Hemisferectomia unilateral na vida adulta como modelo para o estudo das assimetrias motoras em camundongos

Em humanos, uma série de estudos vem sugerindo que o hemisfério esquerdo é particularmente importante no controle e execução de movimentos. De modo geral, lesões no hemisfério esquerdo promovem déficits motores mais pronunciados que lesões semelhantes no hemisfério direito. Neste trabalho utilizamos a hemisferectomia unilateral para avaliar a contribuição de cada hemisfério na função motora em camundongos. Camundongos Suíços adultos foram submetidos a hemisferectomia unilateral direita (HD) ou esquerda (HE) ou aos procedimentos de controle. Quinze dias após cirurgia, a coordenação motora de cada animal foi avaliada no teste da locomoção forçada em cilindro giratório (Rotarod). A latência para a queda do grupo controle foi significativamente maior que a do grupo HD e não diferiu da do grupo HE. Para auxiliar a interpretação dos resultados obtidos no ROTAROD, uma parte dos animais foi submetida a uma bateria adicional de testes comportamentais na seguinte seqüência: teste de campo aberto, avaliação qualitativa da assimetria sensório-motora, teste da grade elevada e teste de suspensão pela cauda. De modo interessante, no teste da grade elevada, enquanto o grupo HD apresentou o desempenho da pata traseira esquerda (contralateral à lesão) significativamente pior que o da direita, os grupos Controle e HE não apresentaram diferenças entre as duas patas traseiras. De modo análogo ao observado em humanos, nossos resultados sugerem uma ação assimétrica dos hemisférios cerebrais no controle da função motora em camundongos.

A assimetria funcional inter-hemisférica

A temática da assimetria funcional inter-hemisférica e analisada, neste trabalho, através de uma revisão crítica da literatura concernente aos estudos clínicos e experimentais (realizados tanto com pacientes neurológicos quanto com indivíduos normais) que se mostraram mais significativos para a configuração atual deste campo do saber. Inicialmente são analisados os estudos efetuados com pacientes neurológicos lesados unilateralmente, que forneceram as primeiras evidências sobre uma organização assimétrica dos hemisférios cerebrais. Na medida em que tal assimetria refere-se principalmente aos processos cognitivos, focalizou-se esta análise nos estudos mais significativos realizados sobre os quadros de afasias, apraxias, agnosias e amnésias, diretamente relacionados à problemática da assimetria cerebral. Os estudos empregando a técnica de Wada e com pacientes comissurotomizados foram abordados a seguir procurando-se evidenciar o grande avanço que propiciaram nos conhecimentos concernentes à assimetria funcional inter-hemisférica, quer em termos da caracterização funcional de cada hemisfério cerebral (o que acabou por levar a substituição da problemática de dominância cerebral pela de assimetria funcional inter-hemisférica) quer em termos da mobilização de interesse por esta área da pesquisa neuropsicológica. No que concerne aos estudos com indivíduos normais, procurou-se enfatizar a progressão de um enfoque centrado nas caracterizações hemisféricas para um enfoque centrado na análi¬se dos requerimentos cognitivos de uma determinada tarefa, com o objetivo de avaliar a participação relativa dos hemisférios cerebrais nas tarefas complexas. As diferenças individuais quanto ao padrão de lateralização funcional foram particularmente examinadas em relação aos estudos vinculados a variáveis comportamentais facilmente observáveis tais como a preferência manipulatória e sua história familiar, a preferência ocular e o sexo, dando-se ênfase a estudos correlacionais entre aquela primeira variável e a lateralização para a linguagem, que têm tido maior suporte empírico. Os principais modelos emergentes na literatura sobre a atuação conjunta dos hemisférios cerebrais, tentando explicar sua din5mica, foram objeto de um tópico ulterior. Dentre os diversos modelos propostos considerou-se mais consistente o de Dimond e Beaumont (Beaumont, 1974) que propõe uma atuação mais integrada entre os hemisférios cerebrais, embora não se revele totalmente satisfatório. Análises de questões filogenética, ontogenética e referentes aos diferentes processamentos cognitivos requeridos em tarefas complexas foram efetuadas já que constituem grande foco de interesse na literatura atual concernente à assimetria funcional inter-hemisférica.

