Nos últimos 20 anos tivemos um grande avanço na neurociência e nas técnicas de avaliação do sistema nervoso em humanos em uma tentativa inicial de compreensão de seu funcionamento. Colaboram com esse avanço técnicas como a eletroencefalografia (EEG), tomografia com-putadorizada (CT), tomografia por emissão de pósitron (PET), ressonância magnética funcional (fMRI), que geram mapas estatísticos de atividade cerebral, e a estimulação magnética transcrania-na (TMS), que se utiliza de pulsos de campo magnético, intensos e rápidos, de forma que a taxa de variação do fluxo magnético possa produzir uma estimulação cortical. No entanto a técnica de TMS ainda hoje utiliza parâmetros subjetivos para a determinação de um centro responsável por uma determinada atividade estimulada, os quais não possibilitam lo-calizar com precisão a região do córtex cerebral que está sendo estimulada por um pulso magnético. No intuito de eliminar essa subjetividade e estimularmos com precisão os centros de ativi-dade esse trabalho realiza um estudo do co-registro das técnicas de TMS e fMRI através de um neu-ronavegador que possibilita encontrar estruturas cerebrais sob uma determinada posição do escalpo. Inicialmente o estimulador foi caracterizado e um mapa de intensidade de campo magnético produ-zido pela bobina em forma de oito ou butterfly foi realizado por diferentes métodos. Em seguida um neuronavegador foi desenvolvido que permite fazer uma superposição das imagens de fMRI com o padrão de campos magnéticos produzido pela bobina. Pode-se variar a posição da bobina e observarem-se as regiões que provavelmente serão estimuladas pelo campo magnético. Com isso pode-se aperfeiçoar a estimulação. Para verificar a eficiência desse método estimulou-se o córtex motor de um grupo de 10 voluntários assintomáticos. O estímulo foi monitorado através de um eletromiógrafo posicionado no músculo abdutor do polegar da mão. Os resultados indicam que com o uso da neuronavegação foi possível estimular a região motora esperada em 100% dos voluntários estudados. / In the last 20 years we witnessed a great advance in neurosciences and evaluation techniques as an initial attempt for understanding of working principles of the human central nervous system Techniques such as electroencephalography (EEG), positron emission tomography (EEG), functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have produced grate advances in the understanding of human cerebral nervous system. fMRI generates statistical maps of the cerebral activity and TMS uses intense and fast magnetic pulses to produce a high rate magnetic flux variation to produce cortical electrical stimulation. However, even today TMS uses subjective parameters to establish an area responsible for a certain stimulated activity, that does not allow the precise cortical localization of the cortex area being stimulated by the magnetic pulse. Aiming to overcome this subjectiveness to more precisely stimulate the activity center this work investigates the use of a co-register method based on TMS and fMRI through the use of a neuronavigator that allows the location of brain structures below a certain scalp position. Initially the TMS was characterized and a map of the magnetic field intensity produced by the eight shaped or butterfly coils was determined by different methods. After this step a neuronavigator was devel-oped allowing a superposition of the magnetic field pattern with the fMRI images. The coil position can be varied and the possible stimulated regions can be visualized. This integration of information is expected to improve the TMS accuracy. To verify the efficacy of this method the motor cortex of 10 asymptomatic volunteers were stimulated. The stimulus was monitored with an electromyogram acquired in the hand thumb abductor muscle. The results shown that with the neuronavigation it was possible to stimulate the desired motor region in all the volunteers studied.

