Damage to motor areas of the brain, caused by stroke, can produce devastating motor deficits, including aberrant control of force. After stroke, reorganization of the brain’s motor system has been identified as one of the fundamental mechanisms involved in recovery of motor control after stroke. Yet, few studies have investigated how force production and modulation are encoded in the brain after stroke and how this relates to motor outcome. Thus, the purpose of this study was to (1) understand how past neuroimaging literature has contributed to establishing common patterns of brain reorganization during both relative and absolute force production after stroke, (2) examine how brain function is reorganized during force production and modulation in individuals with stroke, and (3) relate this task-related reorganization of brain function to the amount of paretic arm use after stroke. In the second chapter, we systematically reviewed all relevant literature examining brain activation during force production after stroke. The following chapters (chapters 3 and 4) applied functional magnetic resonance imaging (fMRI) to examine the neural correlates of force production and modulation after stroke. Chapter 2 supports differences in task-related brain activation dependent on features of stroke, such as severity and chronicity, as well as influence of rehabilitation. In addition, results suggest that activation of common motor areas of the brain during force production can be identified in relation to functional outcome after stroke. Results from the subsequent two chapters (3 and 4), demonstrate that brain function reorganizes in terms of absolute, and not relative force production after stroke. Specifically, stroke participants exhibit greater activation of motor areas than healthy controls when matched for absolute force production. Moreover, there is a relationship between paretic arm usage and brain activation, where stroke participants having less paretic arm use, as measured using wrist accelerometers, exhibit higher brain activation. Results of this thesis suggest that during absolute force production, brain activation may approach near maximal levels in stroke participants at lower forces than healthy controls. Furthermore, this effect may be amplified even further in subjects with less paretic arm usage, as increased activation in motor areas occurs in participants with less arm use after stroke. Ultimately, the results from this thesis will contribute to research relevant to brain reorganization in individuals with stroke and may lead to the development of new, beneficial therapeutic interventions that optimize brain reorganization and improve functional recovery after stroke.

Damage to motor areas of the brain, caused by stroke, can produce devastating motor deficits, including aberrant control of force. After stroke, reorganization of the brain’s motor system has been identified as one of the fundamental mechanisms involved in recovery of motor control after stroke. Yet, few studies have investigated how force production and modulation are encoded in the brain after stroke and how this relates to motor outcome. Thus, the purpose of this study was to (1) understand how past neuroimaging literature has contributed to establishing common patterns of brain reorganization during both relative and absolute force production after stroke, (2) examine how brain function is reorganized during force production and modulation in individuals with stroke, and (3) relate this task-related reorganization of brain function to the amount of paretic arm use after stroke. In the second chapter, we systematically reviewed all relevant literature examining brain activation during force production after stroke. The following chapters (chapters 3 and 4) applied functional magnetic resonance imaging (fMRI) to examine the neural correlates of force production and modulation after stroke. Chapter 2 supports differences in task-related brain activation dependent on features of stroke, such as severity and chronicity, as well as influence of rehabilitation. In addition, results suggest that activation of common motor areas of the brain during force production can be identified in relation to functional outcome after stroke. Results from the subsequent two chapters (3 and 4), demonstrate that brain function reorganizes in terms of absolute, and not relative force production after stroke. Specifically, stroke participants exhibit greater activation of motor areas than healthy controls when matched for absolute force production. Moreover, there is a relationship between paretic arm usage and brain activation, where stroke participants having less paretic arm use, as measured using wrist accelerometers, exhibit higher brain activation. Results of this thesis suggest that during absolute force production, brain activation may approach near maximal levels in stroke participants at lower forces than healthy controls. Furthermore, this effect may be amplified even further in subjects with less paretic arm usage, as increased activation in motor areas occurs in participants with less arm use after stroke. Ultimately, the results from this thesis will contribute to research relevant to brain reorganization in individuals with stroke and may lead to the development of new, beneficial therapeutic interventions that optimize brain reorganization and improve functional recovery after stroke.