Padrões de dominância manual, podálica e performance motora em gêmeos

O método de gêmeos envolve a análise diferencial de gêmeos monozigóticos (MZs) e dizigóticos (DZs) a fim de determinar a proporção de variância em um determinado traço atribuível a fatores genéticos e ambientais. Sendo geneticamente idênticos, os gêmeos MZs tendem a apresentar alto índice de concordância em vários atributos comportamentais, enquanto que, os DZs, compartilham 50 % da carga genética, manifestando um reduzido grau de concordância. Todavia, pesquisadores têm investigado possíveis mecanismos genéticos subjacentes do desenvolvimento cerebral para dominância manual e, não têm encontrado utilidade no método de gêmeos, pois, desde 1924, em todos os estudos de dominância manual em gêmeos, a taxa de discordância para o canhotismo e destrimanismo têm sido similares em MZs e DZs. Além disso, frequentemente gêmeos mostram taxa mais alta de prevalência para o canhotismo que os não gêmeos. O objetivo deste estudo foi investigar as possíveis diferenças entre gêmeos destros e canhotos (MZs e DZs combinados) e não gêmeos em variáveis fenótipicas específicas relacionadas à dominância manual, incluindo dominância podálica (chute de penalty), consistência de dominância manual, canhotismo familiar (CF+), postura manual e medidas de habilidades motoras em três testes : Batidas digitais, Tabuleiro de Annett e Pontilhar Pontinhos. Foram avaliados 286 gêmeos ( 255 destros, 34 canhotos) e, 251 não gêmeos (141 destros e 110 canhotos). A análise dos dados revelou o aumento de canhotismo no sexo masculino em três vezes mais do que no feminino. Além disto, destros e canhotos gêmeos foram mais mistos em suas dominâncias manuais e apontaram alta incidência de CF+ entre parentes de primeiro grau que não gêmeos canhotos e destros. Em concordância com estudos anteriores, a frequência de chute contralateral foi mais alta nos mistos do que nos que apresentaram consistência na dominância manual, especialmente entre os canhotos. No que diz respeito à habilidade manual, não foram encontradas diferenças significativas nos três testes de habilidade manual. Conforme as expectativas, destros e canhotos foram mais proficientes na manipulação do estímulo com suas mãos dominantes. Em todas as três medidas, em contraste com os destros, os canhotos (gêmeos e não gêmeos) apresentaram redução entre as assimetrias manuais. Por extensão, o aumento da prevalência de canhotismo entre gêmeos não poderia ser atribuída a influências patológicas, inversão de assimetria ou ordem de nascimento. É possível, levar em consideração, observando a diferença robusta em dominância manual mista que, o padrão de lateralização neuromotora, pode ser mais difusamente organizado nos hemisférios dos gêmeos que em não gêmeos, mas, esta sugestão requer evidência direta, pelo menos a partir de testes de neuro-imagem.

Evaluación de la conectividad cerebral bajo fármacos mediante análisis no lineal del EEG

Màster Oficial en Enginyeria Biomèdica

Mobiliários adaptados para pessoas com paralisia cerebral: um levantamento das teses e dissertações produzidas no Brasil

The Assistive Technology makes the lives of people without disabilities more practical, but for people with disabilities it can make things possible. For these individuals can provide the conditions, making their limitations are not obstacles to their social and personal empowerment, and may contribute to their effective participation in tasks that were previously impossible, such as remaining seated correctly. A segment on which the necessary assistive technology works, is the adaptation of furniture such as chairs, tables, chairs-to-wheels for individuals with disabilities, as well as cerebral palsy. The study aimed to conduct a survey and brief description of theses and dissertations produced in Brazil on furniture adapted for students with cerebral palsy. We made searching in databases of libraries of major universities and federal state national banks, theses and dissertations. Nine studies were selected for description. It was concluded that there is a considerable array of professionals, both in engineering as the field of rehabilitation, to contribute in the adaptation, creation and even the manufacture of furniture for children with cerebral palsy and that the securities most studied are the chairs and their components.

