Yes / Purpose: To investigate how well visual field sensitivity predicts visual acuity at the same locations in macular disease, and to assess whether such predictions may be useful for selecting an optimum area for fixation training. Methods: Visual field sensitivity and acuity were measured at nine locations in the central 10° in 20 people with AMD and stable foveal fixation. A linear mixed model was constructed to predict acuity from sensitivity, taking into account within-subject effects and eccentricity. Cross validation was used to test the ability to predict acuity from sensitivity in a new patient. Simulations tested whether sensitivity can predict nonfoveal regions with greatest acuity in individual patients. Results: Visual field sensitivity (P < 0.0001), eccentricity (P = 0.007), and random effects of subject on eccentricity (P = 0.043) improved the model. For known subjects, 95% of acuity prediction errors (predicted − measured acuity) fell within −0.21 logMAR to +0.18 logMAR (median +0.00 logMAR). For unknown subjects, cross validation gave 95% of acuity prediction errors within −0.35 logMAR to +0.31 logMAR (median −0.01 logMAR). In simulations, the nonfoveal location with greatest predicted acuity had greatest “true” acuity on median 26% of occasions, and median difference in acuity between the location with greatest predicted acuity and the best possible location was +0.14 logMAR (range +0.04 to +0.17). Conclusions: The relationship between sensitivity and acuity in macular disease is not strongly predictive. The location with greatest sensitivity on microperimetry is unlikely to represent the location with the best visual acuity, even if eccentricity is taken into account. / College of Optometrists Postdoctoral Research Award (JD and ATA; London, UK) and National Institute for Health Research (NIHR) Postdoctoral Fellowship (ATA; London, UK). Presents independent research funded by the NIHR. / Research Development Fund Publication Prize Award winner, August 2018.

Background: To define age-related changes in the visual field by comparing 'standard' central and unique peripheral visual field measurements in healthy volunteers. Methods: In a single center, retrospective, Cross-sectional, observational study, 20 volunteers with no retinal diseases or risk factors, ranging in age between 30 and 94 years (four age groups: 30’s, 50’s, 70’s, 90’s) were measured in one eye (preferentially the right one) using a Humphrey visual field 24–2 and 60–4. Results: While the central visual field remained relatively well preserved during aging showing only a mild reduction in sensitivity, a profound loss of the peripheral visual field was observed beginning in the fifth decade of life and decreasing continuously up to the 90ies. Conclusions: The peripheral visual field declined substantially from the 4th decade onward while the central visual field remained quite stable.

Objetivos: Avaliar a integridade das vias magnocelular (M) e parvocelular (P) atraves da percepcao de contraste e avaliar a sensibilidade no campo visual e respostas no ERG multifocal, em pacientes com esclerose multipla. Métodos e Resultados: Foram avaliados 29 pacientes (20F; 9M; idade media = 35,76 }10,91 anos) com diagnostico de esclerose multipla (15 com historico de neurite optica). Todos os pacientes apresentavam acuidade visual entre 0 e 0,1 logMAR. A percepcao de contraste foi avaliada atraves da funcao de sensibilidade ao contraste (programa PSYCHO; Cambridge Research System), com os limiares medidos em 0.2, 0.5, 1.0, 1.9, 5.3, 9.7 e 19.4 ciclos por grau; e do teste do Pedestal (Pokorny & Smith, 1997). O campo visual foi medido com o Campimetro Automatico de Humphrey, algoritmo SITA, estrategia central 24-2. O ERGmf foi registrado, utilizando o sistema VERIS, com 103 hexagonos. A analise foi baseada nos valores de amplitude e latencia de N1 e P1 das respostas de seis regioes predeterminadas de acordo com o mapa sugerido por Garway-Heath et al (2000), para os kernels de primeira e segunda ordem. Os pacientes foram divididos em 2 grupos: NO (antecedente de neurite optica) e SNO (sem antecedente de neurite optica). Resultados: O grupo NO nao diferiu do grupo SNO em nenhum dos testes, exceto nas medidas de amplitude do kernel de segunda ordem no ERGmf (Tukey HSD Test, PostHoc). Todos os pacientes mostraram uma reducao na percepcao de contraste, quando comparados ao grupo controle. Os resultados diferiram significativamente do grupo controle em todas as frequencias espaciais avaliadas na funcao de sensibilidade ao contraste (p < 0.001; ANOVA), e nos dois paradigmas avaliados pelo teste do Pedestal (p <0.05 ANOVA de medidas repetidas). As respostas do kernel de primeira ordem do ERGmf para ambos os grupos, quando comparados com o grupo controle, nao apresentaram diferenca estatistica significativa para as regioes analisadas (p > 0.05; ANOVA de medidas repetidas). As respostas de amplitude dos pacientes, para o kernel de segunda ordem apresentaram-se diferentes do grupo controle, com significancia estatistica para as areas 2, 3, 4, 5 e 6 (p < 0.05; ANOVA de medidas repetidas). Os resultados do campo visual mostraram reducao de sensibilidade nos pacientes em estudo, comparados ao grupo controle, com diferenca estatisticamente significante para todas as regioes (p <0.05; ANOVA de medidas repetidas). Conclusões: Aumento nos limiares de deteccao de contraste foram encontrados nos pacientes com esclerose multipla, em ambos os testes. O padrao de perda nas varias frequencias espaciais e em ambos os