Parkinson's disease (PD) is a progressive, neurological movement disorder. The stability of eye movements in PD is not well understood but many patients report difficulty doing tasks that require stabilized fixation and gaze. The ability to stabilize an image on the retina is critical is acquiring visual information. The purpose of this study was to compare the stability of fixational eye movements of PD patients to those of age-matched controls. Eye movements during simple fixation tasks were recorded from 66 subjects (ages 52 to 84), and 36 age-matched controls (ages 58-85). The absolute velocity of the fixational eye movements were recorded and correlated to a clinical measure of disease progression as measured by the Unified Parkinson's Disease Rating Scale (UPDRS). Unstable, non-rhythmic eye movements were seen in the PD patients. There were significant differences in the absolute velocity and standard deviation between the control group and the PD group in both the horizontal and vertical directions. The correlation of the absolute velocity to the UPDRS was not significant. Parkinson's disease does appear to affect the stability of eye movements. The instabilities in the eye movements appear to precede body tremor. This could lead to an early method for diagnosis and analysis of the disease.

Neurologinių sutrikimų nustatymui dažnai naudojamas sekamųjų akių judesių tyrimas. Tačiau mokslinėje literatūroje nėra detaliai išnagrinėtas vienas sekamųjų akių judesių parametras – pasivejančių sakadų tarpsakadinis laiko intervalas. Taip pat, pasivejančių sakadų parametrų priklausomybė nuo sekamo objekto trajektorijos ir greičio nėra aiški. Šio darbo tikslas - ištirti sekimo paklaidos, sakadų dažnio aplink okliuzijas ir tarpsakadinių laiko intervalų priklausomybę nuo sekamo objekto trajektorijos tipo ir jo judėjimo greičio. / Human oculomotor system analysis is often used to diagnose neurological disorders by studying tracking eye movements of the patient. However, one of the parameters of tracking eye movements is not thoroughly investigated – the intersaccadic interval of catch up saccades. Also, dependencies of parameters of catch-up saccades on different target trajectories and velocities are not clear. The aim of this paper is to study the dependency of tracking error, frequency distribution around occlusions and intersaccadic interval of catch-up saccades on target trajectory and velocity.

Les changements pubertaires peuvent être à l'origine de multiples expériences socio-émotionnelles positives et/ou négatives que les adolescents doiven gérer. Le processus de la régulation émotionnelle (RE) va être grandement sollicité au cours de cette période. La littérature montre que la RE est une fonction psychobiologique dont le développement peut être impacté par divers facteurs environnementaux de l'enfance. Parmi ces facteurs, l'expérienc de l'attachement avec la figure d'attachement y joue un rôle primordial. Cependant, la question cruciale concernant l'impact de l'attachement sur les mécanismes comportementaux et neurophysiologiques des stratégies de RE à l'adolescence reste sous-estimée et les publications à ce sujet sont encore rares. Dans ce contexte, notre étude vise à détem1iner les paramètres oculomoteurs et neurophysiologiques pour les utiliser comme marqueurs potentiel des stratégies de régulation des émotions en fonction du style d'attachement chez les adolescents. Toutefois, la RE est difficilement évaluable avec des outils ne sollicitant que les processus cognitifs conscients des adolescents. À ce titre, il nous a paru nécessaire d'utiliser un dispositif d'eye-tracking synchronisé avec un système de mesure physiologique permet de déterminer les paran1ètres oculomoteurs et neurophysiologiques lors d'exploration des ces images. Cette étude soutient l'hypothèse que l'attachement module des paramètres oculomoteurs et neurophysiologiques des stratégies de la RE Ces résultats pourraient inciter à une nouvelle ligne de recherche afin de proposer une solution thérapeutique dans le contexte de la dysrégulation émotionnelle. / Adolescence is a time of increasing vulnerability to intemalizing and extemalizing psychopathologies associated with poor emotion regulation, including depression, anxiety and antisocial behavior. Emotion regulation is the ability to recrui processes to influence emotion generation. It is therefore important to understand how emotion regulation develops at thi time and how this relates to ongoing development in adolescence. In recent years there has been increasing interest in how attachment styles modulate emotion regulation strategies. However, few researches have addressed this question directly in adolescence. The crucial question conceming the behavioral and neurophysiological mechanisms ofregulatior strategies emotions in adolescence remains underestimated. Employing a specific, an ecologically valid paradigm, the current study determines the oculomotor and neurophysiologie patterns as a potential marker of emotion regulation strategies i.e., comfort and proximity seeking as a function ofattachment style in healthy adolescents. The Attachment Scale Interview was used to detennine attachment style (i.e., secure, fearful, enmeshed and avoidant) in eighty-one healthy adolescents. A synchronized eye-tracking and physiologie measurement device was used to determine gaze and neurophysiologie parameters, respectively, on attachment-related pictures issue from The BASP-Ado. Our results show the existence of different profiles of emotional regulation in adolescence. These results could encourage a new line of research in order to offer a therapeutic solution in the context of emotional dysregulation.