Arterial Spin Labeling Measurements of Cerebral Perfusion Territories in Experimental Ischemic Stroke

Collateral circulation, defined as the supplementary vascular network that maintains cerebral blood flow (CBF) when the main vessels fail, constitutes one important defense mechanism of the brain against ischemic stroke. In the present study, continuous arterial spin labeling (CASL) was used to quantify CBF and obtain perfusion territory maps of the major cerebral arteries in spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) controls. Results show that both WKY and SHR have complementary, yet significantly asymmetric perfusion territories. Right or left dominances were observed in territories of the anterior (ACA), middle and posterior cerebral arteries, and the thalamic artery. Magnetic resonance angiography showed that some of the asymmetries were correlated with variations of the ACA. The leptomeningeal circulation perfusing the outer layers of the cortex was observed as well. Significant and permanent changes in perfusion territories were obtained after temporary occlusion of the right middle cerebral artery in both SHR and WKY, regardless of their particular dominance. However, animals with right dominance presented a larger volume change of the left perfusion territory (23 +/- 9%) than animals with left dominance (7 +/- 5%, P<0.002). The data suggest that animals with contralesional dominance primarily safeguard local CBF values with small changes in contralesional perfusion territory, while animals with ipsilesional dominance show a reversal of dominance and a substantial increase in contralesional perfusion territory. These findings show the usefulness of CASL to probe the collateral circulation.

Dominance of the proximal coordinate frame in determining the locations of hippocampal place cell activity during navigation.

The place-specific activity of hippocampal cells provides downstream structures with information regarding an animal's position within an environment and, perhaps, the location of goals within that environment. In rodents, recent research has suggested that distal cues primarily set the orientation of the spatial representation, whereas the boundaries of the behavioral apparatus determine the locations of place activity. The current study was designed to address possible biases in some previous research that may have minimized the likelihood of observing place activity bound to distal cues. Hippocampal single-unit activity was recorded from six freely moving rats as they were trained to perform a tone-initiated place-preference task on an open-field platform. To investigate whether place activity was bound to the room- or platform-based coordinate frame (or both), the platform was translated within the room at an "early" and at a "late" phase of task acquisition (Shift 1 and Shift 2). At both time points, CA1 and CA3 place cells demonstrated room-associated and/or platform-associated activity, or remapped in response to the platform shift. Shift 1 revealed place activity that reflected an interaction between a dominant platform-based (proximal) coordinate frame and a weaker room-based (distal) frame because many CA1 and CA3 place fields shifted to a location intermediate to the two reference frames. Shift 2 resulted in place activity that became more strongly bound to either the platform- or room-based coordinate frame, suggesting the emergence of two independent spatial frames of reference (with many more cells participating in platform-based than in room-based representations).

Perspectivas filogenéticas del uso de la mano, asimetría cerebral y capacidad de lecto-escritura

Las respuestas que se generan a partir de cuestionamientos del origen del hombre nos permitirán especular hacia dónde evolucionará como especie. Los grandes saltos evolutivos que diferencian a los primates humanos de los no humanos, se podrían describir entre otras características por una eficiente memoria para el uso de herramientas, la dominancia para el uso de la mano junto al desarrollo de la oposición del pulgar y el lenguaje. Se ha descrito un gen, el HSR que expresa para la dominancia para el uso de la mano derecha, habilidades cognitivas relacionadas con el lenguaje y asimetría cerebral en humanos. Este es un gen imprintado, es decir, que se hereda su expresión según el origen parental y cuya expresión está regulada por factores epigenéticos. Estos factores, modifican la expresión del gen sin afectar la estructura primaria del ADN. Se ha estudiado la expresión fenotípica del gen HSR en una población de niños escolarizados de La Rioja, dividida en dos regiones (Región 1 y Región 2). Los resultados obtenidos, que muestran una alteración de las proporciones fenotípicas del gen en la Región 2, apoyan fuertemente la posibilidad de que un factor ambiental estaría condicionando el epigenotipo del gen HSR. Se piensa que el estudio de estos mecanismos regulatorios en estos genes recientemente adquiridos por la evolución y blanco de funciones también recientemente adquiridas, podría dar información de hacia dónde la evolución del hombre podría proyectarse en el futuro.