paradigmas analisados no teste do Pedestal, sugere um comprometimento nao seletivo das vias visuais, afetando tanto a via parvo como a magnocelular. As alteracoes nas respostas do ERG multifocal detectadas apenas no kernel de segunda ordem poderiam estar relacionadas a danos retrogrados a camada de fibras nervosas da retina causados pela desmielinizacao. Nao foram encontradas correlacoes com as perdas de sensibilidade no campo visual / Purpose: To assess the integrity of the magnocellular (M) and parvocellular (P) pathways by measuring contrast perception and to evaluate the visual field and multifocal ERG responses in patients with multiple sclerosis. Methods: 29 patients (20F, 9M, mean age = 35.76 } 10.91 years) diagnosed with multiple sclerosis were evaluated (15 with optic neuritis). All patients had visual acuity between 0 and 0.1 logMAR. The contrast perception was assessed by the measurement of contrast sensitivity function (program PSYCHO, Cambridge Research System) using spatial frequencies 0.2, 0.5, 1.0, 1.9, 5.3, 9.7 and 19.4 cycles per degree and the pedestal test (Pokorny & Smith, 1997). The visual field was measured using the central 24-2 SITA algorithm of the Humphrey Field Analyzer. The mfERG was recorded using the Veris system with 103 hexagons in which N1 and P1 amplitude and latency values of six predetermined areas according to the map suggested by Garway-Heath et al (2000) were used (first and second order kernels). Patients were divided into two groups: NO (with optic neuritis) and SNO (without optic neuritis). Results: The NO group did not differ from the SNO in any of the tests except for the second order kernel amplitudes in the mfERG (Tukey HSD posthoc test). All patients showed a reduction in contrast perception compared to the control group. The patients results were significantly different from the control groups at all spatial frequencies tested (p <0.001, ANOVA), and for the two paradigms of the pedestal test (p <0.05, ANOVA). The first order kernel responses in the mfERG showed no significant difference for both patient groups when compared with the control group (p> 0.05, ANOVA). The second order kernel amplitudes were different between patients and controls, with statistical significance for areas 2, 3, 4, 5 and 6 (p <0.05, ANOVA). The visual field results showed sensitivity reductions in the patients compared to controls, which was statistically significant for all regions (p <0.05, ANOVA). Conclusions: Increased thresholds for contrast detection were found in patients with multiple sclerosis in both tests. The pattern of loss in the various spatial frequencies and in both test paradigms of the Pedestal suggests a non-selective impairment of the visual pathways affecting both the parvo and magnocellular pathways. Changes in multifocal ERG responses found only in the second order kernel may be related to retrograde damage of the nerve fiber layer of the retina caused by demyelization. No significant correlation with the visual field losses was found

The left hemisphere (LH) is accepted as the dominant hemisphere for language processing. There is also evidence confirming the language processing abilities of the right hemisphere (RH), particularly its lexical-semantic processing potential (Chiarello, 1988; Joanette, Goulet, & Hannequin, 1990). The capacity of the RH for language processing is significant to the investigation of language processing following LH lesions. However, the precise neurocognitive mechanisms underlying language processing following lesion remain to be fully elucidated. Subsequently, the overall aim for this thesis is to investigate hemispheric contributions to semantic processing following unilateral lesions, and to explore the significance of the contribution made by the RH. In order to achieve this overall aim, the current thesis firstly explores the hemispheric contributions made to lexical-semantic processing for healthy adults, and then shifts focus to explore the changes in hemispheric processing for participants with unilateral lesions (LH and RH). Comparisons of hemispheric activation between these groups will clarify the underlying hemispheric mechanisms that facilitate language processing following unilateral lesion. This thesis includes four complementary investigations of hemispheric contributions to semantic processing. The first study combined divided visual field (DVF) priming with event-related potentials (ERPs), in order to investigate controlled hemispheric semantic priming for young healthy adults. Two experiments were employed for a between subjects comparison of time-course differences (stimulus onset asynchrony, or SOA, varied between experiments) in hemispheric activation of associated and nonassociated category members. Continuous electroencephalograms were recorded throughout the priming task for each participant, and later analysed with reference to relevant ERP components (N400 and Late Positive Complex). Bilateral N400 priming was revealed for associated category members at both the short and long SOA. There was no significant N400 priming for the nonassociated category member condition. The examination of hemispheric priming of associated and nonassociated category member stimuli over the same time-course was continued in the second study for participants with unilateral LH lesions and matched controls. The second investigation aimed to determine the impact of unilateral LH lesions on controlled hemispheric semantic priming, utilising the DVF priming paradigm with participants