As especializações do hemisfério direito (HD) no processamento da função lingüística e da comunicação vêm ganhando destaque na literatura internacional, sendo ainda pouco conhecidas no contexto nacional. Conseqüentemente, há, ainda, limitados procedimentos de avaliação neuropsicológica dos distúrbios comunicativos apresentados em quadros de lesões desse hemisfério. Frente a essa demanda de ferramentas diagnósticas, a presente pesquisa teve por objetivo promover estudos teóricos e empíricos com a Bateria Montréal de Avaliação da Comunicação – Bateria MAC, versão Brasileira do instrumento canadense Protocole Montreal d’Évaluation de la Communication – Protocole MEC, analisando-se o processamento de habilidades comunicativas de ativação do HD em adultos não lesados e em indivíduos com lesão vascular nesse lado do cérebro. Essa tese está composta por quatro estudos teóricos, com os objetivos de verificar quais os indícios do papel do HD no processamento comunicativo em estudos de neuroimagem com indivíduos neurologicamente preservados (Estudo teórico 1), apresentar uma meta-análise de estudos com indivíduos com lesão vascular no HD, investigando-se o desempenho desta população no processamento comunicativo (Estudo teórico 2), apresentar uma revisão teórica sobre a avaliação neuropsicológica da linguagem após lesão cerebral, com ênfase nas avaliações funcionais (Estudo teórico 3) e promover uma caracterização da Síndrome do HD (Estudo teórico 4). Além disso, a tese também está formada por três estudos empíricos, que visam a verificar o efeito de variáveis sócio-demográficas no desempenho comunicativo avaliado pela Bateria MAC (Estudo empírico 1), a apresentar normas de desempenho quanto à idade e à escolaridade, assim como dados da fidedignidade desse instrumento (Estudo empírico 2) e a averiguar o desempenho de lesados de HD nas tarefas comunicativas da Bateria MAC, comparando-os com um grupo controle (Estudo empírico 3). Como resultados, os estudos teóricos 1 e 2 mostraram uma importante contribuição do HD no processamento comunicativo tanto em indivíduos neurologicamente saudáveis quanto em indivíduos com lesões cerebrais direitas. O estudo teórico 3 evidenciou um crescente interesse pelo exame dos aspectos funcionais. O quarto estudo caracterizou os principais sintomas cognitivos (anosognosia, heminegligência sensorial, prosopagnosia, alterações de memória visuo-espacial e de trabalho, dispraxia construtiva e disfunção executiva), comunicativos (alterações nos componentes discursivo, pragmático-inferencial, léxico-semântico e prosódico) e comportamentais (dificuldades de compreensão e produção de emoções faciais e vocais e alterações neuropsiquiátricas) da Síndrome do HD. No estudo empírico 1, foram verificados efeitos das variáveis idade e escolaridade em tarefas dos quatro processamento avaliados pela Bateria MAC, sendo o efeito da educação mais significativo. O estudo empírico 2 apresentou normas quanto à idade e à escolaridade e demonstrou uma adequada fidedignidade do instrumento investigado. Por fim, no estudo 3 observou-se efeito da lesão de HD em tarefas discursivas, pragmáticas, léxico-semânticas e prosódicas, além de uma menor homogeneidade do grupo clínico quando comparado ao controle. / Right hemisphere (RH) specializations related to language and communication functions have been focused in international literature, although they are nationally less known. Consequently, there still are reduced neuropsychological assessment procedures to evaluate communication disorders present in right brain damage. Taking this great demand of diagnosis tools into account, this research aimed to present theoretical and empirical studies with the Brazilian version of Montreal Communication Evaluation Battery – Protocole MEC, analyzing the process of communicative abilities related to RH’s activation in non-damaged adults and in individuals with a stroke in this hemisphere. This thesis is formed by four theoretical studies, with the aims to verify the literature index to right hemisphere role on communicative processing in neuroimaging studies with neurologically normal participants (Theoretical study 1), to present a meta-analysis of studies with right brain damaged participants, verifying their communicative processing (Theoretical study 2), to present a theoretical review about the language