beim Lesen. In Publikation 3 werden Einflüsse verschiedener Messartefakte sowie visuell-evozierter, motorischer und kognitiv modulierter Potentiale auf die FRP-Wellenform beschrieben und Methoden zur Signaloptimierung vorgeschlagen. Wir zeigen, dass sich im natürlichen Satzlesen der klassische N400 Wortvorhersagbarkeitseffekt reproduzieren und in Bezug zu Maßen der Fixationsdauer setzen lässt. In Publikation 4 wurde mittels FRPs das Ausmaß der parafovealen Wortverarbeitung bestimmt. Simultanes ET ist eine sinnvolle Ergänzung zur bestehenden EEG-Methodik, sowohl zur Kontrolle von Mikroaugenbewegungen, als auch zur Erforschung natürlichen Blickbewegungsverhaltens und Integration von Befunden der ET- und EEG-Forschung. / Although natural vision involves an active sampling of the environment with several saccadic eye movements per second, electroencephalographic (EEG) correlates of visual cognition are predominantly recorded under artificial conditions of prolonged fixation. An alternative approach to EEG analysis, explored in the present thesis, is to time-lock the signal not to passive stimulations, but to the on- or offsets of naturally occurring eye movements, yielding saccade- and fixation-related potentials (SRPs/FRPs). Using simultaneous high-resolution eye-tracking (ET), this technique was applied in two contexts. The first part of the thesis (publications 1 & 2) investigated brain-electric correlates of microsaccades, small involuntary eye movements, which occur despite attempted fixation during traditional EEG paradigms. In a series of experiments, we show that SRPs from microsaccades present a significant, but normally hidden source of visuocortical potentials that is active in most trials and can confound the interpretation of stimulus-locked data under specific conditions. The second part of the thesis assessed the feasibility and utility of using FRPs in the study of natural reading. Publication 3 provides a review of artifact sources, low-level factors, and high-level influences determining the FRP waveform in free viewing and proposes methods to optimize signal quality. We then replicate the N400 word predictability effect, a cornerstone of neurolinguistic research, in left-to-right sentence reading and relate N400 amplitude to measures of fixation time. In publication 4, the FRP technique was combined with gaze-contingent display manipulations to investigate the depth of parafoveal preprocessing in fluent reading. Our results show that simultaneous recordings improve the understanding of electrophysiological data recorded during fixation, extend the EEG’s methodological scope to naturalistic viewing scenarios, and help to integrate findings from EEG and ET research.

The electro-oculogram (EOG) is the most widely used technique for recording eye movements in clinical settings. It is inexpensive, practical, and non-invasive. Use of EOG is usually restricted to horizontal recordings as vertical EOG contains eyelid artefact (Oster & Stern, 1980) and blinks. The ability to analyse two dimensional (2D) eye movements may provide additional diagnostic information on pathologies, and further insights into the nature of brain functioning. Simultaneous recording of both horizontal and vertical EOG also introduces other difficulties into calibration of the eye movements, such as different gains in the two signals, and misalignment of electrodes producing crosstalk. These transformations of the signals create problems in relating the two dimensional EOG to actual rotations of the eyes. The application of an artificial neural network (ANN) that could map 2D recordings into 2D eye positions would overcome this problem and improve the utility of EOG. To determine whether ANNs are capable of correctly calibrating the saccadic eye movement data from 2D EOG (i.e. performing the necessary inverse transformation), the ANNs were first tested on data generated from mathematical models of saccadic eye movements. Multi-layer perceptrons (MLPs) with non-linear activation functions and trained with back propagation proved to be capable of calibrating simulated EOG data to a mean accuracy of 0.33° of visual angle (SE = 0.01). Linear perceptrons (LPs) were only nearly half as accurate. For five subjects performing a saccadic eye movement task in the upper right quadrant of the visual field, the mean accuracy provided by the MLPs was 1.07° of visual angle (SE = 0.01) for EOG data, and 0.95° of visual angle (SE = 0.03) for infrared limbus reflection (IRIS®) data. MLPs enabled calibration of 2D saccadic EOG to an accuracy not significantly different to that obtained with the infrared limbus tracking data.