following unilateral lesions. This study also aimed to explore associations between hemispheric activation during the online priming task and offline comprehension abilities. Differences in priming were observed between the LH lesion group and the control group, with participants in the LH lesion group requiring the association relationship to elicit priming. Priming also varied for participants as a function of their offline comprehension abilities, with RH priming associated with higher offline scores. The third investigation continued the exploration of hemispheric semantic activation following LH lesion, examining the impact of a LH lesion on interhemispheric control mechanisms, and the modification of hemispheric processing capacities with and without dominant hemisphere control. This investigation again utilised DVF priming with associated and nonassociated category member stimuli, in conjunction with the dual task paradigm. The dual task paradigm is designed to overload one hemisphere’s processing resources in order to remove interhemispheric suppression. Findings indicate that following LH lesions, the RH’s contribution is enhanced under conditions that are designed to overload the LH. The final study shifts from the investigation of participants with LH lesions to the impact of a RH lesion. This exploration of controlled hemispheric semantic priming following RH lesion sought to increase our understanding of the underlying mechanisms for semantic processing following unilateral lesion. The RH’s role in lexical-semantic processing has been documented consistently over approximately the last twenty years, however, there remains limited direct investigation of a RH lesion’s impact on contributions to semantic processing. A single case investigation utilised the same experimental procedure as the second study described. Findings suggest a similar activation pattern between the individual with RH lesion and the control participants, with both exhibiting bilateral activation of the associated and nonassociated category member stimuli. However, a subtle difference was found between the activation of the individual with RH lesion and that of the control group, with the individual with a RH lesion showing increased strategic processing difficulties at the longer SOA. Overall, the current thesis demonstrates the importance of the RH for efficient strategic semantic processing for both healthy adults, and people with unilateral lesions. In addition, this thesis concludes that following a LH lesion, the RH contribution to controlled semantic processing may be associated with successful comprehension, and that RH contributions may be improved with the addition of a secondary task designed to overload LH processing. The present thesis provides evidence to support the use of the DVF priming paradigm in the investigation of hemispheric contributions to semantic processing following unilateral lesion. It is anticipated that these findings will improve the current understanding of the underlying hemispheric contributions to lexical-semantics following a unilateral lesion, and will encourage continuing investigation into the RH’s capacity to impact language recovery.

The left hemisphere (LH) is accepted as the dominant hemisphere for language processing. There is also evidence confirming the language processing abilities of the right hemisphere (RH), particularly its lexical-semantic processing potential (Chiarello, 1988; Joanette, Goulet, & Hannequin, 1990). The capacity of the RH for language processing is significant to the investigation of language processing following LH lesions. However, the precise neurocognitive mechanisms underlying language processing following lesion remain to be fully elucidated. Subsequently, the overall aim for this thesis is to investigate hemispheric contributions to semantic processing following unilateral lesions, and to explore the significance of the contribution made by the RH. In order to achieve this overall aim, the current thesis firstly explores the hemispheric contributions made to lexical-semantic processing for healthy adults, and then shifts focus to explore the changes in hemispheric processing for participants with unilateral lesions (LH and RH). Comparisons of hemispheric activation between these groups will clarify the underlying hemispheric mechanisms that facilitate language processing following unilateral lesion. This thesis includes four complementary investigations of hemispheric contributions to semantic processing. The first study combined divided visual field (DVF) priming with event-related potentials (ERPs), in order to investigate controlled hemispheric semantic priming for young healthy adults. Two experiments were employed for a between subjects comparison of time-course differences (stimulus onset asynchrony, or SOA, varied between experiments) in hemispheric activation of associated and nonassociated category members. Continuous electroencephalograms were recorded throughout the priming task for each participant, and later analysed with reference to relevant ERP components (N400 and Late Positive Complex). Bilateral N400 priming was revealed for associated category members at both the short and long SOA. There was no significant N400 priming for the nonassociated category member condition. The examination of hemispheric priming of associated and nonassociated category member stimuli over the same time-course was continued in the second study for participants with unilateral LH lesions and matched controls. The