This report extends findings (Duffy & Mitchell, 2013) of a dramatic recovery of vision in the deprived eye of amblyopic kittens following a short ‘dark-pulse’ (a 10 day period of darkness) to situations of clinical relevance. To this end, the initial deprivation began at post-natal day 7 rather than post-natal day 30. As before, the dark-pulse was imposed either immediately after the initial monocular deprivation, or was delayed several weeks after stable amblyopia was establsihed. In some animals, this dark-pulse was shortened, or disrupted by short periods of daily binocular visual experience. The effects on the visual acuity and alignment acuity of the two eyes were documented as well as the effects on binocular depth perception. The benefits of a short dark-pulse were identical to those of the prior study. A dark-pulse of 5 days was ineffective as was a dark-pulse interrupted daily by light for 30-minutes.

Damage to motor areas of the brain, caused by stroke, can produce devastating motor deficits, including aberrant control of force. After stroke, reorganization of the brain’s motor system has been identified as one of the fundamental mechanisms involved in recovery of motor control after stroke. Yet, few studies have investigated how force production and modulation are encoded in the brain after stroke and how this relates to motor outcome. Thus, the purpose of this study was to (1) understand how past neuroimaging literature has contributed to establishing common patterns of brain reorganization during both relative and absolute force production after stroke, (2) examine how brain function is reorganized during force production and modulation in individuals with stroke, and (3) relate this task-related reorganization of brain function to the amount of paretic arm use after stroke. In the second chapter, we systematically reviewed all relevant literature examining brain activation during force production after stroke. The following chapters (chapters 3 and 4) applied functional magnetic resonance imaging (fMRI) to examine the neural correlates of force production and modulation after stroke. Chapter 2 supports differences in task-related brain activation dependent on features of stroke, such as severity and chronicity, as well as influence of rehabilitation. In addition, results suggest that activation of common motor areas of the brain during force production can be identified in relation to functional outcome after stroke. Results from the subsequent two chapters (3 and 4), demonstrate that brain function reorganizes in terms of absolute, and not relative force production after stroke. Specifically, stroke participants exhibit greater activation of motor areas than healthy controls when matched for absolute force production. Moreover, there is a relationship between paretic arm usage and brain activation, where stroke participants having less paretic arm use, as measured using wrist accelerometers, exhibit higher brain activation. Results of this thesis suggest that during absolute force production, brain activation may approach near maximal levels in stroke participants at lower forces than healthy controls. Furthermore, this effect may be amplified even further in subjects with less paretic arm usage, as increased activation in motor areas occurs in participants with less arm use after stroke. Ultimately, the results from this thesis will contribute to research relevant to brain reorganization in individuals with stroke and may lead to the development of new, beneficial therapeutic interventions that optimize brain reorganization and improve functional recovery after stroke. / Medicine, Faculty of / Graduate

ABSTRACT In the context of increasing incidence of stroke (but also an increasing rate of survival), non-invasive brain stimulation techniques (NIBS) are more frequently used for patients with post-stroke aphasia (PWA) and post-stroke depression (PSD). NIBS techniques, modulating brain plasticity, might offer valid, alternative therapeutic strategies. The aim is to reach a better outcome because treatment of aphasia can also improve post-stroke depression and vice versa. Based on two literature reviews on NIBS effects on PSD and post-stroke aphasia the conclusion is that, although the field is relatively new, and many more investigations with larger samples of patients are required, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) clinical application is well tolerated, safe, and feasible. Starting from these encouraging data, we used a combination of TMS and electroencephalography (EEG) to explore the excitability modulation before and after active (20 sessions) and sham (20 sessions) tDCS in a double-blind crossover experiment. Four chronic non fluent PWA underwent 8 weeks of verbal exercises coupled with tDCS over the perilesional areas close to the left inferior frontal gyrus. To evaluate changes induced by tDCS, TMS-EEG responses over Brodmann area 6 (BA6) were computed using five different parameters. In addition, these data were compared with those recorded from a matched control group. The results indicated a slight improvement after tDCS stimulation (as compared to sham) for patients with Broca’s aphasia, but not for those with global aphasia. Also, TMS-evoked EEG responses recorded from the ipsilesional hemisphere were abnormal in individuals with chronic post-stroke aphasia (slower and simple responses with higher amplitudes) when compared to responses from the contralesional hemisphere and from the control group. Critically, the Global Mean Field Power (GMFP), Local Mean Field Power (LMFP) and Natural Frequency values were modulated by anodal tDCS. Despite these interesting results, further data are needed in order the obtain more direct, stronger evidence linking behavioral tDCS effects and neurophysiological data.