No description available.

L’attention et l’Adaptation Saccadique (AS) sont des composants essentiels de la perception visuelle, le premier renforce le traitement sensoriel des items sélectionnés, le second maintient la précision des mouvements des yeux vers ceux-ci. Ils partagent aussi une dichotomie : les saccades volontaires et l’orientation endogène de l’attention suivent nos buts internes tandis que les saccades réactives et l’orientation exogène répondent aux changements soudains dans l’espace visuel. Leurs substrats neuronaux se superposent en partie. Enfin, chacun impacte l’autre au niveau comportemental. Ce travail de doctorat étudie l’hypothèse d’un couplage fonctionnel entre attention et AS.Toutes nos études chez l’humain sain reposent sur la mesure des performances attentionnelles avant et après l’exposition à l’AS (ou contrôle). Dans la première nous avons exploré les bases neurophysiologiques du couplage réactif/exogène en magnétoencéphalographie. Dans la suivante nous avons comparé l’orientation exogène mesurée par un paradigme de Posner avant et après AS réactive. La dernière, basée sur le même modèle, explorait la modalité volontaire/endogène. Nos résultats montrent que l’AS augmente l’activité oscillatoire gamma et renforce l’orientation de l’attention spatiale. Nous proposons que le couplage repose sur la co-activation de populations neuronales par la plasticité oculomotrice et l’attention au niveau du Cortex Pariétal Postérieur (CPP). Cette activation émerge initialement d’un double effet du cervelet qui inhibe le CPP gauche et active le CPP droit. Cet effet augmente la dominance hémisphérique droite et le biais attentionnel vers la gauche. Notre travail ouvre des perspectives de rééducation des déficits visuo-attentionels / Attention and Saccadic Adaptation (SA) are critical components of visual perception, the former enhancing sensory processing of selected objects, the latter maintaining the eye movements accuracy towards them. Also, a similar dichotomy could be applied to both: voluntary saccades and endogenous attentional shifts follow internal goals while reactive saccades and exogenous shifts are elicited by sudden changes in the environment. Further, their neural substrates partially overlap and they impact each other behaviorally. This PhD work investigates the hypothesis of a functional coupling linking attention and SA in healthy humans. Our experimental contributions all rely on the measurement of attentional performances before and after an exposure to SA (or control). In the first study, we recorded brain magnetic fields to investigate neurophysiological bases of the reactive/exogenous coupling. In the second study, we compared exogenous orienting measured in a Posner-like paradigm before and after reactive SA. Finally, using the same design, the third experiment investigated the voluntary/endogenous modality. We found that SA increased gamma band activity and boosted the orienting of spatial attention. We thus propose that this functional coupling relies on neuronal populations co-activated by both oculomotor plasticity and attention in the Posterior Parietal Cortex (PPC). The initial activation would emerge from a dual effect of the cerebellum inhibiting the left PPC and activating the right PPC. This effect would increase the right hemispheric dominance and the leftward attentional bias. This work opens new perspectives for the rehabilitation of visuoattentional deficits

In binocular rivalry, paradigms have been proposed for unobtrusive moment-by-moment readout of observers' perceptual experience (“no-report paradigms”). Here, we take a first step to extend this concept to auditory multistability. Observers continuously reported which of two concurrent tone sequences they perceived in the foreground: high-pitch (1008 Hz) or low-pitch (400 Hz) tones. Interstimulus intervals were either fixed per sequence (Experiments 1 and 2) or random with tones alternating (Experiment 3). A horizontally drifting grating was presented to each eye; to induce binocular rivalry, gratings had distinct colors and motion directions. To associate each grating with one tone sequence, a pattern on the grating jumped vertically whenever the respective tone occurred. We found that the direction of the optokinetic nystagmus (OKN)—induced by the visually dominant grating—could be used to decode the tone (high/low) that was perceived in the foreground well above chance. This OKN-based readout improved after observers had gained experience with the auditory task (Experiments 1 and 2) and for simpler auditory tasks (Experiment 3). We found no evidence that the visual stimulus affected auditory multistability. Although decoding performance is still far from perfect, our paradigm may eventually provide a continuous estimate of the currently dominant percept in auditory multistability.