second investigation aimed to determine the impact of unilateral LH lesions on controlled hemispheric semantic priming, utilising the DVF priming paradigm with participants following unilateral lesions. This study also aimed to explore associations between hemispheric activation during the online priming task and offline comprehension abilities. Differences in priming were observed between the LH lesion group and the control group, with participants in the LH lesion group requiring the association relationship to elicit priming. Priming also varied for participants as a function of their offline comprehension abilities, with RH priming associated with higher offline scores. The third investigation continued the exploration of hemispheric semantic activation following LH lesion, examining the impact of a LH lesion on interhemispheric control mechanisms, and the modification of hemispheric processing capacities with and without dominant hemisphere control. This investigation again utilised DVF priming with associated and nonassociated category member stimuli, in conjunction with the dual task paradigm. The dual task paradigm is designed to overload one hemisphere’s processing resources in order to remove interhemispheric suppression. Findings indicate that following LH lesions, the RH’s contribution is enhanced under conditions that are designed to overload the LH. The final study shifts from the investigation of participants with LH lesions to the impact of a RH lesion. This exploration of controlled hemispheric semantic priming following RH lesion sought to increase our understanding of the underlying mechanisms for semantic processing following unilateral lesion. The RH’s role in lexical-semantic processing has been documented consistently over approximately the last twenty years, however, there remains limited direct investigation of a RH lesion’s impact on contributions to semantic processing. A single case investigation utilised the same experimental procedure as the second study described. Findings suggest a similar activation pattern between the individual with RH lesion and the control participants, with both exhibiting bilateral activation of the associated and nonassociated category member stimuli. However, a subtle difference was found between the activation of the individual with RH lesion and that of the control group, with the individual with a RH lesion showing increased strategic processing difficulties at the longer SOA. Overall, the current thesis demonstrates the importance of the RH for efficient strategic semantic processing for both healthy adults, and people with unilateral lesions. In addition, this thesis concludes that following a LH lesion, the RH contribution to controlled semantic processing may be associated with successful comprehension, and that RH contributions may be improved with the addition of a secondary task designed to overload LH processing. The present thesis provides evidence to support the use of the DVF priming paradigm in the investigation of hemispheric contributions to semantic processing following unilateral lesion. It is anticipated that these findings will improve the current understanding of the underlying hemispheric contributions to lexical-semantics following a unilateral lesion, and will encourage continuing investigation into the RH’s capacity to impact language recovery.

The left hemisphere (LH) is accepted as the dominant hemisphere for language processing. There is also evidence confirming the language processing abilities of the right hemisphere (RH), particularly its lexical-semantic processing potential (Chiarello, 1988; Joanette, Goulet, & Hannequin, 1990). The capacity of the RH for language processing is significant to the investigation of language processing following LH lesions. However, the precise neurocognitive mechanisms underlying language processing following lesion remain to be fully elucidated. Subsequently, the overall aim for this thesis is to investigate hemispheric contributions to semantic processing following unilateral lesions, and to explore the significance of the contribution made by the RH. In order to achieve this overall aim, the current thesis firstly explores the hemispheric contributions made to lexical-semantic processing for healthy adults, and then shifts focus to explore the changes in hemispheric processing for participants with unilateral lesions (LH and RH). Comparisons of hemispheric activation between these groups will clarify the underlying hemispheric mechanisms that facilitate language processing following unilateral lesion. This thesis includes four complementary investigations of hemispheric contributions to semantic processing. The first study combined divided visual field (DVF) priming with event-related potentials (ERPs), in order to investigate controlled hemispheric semantic priming for young healthy adults. Two experiments were employed for a between subjects comparison of time-course differences (stimulus onset asynchrony, or SOA, varied between experiments) in hemispheric activation of associated and nonassociated category members. Continuous electroencephalograms were recorded throughout the priming task for each participant, and later analysed with reference to relevant ERP components (N400 and Late Positive Complex). Bilateral N400 priming was revealed for associated category members at both the short and long SOA. There was no significant N400 priming for the nonassociated category member condition. The examination of hemispheric priming of associated