Robotic Outcome Assessment in a Non-Human Primate Model of Middle Cerebral Artery Stroke

Stroke is a prevalent disorder with immense socioeconomic impact. A variety of chronic neurological deficits result from stroke. In particular, sensorimotor deficits are a significant barrier to achieving post-stroke independence. Unfortunately, the majority of pre-clinical studies that show improved outcomes in animal stroke models have failed in clinical trials. Pre-clinical studies using non-human primate (NHP) stroke models prior to initiating human trials are a potential step to improving translation from animal studies to clinical trials. Robotic assessment tools represent a quantitative, reliable, and reproducible means to assess reaching behaviour following stroke in both humans and NHPs. We investigated the use of robotic technology to assess sensorimotor impairments in NHPs following middle cerebral artery occlusion (MCAO). Two cynomolgus macaques underwent transient MCAO for 90 minutes. Approximately 1.5 years following the procedure these NHPs and two non-stroke control monkeys were trained in a reaching task with both arms in the KINARM exoskeleton. This robot permits elbow and shoulder movements in the horizontal plane. The task required NHPs to make reaching movements from a centrally positioned start target to 1 of 8 peripheral targets uniformly distributed around the first target. We analyzed four movement parameters: reaction time, movement time (MT), initial direction error (IDE), and number of speed maxima to characterize sensorimotor deficiencies. We hypothesized reduced performance in these attributes during a neurobehavioural task with the paretic limb of NHPs following MCAO compared to controls. Reaching movements in the non-affected limbs of control and experimental NHPs showed bell-shaped velocity profiles. In contrast, the reaching movements with the affected limbs were highly variable. We found distinctive patterns in MT, IDE, and number of speed peaks between control and experimental monkeys and between limbs of NHPs with MCAO. NHPs with MCAO demonstrated more speed peaks, longer MTs, and greater IDE in their paretic limb compared to controls. These initial results qualitatively match human stroke subjects’ performance, suggesting that robotic neurobehavioural assessment in NHPs with stroke is feasible and could have translational relevance in subsequent human studies. Further studies will be necessary to replicate and expand on these preliminary findings.

Observação da ação na reabilitação do membro superior de pacientes com acidente vascular cerebral: uma revisão sistemática com metanálise

Background: stroke causes long-term impairments, limitation of activities and restriction in participation in daily life situations, especially for upper limb impairment (UL). Action Observation (AO) has been used for the rehabilitation of UL in these patients. It's a multisensory therapy which consists in observing a healthy subject performing a motor task, followed by physical practice. Objectives: assess whether the AO improves motor function of UL and dependence for activities of daily living (ADLs) of stroke patients or cause any adverse effects. Search methods: a search strategy was words and terms used for the identification of articles, in the following scientific basis Cochrane Central Register of Controlled Trials; MEDLINE; PsycINFO; CINAHL and LILACS. In addition to manual search of the references of articles and search for theses and dissertations in Portal Capes and LILACS. The identification of the studies was conducted from October to December 2015, being the last search on December 3. Selection criteria: randomised controlled trials (RCT) involving adults with stroke who had deficits in upper limb function and used AO as an intervention. Data collection and analysis: the data extracted from the studies were used to analyze the risk of bias, the effect of the treatment and the quality of the body of evidence. Main results: 6 studies were included, totaling 270 patients. The primary outcome analyzed was the motor function of MS. Were combined in meta-analyzes studies comparing AO versus placebo or an active control, considering the immediate and long-term effect (n=241). Regarding the motor function of the arm (5 trials), the estimated effect for the therapy was not significant. However, when considering the hand function estimating the effect was favorable to the group that conducted the AO, in short (mean difference = 6.93, 95% CI 1.48 to 12.39; P = 0.01) and long-term (mean difference = 7.57; 95% CI 1.34 the 13.80; p = 0.02). Unable to perform the analysis for functional dependency. The studies showed a low or uncertain risk of bias, but the quality of evidence the body was considered low and very low quality. Authors’ conclusions: AO was effective in improving hand function of stroke patients. Despite the low quality evidence that the use of OA in clinical practice should not be discouraged. RCT new studies should be conducted with greater methodological rigor and larger samples, covering important outcomes such as functional dependence for ADLs.

