Spatial neglect has mainly been described through its spatial deficits (such as attentional bias, disengagement deficit or exploratory motor behavior), but numerous other studies have reported non-spatial impairments in patients suffering from this disorder. In the present thesis, non-spatial deficits in neglect are hypothesized to form a core impairment, which can be summarized as a difficulty to learn and benefit from regularities in the environment. The different studies conducted and reported in the present thesis have converged to support this hypothesis that neglect patients have difficulty to interact with environmental statistics. The two first studies, which tested the visual modality (Chapters 2 and 3), have demonstrated that neglect patients have difficulties to become faster to respond to targets that appear successively at the same location (position priming). This difficulty is also more generic, as neglect patients do not learn that some things occur more often than others, such as for example that a target has a high probability to be repeated at a specific region. Those two studies have shown that neglect patients are impaired in position priming and statistical learning, which corresponds to difficulties benefiting from regularities presented in the visual domain. This difficulty may be explained by patients’ impairment in working memory or temporal processing. Several studies have reported the implication of those two mechanism in statistical learning: if patients tend to underestimate the time that a target is presented on the screen and have difficulties keeping in memory its precedent location, this translates into a difficulty to benefit from the repeats of the target position as well as a difficulty to benefit from transition probability. In order to verify if priming and statistical learning impairments were specific to the visual modality or if neglect patients present a multimodal difficulty to learn the transition probability in general, brain damaged patients were tested in the auditory domain (Chapter 5), with a paradigm that has shown statistical learning in infants. This study confirmed that for the auditory modality too, brain damaged patients are impaired in statistical learning. The different results of the studies reported in Chapters 2, 3, 4 and 5 converge to support the hypothesis that spatial neglect patients have difficulties benefiting from regularities of their environment. Nevertheless, this impairment is not irreversible, as it was demonstrated by a chronic neglect patient who was trained with three sessions distributed over three days (Chapter 2). Although having similar results to the other patients for the first session, this patients’ performance improved over the sessions to show a faster reaction time for the targets presented on the high probability region (his contralesional side). Therefore, priming and statistical learning investigated in this thesis are worth exploring further for their potential outcome in the rehabilitation domain.

The aim of this review is to provide a unified perspective of unilateral spatial neglect (USN). USN is a neurological disorder frequently observed following damage or diseases to the brain. It is particularly associated with strokes to specific anatomical structures within the right hemisphere. Patients with USN fail to respond to or orient towards stimuli located in the hemispace contralateral to the lesion. They also show peculiar behavioral manifestations. There are several distinct subtypes of USN which can affect sensory or motor modalities, spatial representations, the range of space, or pure imagery. This disorder can appear in any sensory modality but the majority of studies have investigated the visual aspect of USN in these subtypes. Theoretical proposals are supported by empirical evidence deriving from neuroimaging which distinguish between these subtypes of USN. Thus, the heterogeneity of the disorder is evident and clinical assessment methods face great difficulties while prevalence rates vary. The neural pathways of spatial attention distinguish between the ventral and dorsal visual streams, both with distinct functional roles and anatomical bases. Prism adaptation (PA) is a common rehabilitation technique among many others and has shown positive effects on USN while having some limitations. A general discussion and concluding remarks are presented in the final section followed by future research suggestions.

Body schema is indispensable for sensorimotor control and learning, but it remains unclear whether it is associated with cognitive functions. Data from patients with spatial neglect support this view; yet observations in healthy participants are inconsistent. Here I conducted two sets of experiments examining influences of trunk position: the first probed attention and spatial working memory using a change detection task and a two-back task; the second used different versions of the Posner paradigm to examine whether head-on-trunk position governs disengagement of attention. In none of the experiments did I observe that trunk turns altered performance in the left versus right visual field in an ipsiversive fashion as reported in neglect. Nevertheless, I found that trunk-right position improved performance at eccentric locations of the visual field. The data are inconsistent with previous findings of head-on-trunk effects in normal participants. Further studies are required to clarify these discrepancies.

Body schema is indispensable for sensorimotor control and learning, but it remains unclear whether it is associated with cognitive functions. Data from patients with spatial neglect support this view; yet observations in healthy participants are inconsistent. Here I conducted two sets of experiments examining influences of trunk position: the first probed attention and spatial working memory using a change detection task and a two-back task; the second used different versions of the Posner paradigm to examine whether head-on-trunk position governs disengagement of attention. In none of the experiments did I observe that trunk turns altered performance in the left versus right visual field in an ipsiversive fashion as reported in neglect. Nevertheless, I found that trunk-right position improved performance at eccentric locations of the visual field. The data are inconsistent with previous findings of head-on-trunk effects in normal participants. Further studies are required to clarify these discrepancies.