and nonassociated category member stimuli over the same time-course was continued in the second study for participants with unilateral LH lesions and matched controls. The second investigation aimed to determine the impact of unilateral LH lesions on controlled hemispheric semantic priming, utilising the DVF priming paradigm with participants following unilateral lesions. This study also aimed to explore associations between hemispheric activation during the online priming task and offline comprehension abilities. Differences in priming were observed between the LH lesion group and the control group, with participants in the LH lesion group requiring the association relationship to elicit priming. Priming also varied for participants as a function of their offline comprehension abilities, with RH priming associated with higher offline scores. The third investigation continued the exploration of hemispheric semantic activation following LH lesion, examining the impact of a LH lesion on interhemispheric control mechanisms, and the modification of hemispheric processing capacities with and without dominant hemisphere control. This investigation again utilised DVF priming with associated and nonassociated category member stimuli, in conjunction with the dual task paradigm. The dual task paradigm is designed to overload one hemisphere’s processing resources in order to remove interhemispheric suppression. Findings indicate that following LH lesions, the RH’s contribution is enhanced under conditions that are designed to overload the LH. The final study shifts from the investigation of participants with LH lesions to the impact of a RH lesion. This exploration of controlled hemispheric semantic priming following RH lesion sought to increase our understanding of the underlying mechanisms for semantic processing following unilateral lesion. The RH’s role in lexical-semantic processing has been documented consistently over approximately the last twenty years, however, there remains limited direct investigation of a RH lesion’s impact on contributions to semantic processing. A single case investigation utilised the same experimental procedure as the second study described. Findings suggest a similar activation pattern between the individual with RH lesion and the control participants, with both exhibiting bilateral activation of the associated and nonassociated category member stimuli. However, a subtle difference was found between the activation of the individual with RH lesion and that of the control group, with the individual with a RH lesion showing increased strategic processing difficulties at the longer SOA. Overall, the current thesis demonstrates the importance of the RH for efficient strategic semantic processing for both healthy adults, and people with unilateral lesions. In addition, this thesis concludes that following a LH lesion, the RH contribution to controlled semantic processing may be associated with successful comprehension, and that RH contributions may be improved with the addition of a secondary task designed to overload LH processing. The present thesis provides evidence to support the use of the DVF priming paradigm in the investigation of hemispheric contributions to semantic processing following unilateral lesion. It is anticipated that these findings will improve the current understanding of the underlying hemispheric contributions to lexical-semantics following a unilateral lesion, and will encourage continuing investigation into the RH’s capacity to impact language recovery.

Made available in DSpace on 2014-07-29T15:06:27Z (GMT). No. of bitstreams: 1 ARON PILOTTO BARCO.pdf: 1001493 bytes, checksum: 7fb9d56db2e606604fb9f6e5eae38e4d (MD5) Previous issue date: 2012-09-17 / The aim of this dissertation is to study the constutive theory of space as developed in Edmund s Husserl work Ding und Raum, which include his most complete description of spatial experience. The theory is drawn from the analysis of material thinghood con-stitution, accounted as the most basic level of objectivity. In it, Husserl presents the the-sis that spatiality is co-given in the perception of bodies, specifically for its ability to move, whose multiplicity of possible positions coalesce into a field of possibilities ex-perienced as three-dimensional space. The present study aims to explore this theory as a stage in the context of transcendental phenomenology development that maintains con-nections with the earliest Husserl s incursions in problems concerning geometry and mathematical theory of multiplicities, and also explore some consequences and internal problems of the theory. / O objetivo da dissertação é o estudo da teoria constitutiva do espaço como desenvolvida por Edmund Husserl na obra Ding und Raum, onde consta sua mais completa descrição sobre a experiência espacial. A teoria é extraída da análise da constituição da coisa ma-terial, tida como a objetividade de nível mais básico. Nela, Husserl apresenta a tese de que a espacialidade é co-doada na percepção dos corpos, especificadamente por sua ca-pacidade de movimento, cuja multiplicidade de posições possíveis coalescem em um campo de possibilidades vivenciado como o espaço tridimensional. O presente estudo visa explorar essa teoria como uma etapa no contexto de desenvolvimento da fenomeno-logia transcendental que mantém conexões com as primeiras incursões de Husserl em problemas da geometria e da teoria matemática das multiplicidades, e também explorar algumas consequências e problemas internos da teoria.