Robotic Outcome Assessment in a Non-Human Primate Model of Middle Cerebral Artery Stroke

Stroke is a prevalent disorder with immense socioeconomic impact. A variety of chronic neurological deficits result from stroke. In particular, sensorimotor deficits are a significant barrier to achieving post-stroke independence. Unfortunately, the majority of pre-clinical studies that show improved outcomes in animal stroke models have failed in clinical trials. Pre-clinical studies using non-human primate (NHP) stroke models prior to initiating human trials are a potential step to improving translation from animal studies to clinical trials. Robotic assessment tools represent a quantitative, reliable, and reproducible means to assess reaching behaviour following stroke in both humans and NHPs. We investigated the use of robotic technology to assess sensorimotor impairments in NHPs following middle cerebral artery occlusion (MCAO). Two cynomolgus macaques underwent transient MCAO for 90 minutes. Approximately 1.5 years following the procedure these NHPs and two non-stroke control monkeys were trained in a reaching task with both arms in the KINARM exoskeleton. This robot permits elbow and shoulder movements in the horizontal plane. The task required NHPs to make reaching movements from a centrally positioned start target to 1 of 8 peripheral targets uniformly distributed around the first target. We analyzed four movement parameters: reaction time, movement time (MT), initial direction error (IDE), and number of speed maxima to characterize sensorimotor deficiencies. We hypothesized reduced performance in these attributes during a neurobehavioural task with the paretic limb of NHPs following MCAO compared to controls. Reaching movements in the non-affected limbs of control and experimental NHPs showed bell-shaped velocity profiles. In contrast, the reaching movements with the affected limbs were highly variable. We found distinctive patterns in MT, IDE, and number of speed peaks between control and experimental monkeys and between limbs of NHPs with MCAO. NHPs with MCAO demonstrated more speed peaks, longer MTs, and greater IDE in their paretic limb compared to controls. These initial results qualitatively match human stroke subjects’ performance, suggesting that robotic neurobehavioural assessment in NHPs with stroke is feasible and could have translational relevance in subsequent human studies. Further studies will be necessary to replicate and expand on these preliminary findings.

La compétence sociale des enfants et des adolescents atteints de déficience motrice cérébrale

Les enfants atteints de déficience motrice cérébrale (DMC) intégrés en milieu scolaire ordinaire vivent davantage de difficultés relatives à la compétence sociale que les autres enfants. En lien avec le modèle SOCIAL de Beauchamp et Anderson (2010) (The socio-cognitive integration of abilities model), deux questions sont abordées afin de comprendre ces difficultés. Dans le premier article, les attributions d’intentions (AI) hostiles sont mesurées par le Home Interview with Child (HIWC), un ensemble de vignettes représentants des situations sociales ambigües. Les résultats montrent que l’acceptation sociale, plus que le statut de naissance, est associé à l’hostilité des AI à 15 ans. Les enfants rejetés et populaires ont un niveau d’AI hostiles supérieur aux enfants de la catégorie d’acceptation sociale moyenne. Il est proposé que l’acceptation sociale soit un médiateur important à considérer dans le développement d’un biais d’AI hostile chez les enfants atteints de DMC. Dans le deuxième article, la dominance sociale (i.e., une forme de leadership) est évaluée dans une situation de résolution de problème en équipe. Les comportements relatifs à la dominance sociale (i.e., les comportements prosociaux et coercitifs) sont codifiés à l’aide d’une grille créée et validée pour cette étude. Les résultats révèlent que, sans égard au score d’acceptation sociale, les enfants atteints de DMC effectuent significativement moins de comportements prosociaux et coercitifs que les enfants sans DMC au cours de la résolution de problème. De plus, leur équipe de travail émet un nombre de comportements prosociaux et coercitifs inférieur à celui observé dans l’équipe des deux enfants témoins. Les difficultés de compétence sociale observées chez les jeunes atteints de DMC pourraient être en partie expliquées par une faible dominance sociale lors d’activités sollicitant les fonctions exécutives. Enfin, les deux articles présentés permettent d’explorer de nouvelles avenues pour comprendre et soutenir le développement de la compétence sociale chez les enfants et les adolescents atteints de DMC. Les interventions auprès de cette clientèle devraient avoir lieu tôt et devraient cibler autant les habiletés motrices de ces jeunes que leur compétence sociale, avant que des signaux clairs ne compromettent déjà leur expérience sociale globale en milieu scolaire ordinaire.

Design for placement of modified optodes to non-invasively map cerebral function

By using near infrared spectroscopy (NIRS) and by modifying the current Somanetics® optodes being used with the INVOS oximeter, the modified optodes are made to be fairly functional not only across the forehead, but across the hairy regions of the scalp as well. A major problem arises in the positioning of these optodes on the patients scalp and holding them in place while recording data. Another problem arises in the inconsistent repeatability of the trends displayed in the recorded data. A method was developed to facilitate the easy placement of these optodes on the patients scalp keeping in mind thepatient's comfort. The sensitivity of the optodes, too, was improved by incorporating better refined techniques for manufacturing the fiber optic brushes and fixing the same to the optode transmitting and receiving windows. The modified and improved optodes, in the single as well as in the multiplexed modes, were subjected to various tests on different areas of the brain to determine their efficiency and functionality.