L’étude des nystagmus du nourrisson est difficile pour des raisons méthodologiques. La plupart des études sont donc réalisées chez des adultes et a posteriori. Ces études chez l’adulte ont permis la révision des classifications des nystagmus infantiles, avec la consolidation des concepts de syndrome du nystagmus précoce et de nystagmus de type latent. La séméiologie et l’étiopathogénie des nystagmus du nourrisson – notamment des formes comportant un élément vertical et des formes transitoires – reste donc à étudier. Dans ce but : 1. Nous avons développé de nouvelles techniques d’enregistrement des mouvements oculaires chez les nourrissons, utilisables dans le cadre d’une consultation. Elles incluent de nouveaux stimuli, un appareil d’enregistrement des mouvements oculaires spécialement conçu pour le nourrisson et de nouvelles méthodes d’analyse statistique du signal. Nous avons vérifié la faisabilité de ces enregistrements chez 28 nourrissons atteints de nystagmus. 2. Nous avons étudié systématiquement 32 cas de nystagmus de type spasmus nutans, classiquement considéré comme une entité bénigne idiopathique, avec un examen clinique complet, une imagerie cérébrale, une électrophysiologie visuelle et des enregistrements oculo-moteurs. Dans 53,1% des cas, le spasmus nutans était le symptôme d’une autre maladie : neurologique (34,3%), notamment des gliomes du chiasma (21,9%), ou rétinienne (12,5%). Une atteinte des voies visuelles antérieures est probablement en cause dans la physiopathologie des spasmus nutans. 3. Huit cas de nystagmus ayant conduit au diagnostic de gliome des voies optiques (GVO) ont été également enregistrés et étudiés. L’âge d’apparition du nystagmus allait de 2,5 à 10 mois. Le GVO était toujours chiasmatique et constituait une sous-population spécifique. Le nystagmus était toujours de type spasmus nutans. Les enregistrements oculo-moteurs montraient : une fréquence entre 2,7 et 5 Hz, une morphologie sinusoïdale du nystagmus, une dissociation et une dysconjugaison particulière, avec une opposition de phase (180°) entre les oscillations des deux yeux dans le plan horizontal mais une correspondance de phase dans le plan vertical, à l’origine d’un mouvement semblable à un mouvement de convection. Rarement et brièvement, le rapport de phase changeait. Ces caractéristiques orientent vers des oscillations dans le système des vergences, possiblement la conséquence d’une atteinte des afférences sensorielles des centres du contrôle vergentiel dans le tronc cérébral, secondaire au GVO et survenant pendant la période sensible du développement visuel. 4. Cinq cas de nystagmus upbeat chez des nourrissons avec des rétines et une imagerie cérébrale normale ont été étudiés. Le nystagmus était observé en décubitus et électivement déclenché par des rotations de la tête en position allongée. Dans tous les cas, une résolution spontanée était observée après quelques mois d’évolution. Les caractéristiques de ce type de nystagmus suggèrent une participation du système otolithique, suivie d’une recalibration secondaire des circuits vestibulo-oculaires. En conclusion, le développement de techniques d’enregistrement des mouvements oculaires adaptées aux nourrissons aide à la compréhension de l’étiopathogénie de variétés mal décrites de nystagmus, notamment dans les cas comportant un élément vertical et dans les cas transitoires. Les processus de maturation des voies visuelles antérieures et des centres de contrôle de l’oculomotricité semblent jouer un rôle central dans les mécanismes de ces nystagmus. / Studying infantile nystagmus during infancy is difficult for methodological reasons. Most such studies have been performed in adults and a posteriori. These studies in adults allowed for an improvement in the existing classifications, with now robust knowledge about the two most frequent varieties of infantile nystagmus: infantile nystagmus syndrome and fusion maldevelopment nystagmus syndrome. The characteristics and pathophysiology of nystagmus in infants–notably varieties of nystagmus with a vertical component and transitory nystagmus– need further study. For this reason: 1. We developed new techniques for the recording of eye movements in infants in the setting of a clinic. They include new stimuli, the use of specially-designed infrared photo-oculography eyetrackers and new statistical analysis paradigms. We assessed these techniques in a population of 28 infants with a nystagmus. 2. We systematically studied 32 cases of spasmus nutans, classically considered an idiopathic entity, with comprehensive clinical examination, brain imaging, electrophysiology, nystagmus recording. In 53.1% of cases, it led to the diagnosis of another condition: a neurological disease (34.3%), including cases of chiasmal gliomas (21.9%), or a retinal dysfunction (12.5%). Anterior visual pathway dysfunction is likely involved in the pathophysiology of spasmus nutans. 3. Eight cases of nystagmus having led to a diagnosis of optic pathway glioma (OPG) were also recorded and studied. Age at nystagmus onset was 2.5-10 months. The associated OPG always involved the chiasm, and represent a specific subpopulation of OPG. Clinically, the nystagmus was always classified as spasmus nutans type. Oculographic recordings showed frequencies of 2.7-5 Hz, sinusoidal waveforms, dissociation and a special type of disconjugacy, with a 180° horizontal phase shift and no vertical phase shift, exhibiting a “convection-like” movement pattern. Rarely and for short periods of time, the phase shift could change. These characteristics point towards oscillations in the vergence system, which could possibly result from the specific disruption of the vergence centres afferences in the brainstem, induced by the OPG during the sensitive period of visual development. 4. Five cases of upbeat nystagmus in infants with normal retinas and normal brain imaging were studied. The nystagmus mostly occurred in supine position and could be triggered by head rotations in the supine position. All resolved spontaneously. The characteristics of this nystagmus suggest an involvement of the otolithic system, with a secondary recalibration of the vestibulo-ocular pathways. In conclusion, the development of infant-friendly devices for eye-movements recording helps providing new insights on the pathophysiology of poorly described varieties of nystagmus, including nystagmus with a vertical component and transitory nystagmus. The maturation process of both the anterior visual pathways and the oculomotor pathways appears to be central in the mechanisms of these nystagmus.