Objetivos: Avaliar a integridade das vias magnocelular (M) e parvocelular (P) atraves da percepcao de contraste e avaliar a sensibilidade no campo visual e respostas no ERG multifocal, em pacientes com esclerose multipla. Métodos e Resultados: Foram avaliados 29 pacientes (20F; 9M; idade media = 35,76 }10,91 anos) com diagnostico de esclerose multipla (15 com historico de neurite optica). Todos os pacientes apresentavam acuidade visual entre 0 e 0,1 logMAR. A percepcao de contraste foi avaliada atraves da funcao de sensibilidade ao contraste (programa PSYCHO; Cambridge Research System), com os limiares medidos em 0.2, 0.5, 1.0, 1.9, 5.3, 9.7 e 19.4 ciclos por grau; e do teste do Pedestal (Pokorny & Smith, 1997). O campo visual foi medido com o Campimetro Automatico de Humphrey, algoritmo SITA, estrategia central 24-2. O ERGmf foi registrado, utilizando o sistema VERIS, com 103 hexagonos. A analise foi baseada nos valores de amplitude e latencia de N1 e P1 das respostas de seis regioes predeterminadas de acordo com o mapa sugerido por Garway-Heath et al (2000), para os kernels de primeira e segunda ordem. Os pacientes foram divididos em 2 grupos: NO (antecedente de neurite optica) e SNO (sem antecedente de neurite optica). Resultados: O grupo NO nao diferiu do grupo SNO em nenhum dos testes, exceto nas medidas de amplitude do kernel de segunda ordem no ERGmf (Tukey HSD Test, PostHoc). Todos os pacientes mostraram uma reducao na percepcao de contraste, quando comparados ao grupo controle. Os resultados diferiram significativamente do grupo controle em todas as frequencias espaciais avaliadas na funcao de sensibilidade ao contraste (p < 0.001; ANOVA), e nos dois paradigmas avaliados pelo teste do Pedestal (p <0.05 ANOVA de medidas repetidas). As respostas do kernel de primeira ordem do ERGmf para ambos os grupos, quando comparados com o grupo controle, nao apresentaram diferenca estatistica significativa para as regioes analisadas (p > 0.05; ANOVA de medidas repetidas). As respostas de amplitude dos pacientes, para o kernel de segunda ordem apresentaram-se diferentes do grupo controle, com significancia estatistica para as areas 2, 3, 4, 5 e 6 (p < 0.05; ANOVA de medidas repetidas). Os resultados do campo visual mostraram reducao de sensibilidade nos pacientes em estudo, comparados ao grupo controle, com diferenca estatisticamente significante para todas as regioes (p <0.05; ANOVA de medidas repetidas). Conclusões: Aumento nos limiares de deteccao de contraste foram encontrados nos pacientes com esclerose multipla, em ambos os testes. O padrao de perda nas varias frequencias espaciais e em ambos os paradigmas analisados no teste do Pedestal, sugere um comprometimento nao seletivo das vias visuais, afetando tanto a via parvo como a magnocelular. As alteracoes nas respostas do ERG multifocal detectadas apenas no kernel de segunda ordem poderiam estar relacionadas a danos retrogrados a camada de fibras nervosas da retina causados pela desmielinizacao. Nao foram encontradas correlacoes com as perdas de sensibilidade no campo visual / Purpose: To assess the integrity of the magnocellular (M) and parvocellular (P) pathways by measuring contrast perception and to evaluate the visual field and multifocal ERG responses in patients with multiple sclerosis. Methods: 29 patients (20F, 9M, mean age = 35.76 } 10.91 years) diagnosed with multiple sclerosis were evaluated (15 with optic neuritis). All patients had visual acuity between 0 and 0.1 logMAR. The contrast perception was assessed by the measurement of contrast sensitivity function (program PSYCHO, Cambridge Research System) using spatial frequencies 0.2, 0.5, 1.0, 1.9, 5.3, 9.7 and 19.4 cycles per degree and the pedestal test (Pokorny & Smith, 1997). The visual field was measured using the central 24-2 SITA algorithm of the Humphrey Field Analyzer. The mfERG was recorded using the Veris system with 103 hexagons in which N1 and P1 amplitude and latency values of six predetermined areas according to the map suggested by Garway-Heath et al (2000) were used (first and second order kernels). Patients were divided into two groups: NO (with optic neuritis) and SNO (without optic neuritis). Results: The NO group did not differ from the SNO in any of the tests except for the second order kernel amplitudes in the mfERG (Tukey HSD posthoc test). All patients showed a reduction in contrast perception compared to the control group. The patients results were significantly different from the control groups at all spatial frequencies tested (p <0.001, ANOVA), and for the two paradigms of the pedestal test (p <0.05, ANOVA). The first order kernel responses in the mfERG showed no significant difference for both patient groups when compared with the control group (p> 0.05, ANOVA). The second order kernel amplitudes were different between patients and controls, with statistical significance for areas 2, 3, 4, 5 and 6 (p <0.05, ANOVA). The visual field results showed sensitivity reductions in the patients compared to controls, which was statistically significant for all regions (p <0.05, ANOVA). Conclusions: Increased thresholds for contrast detection were found in patients with multiple sclerosis in both tests. The pattern of loss in the various spatial frequencies and in both test paradigms of the Pedestal suggests a non-selective impairment of the visual pathways affecting both the parvo and magnocellular pathways. Changes in multifocal ERG responses found only in the second order kernel may be related to retrograde damage of the nerve fiber layer of the retina caused by demyelization. No significant correlation with the visual field losses was found