Funtional Near Infrared Spectroscopy Study of Language, Joint Attention and Motor Skills

Near infrared spectroscopy (NIRS) is an emerging non-invasive optical neuro imaging technique that monitors the hemodynamic response to brain activation with ms-scale temporal resolution and sub-cm spatial resolution. The overall goal of my dissertation was to develop and apply NIRS towards investigation of neurological response to language, joint attention and planning and execution of motor skills in healthy adults. Language studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal and fronto-temporal cortex of healthy adults in response to language reception and expression. The mathematical model developed based on granger causality explicated the directional flow of information during the processing of language stimuli by the fronto-temporal cortex. Joint attention and planning/ execution of motor skill studies were performed to investigate the hemodynamic response, synchrony and dominance feature of the frontal cortex of healthy adults and in children (5-8 years old) with autism (for joint attention studies) and individuals with cerebral palsy (for planning/execution of motor skills studies). The joint attention studies on healthy adults showed differences in activation as well as intensity and phase dependent connectivity in the frontal cortex during joint attention in comparison to rest. The joint attention studies on typically developing children showed differences in frontal cortical activation in comparison to that in children with autism. The planning and execution of motor skills studies on healthy adults and individuals with cerebral palsy (CP) showed difference in the frontal cortical dominance, that is, bilateral and ipsilateral dominance, respectively. The planning and execution of motor skills studies also demonstrated the plastic and learning behavior of brain wherein correlation was found between the relative change in total hemoglobin in the frontal cortex and the kinematics of the activity performed by the participants. Thus, during my dissertation the NIRS neuroimaging technique was successfully implemented to investigate the neurological response of language, joint attention and planning and execution of motor skills in healthy adults as well as preliminarily on children with autism and individuals with cerebral palsy. These NIRS studies have long-term potential for the design of early stage interventions in children with autism and customized rehabilitation in individuals with cerebral palsy.

Mapping and modulating spatial attention asymmetries in young and older adults

Healthy young adults demonstrate a group-level, systematic preference for stimuli presented in the left side of space relative to the right (‘pseudoneglect’) (Bowers & Heilman, 1980). This results in an overestimation of features such as size, brightness, numerosity and spatial frequency in the left hemispace, probably as a result of right cerebral hemisphere dominance for visuospatial attention. This spatial attention asymmetry is reduced in the healthy older population, and can be shifted entirely into right hemispace under certain conditions. Although this rightward shift has been consistently documented in behavioural experiments, there is very little neuroimaging evidence to explain this effect at a neuroanatomical level. In this thesis, I used behavioural methodology and electroencephalography (EEG) to map spatial attention asymmetries in young and older adults. I then use transcranial direct current stimulation (tDCS) to modulate these spatial biases, with the aim of assessing age-related differences in response to tDCS. In the first of three experiments presented in this thesis, I report in Chapter Two that five different spatial attention tasks provide consistent intra-task measures of spatial bias in young adults across two testing days. There were, however, no inter-task correlations between the five tasks, indicating that pseudoneglect is at least partially driven by task-dependent patterns of neural activity. In Chapter Three, anodal tDCS was applied separately to the left (P5) and right (P6) posterior parietal cortex (PPC) in young and older adults, with an aim to improve the detection of stimuli appearing in the contralateral visual field. There were no age differences in response to tDCS, but there were significant differences depending on baseline performance. Relative to a sham tDCS protocol, tDCS applied to the right PPC resulted in maintained visual detection across both visual fields in adults who were good at the task at baseline. In contrast, left PPC tDCS resulted in reduced detection sensitivity across both visual fields in poor performers. Finally, in Chapter Four, I report a right-hemisphere lateralisation of EEG activity in young adults that was present for long (but not short) landmark task lines. In contrast, older adults demonstrated no lateralised activity for either line length, thus providing novel evidence of an age-related reduction of hemispheric asymmetry in older adults. The results of this thesis provide evidence of a highly complex set of factors that underlie spatial attention asymmetries in healthy young and older adults.