Submitted by CARLOS LEONARDO SACOMANI MARQUES (leonardomarques.fisioterapia@hotmail.com) on 2018-06-28T16:51:13Z No. of bitstreams: 1 Dissertacao Leonardo.pdf: 2058689 bytes, checksum: 1f1881acaef2c1dbbf01a2e66d1a0564 (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-06-28T18:23:32Z (GMT) No. of bitstreams: 1 marques_cls_me_bot.pdf: 2058689 bytes, checksum: 1f1881acaef2c1dbbf01a2e66d1a0564 (MD5) / Made available in DSpace on 2018-06-28T18:23:32Z (GMT). No. of bitstreams: 1 marques_cls_me_bot.pdf: 2058689 bytes, checksum: 1f1881acaef2c1dbbf01a2e66d1a0564 (MD5) Previous issue date: 2018-06-28 / Introdução: A negligência espacial unilateral (NEU) é uma manifestação prevalente entre os pacientes com acidente vascular cerebral, porém seu diagnóstico é difícil e sua mensuração e repercussão na vida do paciente carecem de métodos de avaliação. A escala de Catherine Bergego tem por objetivo mensurar esse acometimento e o impacto no cotidiano do paciente. Não há validação desta escala na população brasileira. Objetivo: Avaliar a confiabilidade, compreensão e aceitação da versão em português da escala CBS em paciente com diagnóstico clínico de negligência espacial unilateral após Acidente Vascular Cerebral. Método: CBS foi traduzida, culturalmente adaptada e aplicada por dois investigadores independentes. O estudo foi transversal, em 22 pacientes após AVC confirmado por neuroimagem, tomografia de crânio e/ou ressonância de encéfalo. tomografia computadorizada. Além da CBS, foi aplicada a NHISS na entrada do paciente no hospital e no momento da avaliação da CBS, a BIT para diagnóstico da NEU e Barthel. A consistência e coerência foram analisados por meio de α-Cronbach, confiabilidade interobservador por meio do Kappa e a correlação entre as escalas de CBS, BIT mRS, NIHSS e Barthel por meio do coeficiente de Pearson. Resultados: Foram avaliados 22 pacientes sendo encontrado consistência e coerência de  = 0,913, obtendo excelente consistência. Em análise de reprodutibilidade interobservador através do Coeficiente de Kappa, a escala para os 10 itens, mostrou uma confiabilidade razoável e alta entre os avaliadores. A CBS apresentou correlação negativa em comparação com á BIT, sendo que a taxa de concordância interobservador não diferiu significativamente entre as escalas. O resultado da correlação de Pearson realizada entre CBS e BIT foi de 0.03 para o avaliador 1 e 0.03 para o avaliador 2. Além da baixa correlação citada, não obtivemos boa correlação entre os demais escores das escalas de NIHSS, Barthel e Rankin, analisados através do coeficiente de Pearson. Conclusão: A CBS é adequada e validada para estudar pacientes com NEU após AVC em uma população brasileira, multicultural e de língua portuguesa. / Introduction: spatial unilateral neglect (SUN) is a prevalent clinical manifestation in stroke patients, however its diagnosis is difficult, also mensuration and repercussion in patients’ life lacks evaluation methods. Catherine Bergego’s scale (CBS) has the objective of evaluate the impact in quotidian life. There is no validation fo r this scale in Brazilian population. Objective: evaluate confiability, comprehension and acceptation of the Portuguese version of CBS for patients with clinical diagnosis of SUN after stroke. Methods: CBS was translated, culturaly adapted and applied by two independent investigators. It’s a transversal study that evaluated 22 patients with stroke diagnosis confirmed by computed tomography, and a previous score in modified Rankin (mRs) scale of 0. Besides CBS there was application of the National Institute of Health Stroke Scale (NIHSS) at patients’ admission. Together with the CBS the Behaviour Innatention Test (BIT) was applied for NEU diagnosis, and Bartel scale for independency in daily life. Consistency and consistency were analyzed using α-Cronbach, inter-observer reliability using Kappa and the correlation between the CBS, BIT mRS, NIHSS and Barthel scales using the Pearson coefficient. Results: Twenty-two patients were evaluated and was observed consistency and coherence of  = 0.913. In the intra-observer reproducibility analysis using the Kappa Coefficient, the scale for the 10 items showed a reasonable and high reliability among the evaluators. CBS had a negative correlation compared to BIT, and the inter-observer agreement rate did not differ significantly between scales. The result of the Pearson correlation between CBS and BIT was 0.03 for the evaluator 1 and 0.03 for the evaluator 2. In addition to the low correlation, we did not obtain a good correlation between the NIHSS, Barthel and Rankin, analyzed using the Pearson coefficient. Conclusion: CBS is adequate and validated to study patients with SUN after stroke in a Brazilian, multicultural and of Portuguese language.