This thesis describes a series of investigations into the use of optic nerve head (ONH) imaging in primary open-angle glaucoma (POAG), and its relation to visual function. Accurate diagnosis is a key issue in POAG, particularly the difficult task of separating those with early disease from those healthy individuals who display signs of POAG. The purpose of this work is to improve diagnostic methods in glaucoma through use of ONH imaging and its relationship with visual field (VF) loss. First, the performance of a group of expert clinicians evaluating ONH photographs for glaucomatous damage was investigated. The results showed that even when their assessments are combined discrimination between eyes with and without POAG (based on VF loss) is far from perfect, highlighting the need for improvements in diagnosis. The possibility of combining structural and functional data to aid diagnosis was then considered. This requires VF loss and ONH damage to be strongly topographically related. The strength of this relationship was evaluated in 185 patients with POAG. 10,000 computer-generated maps between the ONH and VF were tested and the topographic relationship measured with each of these was compared to that using a published structure-based map. The weak topographic relationships found suggest that the application of these maps to individual patients is limited with current measures. The next chapter describes how a multispectral imaging (MSI, also called hyperspectral imaging) system was set-up for spatial evaluation of ONH oxygenation using a Beer-Lambert law model. Test-retest repeatability was tested and found to be acceptable for the purposes of the following studies. The MSI system was then used for an investigation of the relationship between ONH oxygenation and VF loss. 33 eyes of 18 patients underwent VF testing, MSI and HRT3 imaging. Superior-inferior asymmetries in VF sensitivity were compared to superior-inferior asymmetries in ONH oxygenation measured by MSI and in neuroretinal rim (NRR) area measured by HRT3. This way we take advantage of the typical progression of POAG and each eye acts as its own reference, negating the effect of a wide normal range and overlap between health and disease. This study found, for the first time, a strong association between ONH oxygenation and VF sensitivity. A re-analysis of the 33 ONH oxygenation maps was then performed to assess oxygenation only in the area of the NRR as defined by the HRT. Superior-inferior asymmetries in NRR oxygenation were then compared to superior-inferior asymmetries in VF loss, and the associations found were similarly strong. This study shows that MSI is capable of detecting areas of NRR deemed healthy tissue by structural imaging techniques, which are in fact poorly oxygenated and associated with VF defects. These findings show that NRR oxygenation measured by MSI is strongly related to VF loss. This important information complements existing technologies and may aid in the future diagnosis and management of patients with POAG.

Le traitement de l’épilepsie chez le jeune enfant représente un enjeu majeur pour le développement de ce dernier. Chez la grande majorité des enfants atteints de spasmes infantiles et chez plusieurs atteints de crises partielles complexes réfractaires, le vigabatrin (VGB) représente un traitement incontournable. Cette médication, ayant démontré un haut taux d’efficacité chez cette population, semble toutefois mener à une atteinte du champ visuel périphérique souvent asymptomatique. L’évaluation clinique des champs visuels avec la périmétrie chez les patients de moins de neuf ans d’âge développemental est toutefois très difficile, voire impossible. Les études électrophysiologiques classiques menées auprès de la population épileptique pédiatrique suggèrent l’atteinte des structures liées aux cônes de la rétine. Les protocoles standards ne sont toutefois pas spécifiques aux champs visuels et les déficits soulignés ne concordent pas avec l’atteinte périphérique observée. Cette thèse vise donc à élaborer une tâche adaptée à l’évaluation des champs visuels chez les enfants en utilisant un protocole objectif, rapide et spécifique aux champs visuels à partir des potentiels évoqués visuels (PEVs) et à évaluer, à l’aide de cette méthode, les effets neurotoxiques à long terme du VGB chez des enfants épileptiques exposés en bas âge. La validation de la méthode est présentée dans le premier article. La stimulation est constituée de deux cercles concentriques faits de damiers à renversement de phase alternant à différentes fréquences temporelles. La passation de la tâche chez l’adulte permet de constater qu’une seule électrode corticale (Oz) est nécessaire à l’enregistrement simultané des réponses du champ visuel central et périphérique et qu’il est possible de