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

In binocular rivalry, paradigms have been proposed for unobtrusive moment-by-moment readout of observers' perceptual experience (“no-report paradigms”). Here, we take a first step to extend this concept to auditory multistability. Observers continuously reported which of two concurrent tone sequences they perceived in the foreground: high-pitch (1008 Hz) or low-pitch (400 Hz) tones. Interstimulus intervals were either fixed per sequence (Experiments 1 and 2) or random with tones alternating (Experiment 3). A horizontally drifting grating was presented to each eye; to induce binocular rivalry, gratings had distinct colors and motion directions. To associate each grating with one tone sequence, a pattern on the grating jumped vertically whenever the respective tone occurred. We found that the direction of the optokinetic nystagmus (OKN)—induced by the visually dominant grating—could be used to decode the tone (high/low) that was perceived in the foreground well above chance. This OKN-based readout improved after observers had gained experience with the auditory task (Experiments 1 and 2) and for simpler auditory tasks (Experiment 3). We found no evidence that the visual stimulus affected auditory multistability. Although decoding performance is still far from perfect, our paradigm may eventually provide a continuous estimate of the currently dominant percept in auditory multistability.

Made available in DSpace on 2014-12-17T14:56:07Z (GMT). No. of bitstreams: 1 JesseHNB_DISSERT.pdf: 2206144 bytes, checksum: 191ca3ce00f97e4019b5bdb2bc9ab914 (MD5) Previous issue date: 2012-10-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The vision is one of the five senses of the human body and, in children is responsible for up to 80% of the perception of world around. Studies show that 50% of children with multiple disabilities have some visual impairment, and 4% of all children are diagnosed with strabismus. The strabismus is an eye disability associated with handling capacity of the eye, defined as any deviation from perfect ocular alignment. Besides of aesthetic aspect, the child may report blurred or double vision . Ophthalmological cases not diagnosed correctly are reasons for many school abandonments. The Ministry of Education of Brazil points to the visually impaired as a challenge to the educators of children, particularly in literacy process. The traditional eye examination for diagnosis of strabismus can be accomplished by inducing the eye movements through the doctor s instructions to the patient. This procedure can be played through the computer aided analysis of images captured on video. This paper presents a proposal for distributed system to assist health professionals in remote diagnosis of visual impairment associated with motor abilities of the eye, such as strabismus. It is hoped through this proposal to contribute improving the rates of school learning for children, allowing better diagnosis and, consequently, the student accompaniment / A vis?o ? um dos cinco sentidos do corpo humano e, em crian?as, ? respons?vel por at? 80% da percep??o do mundo ao redor. Estudos revelam que 50% das crian?as com m?ltiplas defici?ncias possuem alguma defici?ncia visual, sendo que 4% de todas as crian?as s?o diagnosticadas com estrabismo. O estrabismo ? uma defici?ncia ocular associada ? capacidade de movimenta??o dos olhos, caracterizada por qualquer desvio no alinhamento ocular perfeito. Al?m do aspecto est?tico, a crian?a pode relatar vista emba?ada ou dupla . Problemas oftalmol?gicos n?o diagnosticados corretamente s?o motivos de muitos abandonos da escola. O Minist?rio da Educa??o do Brasil aponta as defici?ncias visuais como um grande desafio aos educadores de crian?as, principalmente no processo de alfabetiza??o. O exame oftalmol?gico tradicional para diagn?stico do estrabismo pode ser realizado induzindo os movimentos oculares atrav?s de instru??es do m?dico ao paciente. Esse procedimento pode ser reproduzido com aux?lio computacional atrav?s da an?lise de imagens capturadas em v?deo. Este trabalho apresenta uma proposta de sistema de teleoftalmologia para auxiliar profissionais da sa?de no diagn?stico a dist?ncia de defici?ncias visuais associadas ? capacidade motora dos olhos, como o estrabismo. Espera-se atrav?s deste trabalho contribuir diretamente para a melhoria dos ?ndices do aprendizado escolar infantil, permitindo melhores condi??es de diagn?stico e, consequentemente, acompanhamento do aluno