Orientador: Rodrigo Bazan / Resumo: Introdução: A negligência espacial unilateral (NEU) é uma manifestação prevalente entre os pacientes com acidente vascular cerebral, porém seu diagnóstico é difícil e sua mensuração e repercussão na vida do paciente carecem de métodos de avaliação. A escala de Catherine Bergego tem por objetivo mensurar esse acometimento e o impacto no cotidiano do paciente. Não há validação desta escala na população brasileira. Objetivo: Avaliar a confiabilidade, compreensão e aceitação da versão em português da escala CBS em paciente com diagnóstico clínico de negligência espacial unilateral após Acidente Vascular Cerebral. Método: CBS foi traduzida, culturalmente adaptada e aplicada por dois investigadores independentes. O estudo foi transversal, em 22 pacientes após AVC confirmado por neuroimagem, tomografia de crânio e/ou ressonância de encéfalo. tomografia computadorizada. Além da CBS, foi aplicada a NHISS na entrada do paciente no hospital e no momento da avaliação da CBS, a BIT para diagnóstico da NEU e Barthel. A consistência e coerência foram analisados por meio de α-Cronbach, confiabilidade interobservador por meio do Kappa e a correlação entre as escalas de CBS, BIT mRS, NIHSS e Barthel por meio do coeficiente de Pearson. Resultados: Foram avaliados 22 pacientes sendo encontrado consistência e coerência de  = 0,913, obtendo excelente consistência. Em análise de reprodutibilidade interobservador através do Coeficiente de Kappa, a escala para os 10 itens, mostrou uma confiabilidade... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: spatial unilateral neglect (SUN) is a prevalent clinical manifestation in stroke patients, however its diagnosis is difficult, also mensuration and repercussion in patients’ life lacks evaluation methods. Catherine Bergego’s scale (CBS) has the objective of evaluate the impact in quotidian life. There is no validation fo r this scale in Brazilian population. Objective: evaluate confiability, comprehension and acceptation of the Portuguese version of CBS for patients with clinical diagnosis of SUN after stroke. Methods: CBS was translated, culturaly adapted and applied by two independent investigators. It’s a transversal study that evaluated 22 patients with stroke diagnosis confirmed by computed tomography, and a previous score in modified Rankin (mRs) scale of 0. Besides CBS there was application of the National Institute of Health Stroke Scale (NIHSS) at patients’ admission. Together with the CBS the Behaviour Innatention Test (BIT) was applied for NEU diagnosis, and Bartel scale for independency in daily life. Consistency and consistency were analyzed using α-Cronbach, inter-observer reliability using Kappa and the correlation between the CBS, BIT mRS, NIHSS and Barthel scales using the Pearson coefficient. Results: Twenty-two patients were evaluated and was observed consistency and coherence of  = 0.913. In the intra-observer reproducibility analysis using the Kappa Coefficient, the scale for the 10 items showed a reasonable and high reliability among the e... (Complete abstract click electronic access below) / Mestre