recueillir les réponses électrophysiologiques très rapidement grâces l’utilisation de l’état-stationnaire (steady-state). La comparaison des données d’enfants et d’adultes normaux permet de constater que les réponses recueillies au sein des deux régions visuelles ne dépendent ni de l’âge ni du sexe. Les réponses centrales sont aussi corrélées à l’acuité visuelle. De plus, la validité de cette méthode est corroborée auprès d’adolescents ayant reçu un diagnostic clinique d’un déficit visuel central ou périphérique. En somme, la méthode validée permet d’évaluer adéquatement les champs visuels corticaux central et périphérique simultanément et rapidement, tant chez les adultes que chez les enfants. Le second article de cette thèse porte sur l’évaluation des champs visuels, grâce à la méthode préalablement validée, d’enfants épileptiques exposés au VGB en jeune âge en comparaison avec des enfants épileptiques exposés à d’autres antiépileptiques et à des enfants neurologiquement sains. La méthode a été bonifiée grâce à la variation du contraste et à l’enregistrement simultané de la réponse rétinienne. On trouve que la réponse corticale centrale est diminuée à haut et à moyen contrastes chez les enfants exposés au VGB et à haut contraste chez les enfants exposés à d’autres antiépileptiques. Le gain de contraste est altéré au sein des deux groupes d’enfants épileptiques. Par contre, l’absence de différences entre les deux groupes neurologiquement atteints ne permet pas de faire la distinction entre l’effet de la médication et celui de la maladie. De plus, la réponse rétinienne périphérique est atteinte chez les enfants épileptiques exposés au Sabril® en comparaison avec les enfants neurologiquement sains. La réponse rétinienne périphérique semble liée à la durée d’exposition à la médication. Ces résultats corroborent ceux rapportés dans la littérature. En somme, les résultats de cette thèse offrent une méthode complémentaire, rapide, fiable, objective à celles connues pour l’évaluation des champs visuels chez les enfants. Ils apportent aussi un éclairage nouveau sur les impacts à long terme possibles chez les enfants exposés au VGB dans la petite enfance. / Epilepsy control is a major issue for the normal development in children. For the vast majority of children with infantile spasms and for some with refractory complex partial seizures, vigabatrin (VGB) represents the main treatment. VGB, which have shown high efficiency rate in this population, may, however, induce a peripheral visual field deficit, often asymptomatic. Clinical visual field assessment with perimetry is practically impossible in patients less than nine years of developmental age. Electrophysiological studies in epileptic children suggest an impact on the retinal structures related to the cones. However, standard protocols are not field-specific and the deficits reported in the literature are not coherent with the peripheral deficit observed. Thus, this thesis aims to develop a fast and efficient electrophysiological protocol to examine the visual field’s integrity, which would be useful in pediatric testing and to assess the visual field long-term effects of the VGB in school-aged epileptic children exposed early in life. The first article concerns the method’s validation. The stimulation is made of two high-contrast radial checks reversing at two different temporal frequencies. Adult testing reveals that only one electrode (Oz) is needed to record simultaneously both central and peripheral visual fields and that steady-state use allows fast gathering of both electrophysiological responses. No effect of age or sex was found in the comparison of adult and child’ responses. Moreover, the visual acuity, as calculated by the binocular visual acuity index, was related to the central signal when comparing healthy participants with central visual impaired adolescents. Our method presents several advantages in evaluating visual fields integrity, as it is fast, reliable and efficient, and applicable in children. The aim of the second article of the thesis is the assessment of the long term visual effect on the visual field in children exposed to VGB in infancy in comparison to epileptic children exposed to other antiepileptics and with healthy children using the previously validated electrophysiology method with the addition of contrast variation and simultaneous recording of electroretinograms. Results reveal a cortical central deficit at high and mid-range contrast in VGB exposed-children and at high contrast in other antiepileptic exposed group. The contrast gain is also affected in both epileptic groups. The absence of difference between both epileptic groups does not allow distinguishing the impact of medication and/or seizure disorder. The peripheral retinal response is also altered in the VGB-exposed group in comparison to the healthy group. The peripheral retinal response is related to the exposition duration. This result concurs with previous studies in the literature. Finally, the results of the thesis offer an objective, fast, efficient and alternative method to assess visual fields in children. They also bring a new point of view on the likely long term impacts of the VGB in children exposed in infancy.