neuropsychological assessment after brain damage, emphasizing the functional evaluation (Theoretical study 3) and to promote a description of the RH Syndrome (Theoretical study 4). Moreover, the thesis also includes three empirical investigations, witch aim to verify demographic factors’ effects on communication performance evaluated by Protocole MEC (Empirical study 1), to present norms related to age and education, as well as reliability data (Empirical study 2) and to investigate right brain damaged communication performance in Protocole MEC’s tasks, comparing this clinical group with a control one (Empirical study 3). As results, theoretical studies 1 and 2 showed an important contribution of the right hemisphere to communication process in healthy and right brain damaged subjects. In the theoretical study 3, a growing interest in the evaluation of language functional components was observed. The fourth study characterized the main RH Syndrome’s cognitive symptoms (anosognosia, hemineglect, prosopagnosia, working and visual-spatial memory disorders, constructional dyspraxia and executive dysfunction), communication symptoms (discoursive, pragmatic, lexical-semantic 12 and prosodic deficits) and behavioral symptoms (difficulties in comprehension and production of facial and vocal expression, as well as neuropsychiatric disorders). In the empirical study 1, age and schooling effects were noted in tasks that evaluate the four communication components covered by the Protocole MEC. The education effect was more significant than the age one. The empirical study 2 presented norms stratified by age and education and it showed that Protocole MEC is a reliable instrument. In the study 3, a right brain damage effect was observed in discursive, pragmatic, lexical-semantic and prosodic tasks, followed by a less homogeneous performance of the clinical group compared to the control one.

Abstract In pathologies of the ascending aorta or in congenital heart defects, circulation may be temporarily halted during surgical intervention. This is achieved by operating under deep hypothermic circulatory arrest or under hypothermia combined with isolated perfusion techniques. For deep hypothermic circulatory arrest (DHCA), the patient is cooled below 18°C using an extracorporeal heart-lung machine, and circulation and breathing are stopped. The advantage of hypothermia is that it decreases oxygen and glucose consumption and provides the surgeons the time required to repair complex heart defects. However, there is still a relatively high risk of neurological complications that can affect the quality of life of patients and their families. One of the methods to mitigate ischaemia-reperfusion injury is remote ischaemic preconditioning. In this work, the neuroprotective mechanisms of remote ischaemic preconditioning (RIPC) were studied in acute and surviving chronic animal models. In study I, we used an acute model, and studied the effects of RIPC in cerebral microcirculation using an intravital microscope and samples analysed by transmission electron microscope. In study II, a chronic model was used to evaluate whether the effects of remote ischaemic preconditioning can be seen in the markers of oxidative stress or in redox-regulating enzymes. Study III was conducted to supplement the findings of study II, considering the markers of oxidative stress. Findings in all studies were consistent with one another. Study I showed the effect of remote ischaemic preconditioning on leukocyte activation and adhesion to cerebrocortical vessels in piglets after prolonged DHCA. Additionally, cellular preservation of endoplasmic reticulum was present in transmission electron microscope analysis of the central nervous system. In studies II and III, the remote ischaemic preconditioning lowered markers of ischaemia-reperfusion-related oxidative stress. In study III the remote ischemic preconditioning lowered oxidative stress already during cardiopulmonary bypass. / Tiivistelmä Hoidettaessa nousevan aortan sairauksia ja synnynnäisiä sydänvikoja verenkierto voidaan tilapäisesti pysäyttää kirurgisten toimenpiteiden ajaksi. Tämä saavutetaan jäähdyttämällä elimistö verenkierron pysäytyksen ajaksi tai jäähdytettynä isoloitujen perfuusiotekniikoiden avulla. Potilas jäähdytetään alle 18 °C lämpötilaan käyttäen kehonulkoista sydän-keuhkokonetta, minkä