Background: Approximately a third of all stroke patients develop spatial neglect, a debilitating symptom associated with poor outcome. Spatial neglect is clinically defined as a deficit in processing and responding to stimuli presented on the contralesional side of the body, or the space surrounding that side of the body. The heterogenetic, multi-sensory nature of the symptoms renders it difficult to diagnose and treat; therefor effective methods for screening and intervention for neglect are needed. Virtual reality (VR) is a method of brain–computer interaction that involves realtime simulation of an environment, scenario or activity that allows for user interaction and targets multiple senses. We hypothesize that VR can facilitate identification of spatial neglect in stroke patients and that training with this interface will improve patient’s functional outcome, through stimulation to neuronal networks including those controlling attention. Objective: The objective was to construct and validate a computerized test battery for spatial neglect and to investigate its usability in stroke patients. Also to design and develop a VR rehabilitation method for spatial neglect and to evaluate its effects on spatial attention and on neuronal activity in the brain. Method: We designed, developed and evaluated a new concept for assessment (VR-DiSTRO®) and training (RehAtt®) of spatial attention, using VR technology. The hardware consisted of a PC, monitor, 3D-glasses and a force feedback device to control the tasks (i.e., a robotic pen). The software enabled targets to be moved, rotated and manipulated in the 3D environment using the robotic pen. RehAtt® made it possible to combine intense visual scanning training, multi-sensory stimulation (i.e., audio, visual, tactile) and sensory-motor activation of the contralesional arm. In a first study on 31 stroke patients we performed a construct validation of VR-DiSTRO® against Rivermead Behavioural Test Battery (BIT) and investigated the usability. In a second study, 15 subjects with chronic spatial neglect (symptoms >6 month) had self-training, 3 x 1 hour for 5 weeks using RehAtt®. Outcome were measured by changes in neglect tests and in Cathrine Bergego Scale (CBS). Training-related changes in neuronal activity of the brain was studied using fMRI during task and in resting state. Results: VR-DiSTRO® correctly identified all patients with neglect. The sensitivity was 100% and the specificity 82% for VR-DiSTRO® compared to BIT. Usability was high and no side-effects were noted. Using repeated measurement analysis, improvements due to the RehAtt® intervention were found for Baking tray task (p < 0.001), Star cancellation test (p = 0.006) and Extinction test (p = 0.05). Improvements were also seen in the Posner task as fewer missed targets (p = 0.024). Improvement in activities of daily living (CBS) was shown immediately after training (p < 0.01) and patients still reported improvement at 6 months follow-up. Trainingrelated changes in neuronal activity were seen as an increased task-evoked brain activity in prefrontal and temporal cortex, mainly outside the attention network but in related cortical areas. During resting state, changes in network connectivity were seen after intervention with RehAtt® in the Dorsal Attention Network (DAN) and interhemispheric connectivity. Conclusion: VR-DiSTRO® identified visuospatial neglect in stroke patients quickly and with a high accuracy. RehAtt® training improved in spatial attention in chronic neglect with transfer to functions in daily living. Increased neuronal brain activity was found in and between attention networks and related brain structures. This could represent a compensatory effect in addition to sign of a restorative effect from the RehAtt training. The results obtained in this study are promising, encourage further development of the methods and merit for further studies.

The thesis focuses on the issue of spatial neglect and its neuropsychological diagnostics. The theoretical part of the thesis first summarizes recent knowledge about the neglect and offers its classification, which maps the heterogeneous nature of the disorder. Furthermore, two areas of diagnostic methods aimed at neglect detection are discussed, which are the classic "paper-pencil" tests and functional tests. Finally, these methodological areas are put into relationship, the work discusses their possible complementarity and also their use in clinical practice. In the empirical part we focus on selected classic methods and their ability to diagnose mild neglect in the Czech population. For 64 patients, we compared the sensitivity of the Bells test, the line bisection test, and the scene copying test using different criteria. We also examined double dissociations and relationships between tests, and then the relationships between the ability of instruments to detect neglect and the characteristics of probands. The results mostly confirmed the findings of the theoretical part of the thesis. The sensitivity of the methods was low and variable, there were double dissociations between the line bisection test and the other tests, and there were practically no statistically significant correlations...