New neuroimaging techniques have made it possible to examine imagery and found evidence for that imagery share similar neural correlates as in perception. Imagery can be used in different areas to enhance performance, and it is a popular technique in sports. Similar to physical practice (PP), motor imagery (MI) can result in brain plasticity. The aim of this thesis is to describe what imagery means and describe different theories of imagery. This is to further look into what impact MI has on performance in different sports, and then to further see if there are any changes in brain plasticity as a result of using MI. There is a lack of studies done on MI, performance and brain plasticity in sport. To answer the latter focus of this thesis, studies of healthy persons and patient studies using MI to improve performance and examining changes in the brain have been used. In order to do that this thesis aims to do a literature review. The results indicate that MI combined with PP can improve sport performance. It has also been showed that MI alone can be as good as PP. Most studies found that MI combined with PP can result in brain plasticity, and only one study did not found evidence for it. It has also showed that MI alone can result in brain plasticity. Future research should include larger samples, matching subjects, and comparing the effects of MI in several kinds of sports.

As opposed to earlier beliefs, the brain is altering itself throughout an individual’s life. The process of functional or structural alterations is referred to as plasticity, and can be induced by several factors such as experience or physical exercise. In this thesis, the research area of experience-dependent plasticity, with focus on exercise-induced plasticity is examined critically. Evidence from a vast array of studies are reviewed and compared in order to find whether physical exercise can induce neural plasticity in the human brain, how it may be beneficial, and what some of the plausible mediators of exercise-induced plasticity are. The findings demonstrated in this thesis suggest that although there are knowledge gaps and limitations in the literature, physical exercise can indeed result in exhibited plasticity as well as being beneficial for the human brain in several ways.

Partial paralysis of the hand is one of the main impairments after stroke. Constraint Induced Movement Therapy (CIT) is a new treatment technique that appears to improve upper extremity function after stroke. CIT consists of 6 hours of training/day for the affected arm (mainly with shaping exercises) and of restraint (mitt) of the non affected arm for two weeks. There are concerns about the practicality and resource issues in carrying out CIT according to the original model. In this thesis the benefit of modifications of CIT, of an assessment tool and of two common types of hand training have been evaluated.   CIT (n=16) administered in groups for two weeks (paper I) seems to be a feasible alternative to improve upper limb motor function after chronic stroke. The arm/hand motor performance improved significantly on Motor Assessment Scale (MAS; p= 0.003) and on Sollerman hand function test (p= 0.037). The median self reported motor ability (MAL) also improved (p < 0.001). No additional effect was seen from wearing a mitt for an extended period of three months. The reliability of the Sollerman hand function test (paper II) was studied in patients with chronic stroke. Three examiners observed 24 patients at three experimental sessions. There was agreement (kappa ≥ 0.4) between the examiners for 15/20 subtests. Using total sum scores, the agreement within the examiners was higher than 0.96 (for Spearman’s rhos and ICCs) and agreement between the examiners was higher than 0.96 (Spearman’s rhos) and 0.92 (ICCs), respectively. In a cohort of 24 patients with subacute stroke (paper III) forced use therapy (FUT; mitt use and 3 hours of training/day for 2 weeks) improved arm/hand function, but not more than regular arm therapy given to the control group. Significant improvements in arm/hand motor performance were found in the FUT group (n=12) as well as in the control group (n=12) on the Sollerman hand function test (p= 0.001), on MAS (p< 0.05) and on MAL (p < 0.05). No significant differences were seen between the groups pre- or post training or at three months follow up, demonstrating that the mitt had limited importance. In a separate study on 30 healthy subjects (paper IV), employing transcranial magnetic brain stimulation (TMS), we found that shaping exercises but not general activity training increased dexterity (p<0.05; Purdue peg board test) of the trained non dominant hand. After shaping exercises the cortical motor map shifted forwardly into the premotor area but did not expand. After general activity training the cortical motor map expanded significantly (p=0.03) in the posterior (sensory) direction. Shift of location of active TMS positions rather than their numbers might therefore be a critical factor for the interpretation of cortical plasticity.   In conclusion, the studies in this thesis have shown that less resource consuming modifications of CIT may be feasible to improve upper limb motor function after stroke. The type and amount of training for the more affected arm seems to be an important factor rather than the mitt use in itself. Shaping exercises, at least in healthy people, are effective in improving dexterity and the Sollerman hand function test reliable to evaluate arm/hand function after stroke.