jälkeen verenkierto ja hengitys voidaan väliaikaisesti pysäyttää. Elimistön viilentäminen vähentää hapen ja glukoosin kulutusta ja antaa kirurgeille aikaa korjata monimutkaisia sydänsairauksia. Verenkierron pysäytyksestä ja palauttamisesta voi ilmaantua keskushermostoon iskemia-reperfuusiovaurioita, mitkä vaikuttavat potilaiden ja heidän läheistensä elämänlaatuun. Esialtistava raajaiskemia on yksi tutkituista menetelmistä lieventää iskemia-reperfuusiovauriota. Tässä työssä esialtistavan raajaiskemian hermostoa suojaavia mekanismeja tutkittiin akuutilla ja kroonisilla koe-eläinmalleilla. Tutkimuksessa I tutkimme esialtistavan raajaiskemian vaikutuksia aivojen mikroverenkiertoon kuvaamalla aivojen pintaverisuonia mikroskoopilla, ja hermosoluihin käyttäen läpäisyelektronimikroskooppia. Tutkimuksessa II kroonisella mallilla tutkittiin voiko esialtistavan raajaiskemian vaikutuksia nähdä oksidatiivisen stressin määrässä tai hapetus-pelkistys reaktioita säätelevissä entsyymeissä. Kolmas tutkimus tehtiin toisen tutkimuksen päätelmien täydentämiseksi mitaten oksidatiivista stressiä. Kaikkien osatöiden löydökset olivat keskenään johdonmukaisia. Ensimmäisessä osatyössä esialtistava raajaiskemia vaikutti leukosyyttiaktivaatioon ja leukosyyttien tarttumiseen aivojen pintaverisuoniin pidennetyn hypotermisen verenkierron seisautuksen jälkeen. Myös hermosolujen sisäisten soluelinten säilyminen näkyi läpäisyelektronimikroskoopilla raajaiskemiaryhmällä. Tutkimuksissa II ja III esialtistava raajaiskemian todettiin alentavan iskemia-reperfuusion aiheuttamaa oksidatiivista stressiä, jonka todettiin tapahtuvan/alkavan jo sydän-keuhkokoneen käytön aikana tutkimuksen III perusteella.

This final thesis covers the basics of artificial neural networks, with focus on supervised learning, pruning and the problem of achieving good generalization ability. An empirical investigation is conducted on twelve dierent problems originating from the Proben1 benchmark collection.The results indicate that pruning is more likely to improve generalization if the data is sensitive to overtting or if the networks are likely to be trapped in local minima.

The study investigated the long-term neuropsychological effects of repetitive mild traumatic brain injury (MTBI) due to participation in a contact sport amongst South African final year male high school athletes (N=189). The sample was divided by sports affiliation (Contact n = 115; Non-Contact n = 74) and concussion history (2+ Concussion n = 43; 0 Concussion n = 108). Comparative subgroups were statistically equivalent for age, education and estimated IQ (P > 0.05), with the Contact sport groups having markedly higher incidences of concussion than controls (p < 0.000). Measures included the ImPACT Verbal and Visual Memory, Visuomotor Speed and Reaction Time Composites, Digit Symbol Substitution and Digit Symbol Incidental Recall (immediate and delayed), the ImPACT Symptom Scale and a Post-concussion Symptom (PCS) questionnaire. Independent t-tests on cognitive measures at pre-and post-season revealed a predominant trend of Contact and 2+ Concussion groups performing worse, although only ImPACT Reaction Time at pre-season reached significance (p = 0.014). PCS comparisons revealed an overwhelming tendency of enhanced symptoms for Contact and 2+ Concussion groups with total scores being significantly different in most instances at pre-and post-season. Fatigue and aggression were the symptoms most pervasively high for the Contact and 2+ Concussion groups. Dependent t-test analyses at pre- versus post-season, revealed significant practice effects for the Contact group, not in evidence for controls on ImPACT Visual Motor Speed and Digit Symbol Incidental Recall-Delayed. Overall the results imply the possible presence of lingering neurocognitive and symptomatic concussion sequelae amongst South African final year high school participants of a contact sport. The indications gain potency when understood against the background of (i) Brain Reserve Capacity threshold theory, and (ii) the known risk of Type II error in group MTBI research, that might result in under-emphasis of subtle effects and miscalculation of cost-benefit risks. Clinical implications, and the need for prospective case-based research to ratify the results of this predominantly cross-sectional study, are discussed.