Die Erforschung visueller Aufmerksamkeit beruht auf verdeckter Aufmerksamkeit; das heißt, wenn der Fokus der Aufmerksamkeit trotz strikter Fixation ausgerichtet wird ohne größere Sakkaden auszuführen. EEG-Studien haben das neuronale Netzwerk identifiziert, dass verdeckte Aufmerksamkeit steuert. Diese Studien ignorieren jedoch unwillkürliche kleine Sakkaden während der Fixation - Mikrosakkaden (MS) genannt. Blickbewegungsstudien hingegen belegen einen Zusammenhang zwischen Aufmerksamkeit und diesen MS, beziehen ihre Resultate jedoch nicht auf etablierte EEG-Befunde. Um diese Forschungslücke zu schließen, zielt diese Dissertation darauf, den Zusammenhang zwischen Ereignis-korrelierten Potentialen (EKP) endogener Aufmerksamkeit und MS zu untersuchen. Folglich wurden drei Studien mit gleichzeitiger Erfassung von EEG und Blickbewegungen durchgeführt. In den Studien haben die Probanden ein „Posner Spatial-Cueing-Paradigma“ absolviert mit einem endogenen Hinweisreiz. Wir zeigen deutliche Zusammenhänge zwischen MS und neuronalen Korrelaten visueller Aufmerksamkeit. Erstens, MS und ein posteriores EKP reflektierten die Selektion visueller Reize basierend auf deren Merkmale. Dieses Ergebnis stärkt die Idee eines Netzwerkes, dass relevante Reize unter Distraktoren selektiert und zielgerichtetes Verhalten initiiert. Zweitens, MS erzeugten ein visuelles Potential, das verstärkte Potentialkomponenten für Reize zeigte, die im Aufmerksamkeitsfokus lagen. Dieses MS-evozierte Potential stellte einen zeitlich gut aufgelösten Aufmerksamkeitsindex dar. Drittens, MS erzeugten zudem ein in früheren Studien übersehenes, korneoretinales Artefakt. Dieses Artefakt kontaminierte die Messung eines frontalen EKPs, dass zuvor mit der Kontrolle von Aufmerksamkeit assoziiert war. Zusammenfassend zeigt diese Dissertation, dass die gleichzeitige Erfassung von EEG und Blickbewegungen bedeutsame Einblicke in den Zusammenhang von MS und visueller Aufmerksamkeit erlaubt. / Research on visual attention focusses on covert attention; that is, when attention is directed during fixation periods in the absence of larger saccades. While previous EEG research has provided insights into the neural network that controls covert attention, this field fails to account for the inevitable occurrence of miniature fixational saccades - called microsaccades (MS). In contrast, previous eye-tracking research has established links between MSs and covert attention, but has not directly related their findings to seminal EEG results. This thesis bridges this research gap by investigating the link between event-related potentials (ERPs) of endogenous attention and MSs. To this end, three studies were conducted with concomitant ERP and high-resolution eye-tracking recordings while participants performed a Posner spatial cueing task with an endogenous cue. Crucially, we show that MSs relate to neural correlates of visual attention. First, MS and an early posterior ERP reflected the top-down selection of a visual stimulus based on its features. This finding is consistent with the notion of a neural network that selects relevant stimuli from distracting ones and initiates goal-directed behavior toward selected stimuli. Second, gaze shifts from MSs evoked a visual potential in the EEG that was enhanced for stimuli in the focus of attention; a finding well-known for the visual potential measured after presenting a stimulus. Importantly, these MS-related potentials provided a fine-grained temporal index of the subject’s attentional state. Finally, MSs further evoked a corneoretinal artifact overlooked in previous EEG studies. This artifact contaminated the measurement of a frontal ERP previously associated with preparatory attentional control. In sum, this thesis provides first evidence for the benefits of using concomitant ERP and eye-tracking recordings to examine the link between MSs and visual attention.