O declínio das capacidades motoras é inevitável ao longo do envelhecimento, porém, a curva desse declínio pode ser reduzida quando o exercício físico é utilizado como forma de intervenção. Em geral, envolvem a repetição de movimentos cíclicos e de baixa complexidade, com o objetivo de aumentar a eficiência fisiológica dos praticantes. Entretanto, há evidências que comprovam a plasticidade cerebral de animais, inclusive em animais idosos, que foram expostos a ambientes e experiências enriquecedoras. Estudos com humanos permitiram observar que os efeitos da aprendizagem de habilidades motoras estão associados a mudanças não apenas comportamentais, mas também nas estruturas cerebrais. Os resultados desses estudos têm sido discutidos em termos do esforço cognitivo relativo ao processo de aprendizagem e, em especial, das habilidades motoras complexas. Neste sentido, este estudo pretendeu verificar os efeitos de dois programas de exercícios físicos nas estruturas cerebrais e capacidades motoras de idosas. Mais especificamente, em uma situação experimental de ensino, foram aplicados dois programas de exercícios físicos, um voltado para a prática de habilidades motoras complexas e o outro voltado especificamente para a prática de movimentos de baixa complexidade (simples). Foram avaliados os efeitos desses programas sobre as estruturas cerebrais, por meio de ressonância magnética cerebral e, também, sobre as capacidades motoras, por meio de testes de capacidade funcional. Participaram do estudo 40 mulheres com idade média de 66,56 anos. Foram formados 3 grupos: Condicionamento Físico, Jogos e Controle. O programa de exercícios teve a duração de 14 semanas, com 3 sessões semanais. As avaliações ocorreram no início e no final dos programas nos 3 grupos. Os resultados revelaram que o grupo controle não apresentou mudanças significantes nas capacidades motoras nem em relação às estruturas cerebrais. O grupo Condicionamento Físico obteve melhora significante no desempenho dos testes de força de membros superiores, flexibilidade de membros inferiores e agilidade/equilíbrio dinâmico. Já o grupo Jogos demonstrou aumento significante no desempenho dos testes de flexibilidade de membros inferiores, agilidade/equilíbrio dinâmico e equilíbrio pé direito olho aberto. Entretanto, nenhum dos grupos, inclusive daqueles que praticaram exercícios físicos, apresentou mudanças significantes no que diz respeito às estruturas cerebrais. Concluiu-se que os programas de exercícios físicos foram parcialmente efetivos para a melhora das capacidades motoras, mas não promoveram alterações na estrutura cerebral / Although the diminishing in the motor abilities is inevitable along the aging process, the tendency of this decrease may be reduced when physical exercise is used as an intervention. These interventions, in general, include the repetition of movements which are cyclical and have low complexity, aiming to increase physiological efficiency of the practitioners. There are evidences of animal\'s brain plasticity, including elderly animals, which have been exposed to enriching environments and experiences. Studies with human beings have lead to the conclusion that the motor learning effects are associated to changes not only behavioral, but also in brain structure. The results of these studies have been discussed in terms of the cognitive effort related to the learning process and, specially, to the complex motor skills. Therefore this study aimed to verify the effects of two programs of physical exercises on the brain structure and motor capacities of elderly women. Specifically, in an experimental teaching condition, there have been developed two physical exercises programs: one oriented to the practice of complex motor skills; and the other directed to the practice of low complexity movements (simple). The effects of these programs in the brain structure have been evaluated through cerebral magnetic resonance and, also, in the motor capacities through functional capacities tests. Forty women with mean age of 66.56 years old have taken part of the study. There were three groups: Fitness, Games and Control. The exercises programs were developed during 14 weeks, with 3 sessions per week. The evaluations were in the beginning and in the end of the program. Results showed that the Control group has neither presented changes in their motor capacities nor related to their brain structures. The Fitness group significantly improved its performance in the tests for upper body strength, flexibility of the limbs and agility/ dynamic balance. The Games group demonstrated significant increase in the test for flexibility of the limbs, agility/dynamic balance and balance right foot open eye. Even though, none of the groups, including those which have practiced physical exercises, presented changes in their brain structures. In conclusion, the physical exercise programs have been partially effective for the improvement of the motor capacities, but have not brought changes in the brain structure