Pharmacological interventions to treat Human Immunodeficiency Virus (HIV) with antiretrovirals (ARVs), have dramatically improved the survival rates of HIV positive children maturing into adulthood. However, HIV-associated neurocognitive decline still persists in the era of ARVs. Within the framework of brain plasticity, a number of researchers have begun to assess the feasibility of cognitive rehabilitation therapy as a complement to ARVs to reverse neurocognitive decline as a result of HIV (e.g., Becker et al., 2012). Only one study has been conducted in South Africa, by Zondo & Mulder (2014), assessing the efficacy of cognitive rehabilitation in a paediatric sample. The current research builds on the above mentioned study by implementing an experimental approach to examine the effect of cognitive rehabilitation in a sample of both HIV positive and HIV negative children. Five HIV positive and six HIV negative children were assigned to either an experimental or control group. The experimental group underwent two months of cognitive rehabilitation therapy remediating sustained attention, whereas the control group took part in placebo activities. Sustained attention measures were taken before and after the intervention training sessions, using a sustained attention subtest from the Test of Everyday Attention for Children (TEA-CH). A Mann Whitney U Test revealed that the experimental group (Mdn=38.50) did not differ significantly from the control group (Mdn = 37.00) after the cognitive rehabilitation intervention, U=12.00, z= -.55, p= .66, r= -.17. But a Wilcoxon Signed Rank Test found that there was a significant improvement from pretest scores (Mdn=31.00) to posttest scores (Mdn=38.00) following the rehabilitation for HIV positive participants in the sample, T=15.00, z = -2.02, p= .04, r= -.90. This raises the possibility that cognitive rehabilitation could be used as a low cost intervention in underdeveloped contexts

La thèse présentée a pour objectif d’analyser dans le cadre de l’approche dynamique du contrôle moteur la coordination motrice de participants sains et cérébrolésés évoluant sur un nouvel outil de rééducation, le cheval mécanique. L’analyse de ces coordinations spontanément adoptées par les individus sur ce cheval, ou modifiées suite à l’apprentissage d’une nouvelle coordination grâce à l’ajout d’un biofeedback visuel en temps réel, conduit à participer à (i) déterminer l’utilité du biofeedback dans ce type de tâche et (ii) à évaluer l’intérêt d’un protocole de 24 séances prescrites par nos soins et réalisées sur cet outil. L’objectif final est alors de participer à l’élaboration d’un protocole de rééducation posturale pour une population de patients cérébrolésés. La première étude a permis de mettre en avant le rôle joué par l’expertise dans l’évolution des coordinations posturales des individus sur le cheval mécanique amenant les cavalières expertes vers une coordination posturale plus adaptée (i.e. maintien des patterns en phase et en antiphase), en comparaison aux novices. Par ces analyses, la coordination tronc/cheval mesurée en antiphase, a été mise en lumière, correspondant ainsi à la coordination retrouvée dans l’activité équestre réelle. Par ailleurs, la mise en place d’une méthode d’apprentissage (étude 2) a permis de modifier le comportement postural des individus après seulement 3 séances, selon les conditions d’apprentissage prescrites. La fréquence d’oscillation du cheval avait un impact important sur la coordination des participants, qui adoptaient une coordination en antiphase (fort attracteur) lorsque la contrainte environnementale était élevée. Toutefois, ces observations n’ont pas permis de démontrer le réel intérêt de l’ajout d’un biofeedback visuel dans l’apprentissage d’une nouvelle coordination posturale chez des sujets sains. Enfin, la troisième étude réalisée chez des patients cérébrolésés a montré l’intérêt de cette nouvelle méthode de rééducation sur la coordination posturale de ces patients. Après 24 séances, leur coordination était différente de celle du groupe témoin, permettant de mettre en avant leur capacité à s’adapter aux contraintes et à développer des modes de coordinations posturales spécifiques (tronc/cheval en antiphase) à l’activité afin d’optimiser au mieux leur posture. / Rooted in the dynamical system approach of motor control, the aim of this thesis is to analyze the motor coordination of healthy and brain-damaged participants oscillating on a new rehabilitation tool: the mechanical horse. The analysis of spontaneous coordination exhibited by individuals on this horse and the learned coordination adopted after a learning phase provided by the addition of a visual biofeedback allowed (i) to determine the usefulness of biofeedback in learning an oscillating task and (ii) to evaluate the interest of a 24 sessions rehabilitation protocol performed using the mechanical horse. The final goal is to participate to the development of a postural rehabilitation protocol for a population of brain-damaged patients. The first study allowed to highlight the role of expertise in the dynamics of the postural coordination on the mechanical horse bringing the expert riders towards a more adapted postural coordination (i.e. maintaining in phase and antiphase patterns). Through this first analysis, the spontaneous trunk/horse coordination was highlighted as antiphase, corresponding to the coordination found in real equestrian activity. Furthermore, the