La perception de la verticale repose sur l’intégration des informations vestibulaires, visuelles et somesthésiques. Elle est généralement étudiée dans la modalité visuelle (VVS) ou haptique (VHS) et plus rarement dans la modalité visuo-haptique (VVHS). Cette modalité pose la question de l’intégration des informations mises en jeu par ces deux modalités dans la perception multimodale et du modèle cognitif sous-jacent. Se pose également la question de l'effet des lésions cérébrales perturbant la perception spatiale (hémi-négligence) dans la perception de la verticale.Une comparaison des VVS, VHS et VVHS est réalisée dans les quatre premières études de cette thèse, chez des participants sains jeunes et plus âgés et chez des patients cérébro-lésés droits avecou sans troubles visuo-spatiaux. Les performances observées sont proches de la verticale gravitaire chez les participants sains pour les VVS et VVHS. La VHS (avec la main droite) est déviée, dans le sens horaire chez les jeunes participants et anti-horaire pour les participants plus âgés. La présence d’un cadre visuel perturbe les VVS et VVHS chez les participants dépendants à l'égard du champ.Les patients cérébro-lésés droits présentent une déviation anti-horaire des trois verticales, plus marquée pour la VHS. Les VVHS mesurées sont correctement prédites, dans toutes les conditions,par la somme des VVS et VHS pondérées par leurs précisions relatives. La variance de la VVHS est moindre que les variances des VVS et VHS. La VHS, systématiquement déviée dans ces quatre premières études, fait l’objet d’une évaluation détaillée dans les deux dernières études de cette thèse. Les résultats montrent que la VHS est déviée dans le sens horaire avec la main droite, dans le sens anti-horaire avec la main gauche chez les participants sains jeunes ; les déviations s’inversent avec l’âge. Par ailleurs, les performances sont systématiquement déviées dans le sens des positions initiales. Considérés ensemble, ces résultats montrent que la perception de la verticale implique les informations mises en jeu par les modalités visuelle et haptique mais avec une prépondérance de la première. Ce travail de thèse montre ainsi que la perception de la verticale subjective repose sur une intégration multimodale pondérée des informations sensorielles en accord avec le modèle statistique bayésien du maximum de vraisemblance. Ce mode d'intégration multi-sensorielle n'est pas altéré par l’âge ou la présence de lésions cérébrales affectant la perception visuo-spatiale. Plusieurs pistes restent à explorer, notamment, le poids de la contribution des informations vestibulaires dans la verticale subjective. / The perception of the vertical direction is achieved through vestibular, visual and somatosensory information integration. It is studied in the visual (SVV), haptic (SHV) and less often in the visuo-haptic modality (SVHV). The latter raises the question of the integration of visual the information involved in the visual and haptic modalities and of the cognitive model underlying this integration. SVV, SHV and SVHV were compared in the first four studies of this thesis, inhealthy young and older subjects and in right-brain damaged patients with or without visuo-spatial disorders. Performances were closed to the gravity in healthy participants, for SVV as well as forSVHV. VHS, assessed with the right hand, was tilted clockwise in young participants and anticlockwise in older participants. The presence of a visual frame disrupted SVV and SVHV. The right-brain damaged patients had an anti-clockwise deviation of SVV and SVHV and the SHV was even more tilted. SVHV was well predicted from the sum of the SVV and SHV weighted by their relative variances in all conditions and the SVHV variances were lesser. SHV was evaluated in detail in the two last studies of this thesis because of the systematic tilt in the first four studies. The results show that the SHV is tilted clockwise with the right hand and anti-clockwise with the left hand in young healthy subjects. Moreover, deviations reversed in older group and performances are systematically tilted toward the initial positions in the two groups. Taken together, these results show that the way participants integrate visual and haptic information fits the maximum like lihoodmodel with a greater weighting of information available in visual modality and that ageing and right-brain lesions does not alter the multisensory integration. The weight of vestibular information in the subjective vertical, which has not been evaluated per se in this thesis, needs further investigations.

Hemispatial neglect, is a major cause of post-stroke disability and poor functional recovery. Hence, identifying sensitive methods to assess and rehabilitate neglect is important. Chapters 3 and 4 focused on development of novel assessment techniques for representational neglect. The 'Shopping Mall' and 'Clock Cueing' tasks improved upon previous tests and were useful in identifying dissociations in representational neglect based on type of stimuli (topological, non-topological) and time of assessment (pre-stroke, post-stroke) in chronic stroke patients. Chapters 5 and 6 investigated the efficacy of offline inhibitory repetitive Transcranial Magnetic Stimulation (rTMS) in producing short (<1 month) and long term (>6 months) changes in visual neglect behaviour. Overall, the findings from these chapters were limited due to lack of sufficient power. After controlling for the effect of baseline performance, the Intervention group's Activities of Daily Living scores significantly improved in the short-term post rTMS, as compared to the Control group. The fMRI task attempted to recruit attention-based top down modulation of sensory activity. It revealed relative hypoactivation of the right occipital lobe in the four left neglect patients tested, both pre and post rTMS, when compared to elderly controls. Chapter 7 explored cognitive predictors of spatial and object neglect in the sub-acute stage after controlling for demographic and stroke related factors, using multivariate blocked logistic regressions. Cognitive performance indicative of spatial attention and selective attention to local features predicted both spatial and object neglect. In addition, coding of spatial relations between features also predicted spatial neglect. Suggestions for combining neglect rehabilitation techniques to target these cognitive processes are discussed. Overall, this thesis provides novel methods to improve representational neglect assessment and highlights the importance of ancillary cognitive domains in contributing to both representational and visual neglect. The rTMS research provides study design-related insights to incorporate in future studies with larger patient samples.