O declínio das capacidades motoras é inevitável ao longo do envelhecimento, porém, a curva desse declínio pode ser reduzida quando o exercício físico é utilizado como forma de intervenção. Em geral, envolvem a repetição de movimentos cíclicos e de baixa complexidade, com o objetivo de aumentar a eficiência fisiológica dos praticantes. Entretanto, há evidências que comprovam a plasticidade cerebral de animais, inclusive em animais idosos, que foram expostos a ambientes e experiências enriquecedoras. Estudos com humanos permitiram observar que os efeitos da aprendizagem de habilidades motoras estão associados a mudanças não apenas comportamentais, mas também nas estruturas cerebrais. Os resultados desses estudos têm sido discutidos em termos do esforço cognitivo relativo ao processo de aprendizagem e, em especial, das habilidades motoras complexas. Neste sentido, este estudo pretendeu verificar os efeitos de dois programas de exercícios físicos nas estruturas cerebrais e capacidades motoras de idosas. Mais especificamente, em uma situação experimental de ensino, foram aplicados dois programas de exercícios físicos, um voltado para a prática de habilidades motoras complexas e o outro voltado especificamente para a prática de movimentos de baixa complexidade (simples). Foram avaliados os efeitos desses programas sobre as estruturas cerebrais, por meio de ressonância magnética cerebral e, também, sobre as capacidades motoras, por meio de testes de capacidade funcional. Participaram do estudo 40 mulheres com idade média de 66,56 anos. Foram formados 3 grupos: Condicionamento Físico, Jogos e Controle. O programa de exercícios teve a duração de 14 semanas, com 3 sessões semanais. As avaliações ocorreram no início e no final dos programas nos 3 grupos. Os resultados revelaram que o grupo controle não apresentou mudanças significantes nas capacidades motoras nem em relação às estruturas cerebrais. O grupo Condicionamento Físico obteve melhora significante no desempenho dos testes de força de membros superiores, flexibilidade de membros inferiores e agilidade/equilíbrio dinâmico. Já o grupo Jogos demonstrou aumento significante no desempenho dos testes de flexibilidade de membros inferiores, agilidade/equilíbrio dinâmico e equilíbrio pé direito olho aberto. Entretanto, nenhum dos grupos, inclusive daqueles que praticaram exercícios físicos, apresentou mudanças significantes no que diz respeito às estruturas cerebrais. Concluiu-se que os programas de exercícios físicos foram parcialmente efetivos para a melhora das capacidades motoras, mas não promoveram alterações na estrutura cerebral / Although the diminishing in the motor abilities is inevitable along the aging process, the tendency of this decrease may be reduced when physical exercise is used as an intervention. These interventions, in general, include the repetition of movements which are cyclical and have low complexity, aiming to increase physiological efficiency of the practitioners. There are evidences of animal\'s brain plasticity, including elderly animals, which have been exposed to enriching environments and experiences. Studies with human beings have lead to the conclusion that the motor learning effects are associated to changes not only behavioral, but also in brain structure. The results of these studies have been discussed in terms of the cognitive effort related to the learning process and, specially, to the complex motor skills. Therefore this study aimed to verify the effects of two programs of physical exercises on the brain structure and motor capacities of elderly women. Specifically, in an experimental teaching condition, there have been developed two physical exercises programs: one oriented to the practice of complex motor skills; and the other directed to the practice of low complexity movements (simple). The effects of these programs in the brain structure have been evaluated through cerebral magnetic resonance and, also, in the motor capacities through functional capacities tests. Forty women with mean age of 66.56 years old have taken part of the study. There were three groups: Fitness, Games and Control. The exercises programs were developed during 14 weeks, with 3 sessions per week. The evaluations were in the beginning and in the end of the program. Results showed that the Control group has neither presented changes in their motor capacities nor related to their brain structures. The Fitness group significantly improved its performance in the tests for upper body strength, flexibility of the limbs and agility/ dynamic balance. The Games group demonstrated significant increase in the test for flexibility of the limbs, agility/dynamic balance and balance right foot open eye. Even though, none of the groups, including those which have practiced physical exercises, presented changes in their brain structures. In conclusion, the physical exercise programs have been partially effective for the improvement of the motor capacities, but have not brought changes in the brain structure