implementation of a learning method (study 2) allowed to modify the postural behavior of novice riders after only 3 sessions. The oscillation frequency had a significant impact on the coordination of participants who fell in an antiphase coordination (strong attractor) when the environmental constraint was high. However concerning those novice but healthy participants, this experiment did not demonstrate the real value of an additional video feedback during learning of a new postural coordination. Finally, the third study performed in brain-damaged patients showed the interest of this new rehabilitation method on the postural coordination of these patients. After 24 sessions, their coordination was different from the one of the control group, allowing to highlight their ability to adapt of constraints and to develop specific modes of postural coordination (trunk/horse antiphase) in order to optimize their posture.

Traumatic brain injury (TBI) incidence rates are increasing among the U.S. population and represent substantial acute and chronic care costs. A confounding factor in TBI treatment is the incidence rates of concomitant mental health disorders including depression, anxiety, and posttraumatic stress disorder (PTSD). Clinical data establish that the prevalence of any of these 3 diagnoses complicates the treatment of TBI regardless of whether the diagnosis was pre-existing or occurred because of the TBI, such that prognosis and recovery are negatively impacted. Despite this evidence, psychological assessment is not a first line step in the approach to TBI. The purpose of this research was to assess the prevalence of psychological screening among TBI patients for depression, anxiety, and PTSD to enable conclusions about the current standard of care in TBI management. Meta-analysis of peer reviewed journals on TBI management was used to determine if there was considerable evidence to support that depression, anxiety, and PTSD were being addressed as the standard of care in TBI management. Mean analysis of literature search results established that there was not considerable evidence to support a conclusion that depression, anxiety, and PTSD assessment were standard of care in TBI management. Among the recommendations resulting from this finding were for additional studies on TBI points of care to determine how mental health is currently being managed among TBI patients, and for a change in current TBI treatment protocols to incorporate mental health assessment as part of overall TBI management. If these, and the remaining recommendations, were implemented, it was affirmed that these would have a positive social impact resulting in improved patient outcomes, decreased healthcare costs, and better healthcare delivery for TBI patients.

The development of emergency department medical interventions and the implementation of fast-transport trauma systems has decreased the rate of death resulting from traumatic brain injury (TBI). Without corresponding methods for long-term treatment and recovery, the prevalence of people disabled by TBI has increased, creating a growing public health problem. Investigations generated by physicians, rehabilitation programs, and social scientists, which attempt to associate standard measures of injury severity with outcome, leave unexplained variance in long-term functional status for persons with TBI. The purpose of this investigation was to use persons with brain injury and their family members, to guide an analysis of the factors that foster successful recovery from brain injury. Three studies were conducted. In Study #1, the method for observation generated by Kurt Goldstein (1934) was adopted to conduct 20 case studies of persons who sustained brain injury. The Schema of the EsEx Couple (Maynard. 1992) was used to orient the investigation. The EsEx Couple Schema proposes that events in human life must be understood by considering the whole system of Person (Essence) in the Environment (Exchange), and the transactions that flow in a recursive loop from Person to Environment and back. Kurt Goldstein's Laws of Organismic Life (1934), a model consistent with that of the EsEx Couple, was used to evaluate the data. Strong patterns associated family and social networks, autonomy, and perceived self-determination with higher levels of recovery, and were used to generate a Model for Recovery. In Study #2. the Motivational Analysis of Self-Systems Processes (Connell & Wellborn, 1991) was combined with results from Study #1 to generate a Development Model, and to build a survey which was administered to 248 persons with brain injury. Results (1) confirmed the model, indicating factors that contribute to recovery were hypothesized measures of Social Context, Perception, and Engagement; and (2) established a valid instrument, generated by persons with brain injury and their families, for measuring functional status. In Study #3. results of the survey research were used to return to the case studies to consider where individual lives differ from expected patterns, and why. Deviations from expected patterns were explored to identify how individual differences operate to affect outcome. Recommendations for clinical practice include (1) directing interventions toward family as well as patient, as a method of enhancing the Social Context for the patient, and (2) using careful evaluation of each patient's idiosyncrasies to consider individual interventions.

Diffusion tensor imaging (DTI) is a specialist MRI modality that can identify microstructural changes or abnormalities in the brain. It can also be used to show fibre tract pathways. Both of these features were used in this thesis. Firstly, standard imaging analysis techniques were used to study the effects of mild, repetitive closed head injury on a group of professional boxers. Such data is extremely rare, so the findings of regions of brain abnormalities in the boxers are important, adding to the body of knowledge about more severe traumatic brain injury. The author developed a novel multivariate analysis technique which was used on the same data. This new technique proved to be more sensitive than the standard univariate methods commonly used. An important part of diagnosing and monitoring brain damage involves the use of biomarkers. A novel investigation of whether diffusion parameters obtained from DTI data could serve as bio-markers of cognitive impairment in Parkinson's disease was conducted. This also involved developing a multivariate approach, which displayed increased sensitivity compared with any of the component parameters used singly, and suggested these diffusion measures could be robust bio-markers of cognitive impairment. Fibre tract connectivity between regions of the brain is also a potentially valuable measure for diagnosis and monitoring brain integrity. The feasibility of this was investigated in a multi-modal MRI study. Functional MRI (fMRI) identifies regions of activation associated with a particular task. DTI can then find the pathway of the fibre bundles connecting these regions. The feasibility of using regional connectivity to interrogate brain integrity was investigated using a single healthy volunteer. Fibre pathways between regions activated and deactivated by a working memory paradigm were determined. Though the results are only preliminary, they suggest that this line of research should be continued.

Children with a recent history of TBI often demonstrate impaired memory, which can be affected by impaired attention, processing speed or impaired verbal information processing. The purpose of this study was to determine if qualitative differences exist among the narrative recall of TBI patients that is not adequately accounted for by standard scoring methods. Sixty-six TBI subjects ranging in age from 6 to 16 were given the Wide Range and Memory and Learning (WRAML) Story Memory subtest and selected subtests from the Wechsler Intelligence Scale for Children - Third Edition (WISC-III). Mean elapsed time since injury was 53 days. Recall of the story on the WRAML subtest was hand-recorded by the examiner. A supplemental scoring method accounted for differences in length, errors, and disorganization. Comparisons were made to a randomly selected control group consisting of 16 hospitalized subjects between 7 and 15 years with no history of head injury, neurological condition or event. Findings suggest the WRAML Story Memory subtest is relatively robust in providing information regarding the quality of recall, with the exception of not accounting for the addition of erroneous details. Subjects with both cortical and subcortical injuries were more likely to add superfluous details to their stories. Results also demonstrated significant differences between the TBI subjects and control group in how well the stories were recalled, primarily in the order of details recalled and in retention after a 30 minute delay. Location was not a significant predictor of narrative organization. Although using this comprehensive supplemental scoring system a regular basis has practical limitations, hand-recording the narrative takes relatively little time and does appear to provide useful additional information concerning the nature of the child's verbal memory difficulties. Furthermore, the more knowledgeable the child, parents and teacher are about these difficulties and about remediation strategies, the more likely the child will have a successful learning experience upon return to the classroom.