Nos últimos 20 anos tivemos um grande avanço na neurociência e nas técnicas de avaliação do sistema nervoso em humanos em uma tentativa inicial de compreensão de seu funcionamento. Colaboram com esse avanço técnicas como a eletroencefalografia (EEG), tomografia com-putadorizada (CT), tomografia por emissão de pósitron (PET), ressonância magnética funcional (fMRI), que geram mapas estatísticos de atividade cerebral, e a estimulação magnética transcrania-na (TMS), que se utiliza de pulsos de campo magnético, intensos e rápidos, de forma que a taxa de variação do fluxo magnético possa produzir uma estimulação cortical. No entanto a técnica de TMS ainda hoje utiliza parâmetros subjetivos para a determinação de um centro responsável por uma determinada atividade estimulada, os quais não possibilitam lo-calizar com precisão a região do córtex cerebral que está sendo estimulada por um pulso magnético. No intuito de eliminar essa subjetividade e estimularmos com precisão os centros de ativi-dade esse trabalho realiza um estudo do co-registro das técnicas de TMS e fMRI através de um neu-ronavegador que possibilita encontrar estruturas cerebrais sob uma determinada posição do escalpo. Inicialmente o estimulador foi caracterizado e um mapa de intensidade de campo magnético produ-zido pela bobina em forma de oito ou butterfly foi realizado por diferentes métodos. Em seguida um neuronavegador foi desenvolvido que permite fazer uma superposição das imagens de fMRI com o padrão de campos magnéticos produzido pela bobina. Pode-se variar a posição da bobina e observarem-se as regiões que provavelmente serão estimuladas pelo campo magnético. Com isso pode-se aperfeiçoar a estimulação. Para verificar a eficiência desse método estimulou-se o córtex motor de um grupo de 10 voluntários assintomáticos. O estímulo foi monitorado através de um eletromiógrafo posicionado no músculo abdutor do polegar da mão. Os resultados indicam que com o uso da neuronavegação foi possível estimular a região motora esperada em 100% dos voluntários estudados. / In the last 20 years we witnessed a great advance in neurosciences and evaluation techniques as an initial attempt for understanding of working principles of the human central nervous system Techniques such as electroencephalography (EEG), positron emission tomography (EEG), functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have produced grate advances in the understanding of human cerebral nervous system. fMRI generates statistical maps of the cerebral activity and TMS uses intense and fast magnetic pulses to produce a high rate magnetic flux variation to produce cortical electrical stimulation. However, even today TMS uses subjective parameters to establish an area responsible for a certain stimulated activity, that does not allow the precise cortical localization of the cortex area being stimulated by the magnetic pulse. Aiming to overcome this subjectiveness to more precisely stimulate the activity center this work investigates the use of a co-register method based on TMS and fMRI through the use of a neuronavigator that allows the location of brain structures below a certain scalp position. Initially the TMS was characterized and a map of the magnetic field intensity produced by the eight shaped or butterfly coils was determined by different methods. After this step a neuronavigator was devel-oped allowing a superposition of the magnetic field pattern with the fMRI images. The coil position can be varied and the possible stimulated regions can be visualized. This integration of information is expected to improve the TMS accuracy. To verify the efficacy of this method the motor cortex of 10 asymptomatic volunteers were stimulated. The stimulus was monitored with an electromyogram acquired in the hand thumb abductor muscle. The results shown that with the neuronavigation it was possible to stimulate the desired motor region in all the volunteers studied.

Objetivos A estimulação magnética transcraniana (TMS, do inglês: Transcranial Magnetic Stimulation) e as imagens funcionais por ressonância magnética (fMRI, do inglês: functinal Magnetic Resonance Imaging) são duas técnicas não invasivas de investigação de atividade do sistema nervoso central. Porém essas duas técnicas utilizam estratégias diferentes para mensurar a atividade cerebral, sendo que a TMS avalia a resposta elétrica enquanto que a fMRI a resposta hemodinâmica. Nosso intuito nesse trabalho foi criar ferramentas para a comparação dessas duas técnicas no mapeamento do córtex motor, bem como utilizando as ferramentas desenvolvidas, fazer uma comparação dos mapas motores de pacientes com AVC com sujeitos assintomáticos, e nesses dois grupos, também realizar uma avaliação nos efeitos no córtex motor da eletroestimulação sensorial (SES, do inglês: Sensory Electric Stimulation) pelas técnicas de TMS e fMRI. Métodos Paro o mapeamento vetorial do campo magnético produzido pela bobina de TMS utilizamos fantomas que simulavam o tecido cerebral e realizamos medidas de imagens de ressonância magnética (MRI, do inglês: Magnetic Resonance Imaging) de fase em três direções para a construção do mapa vetorial. Uma vez dominada a técnica de mapeamento por imagens de fase, a utilizamos para auxiliar na construção de bobinas para estimulação periférica e pequenos animais. Para realização do mapeamento do córtex motor com TMS desenvolvemos um sistema de neuronavegação (Neuronavegador InVesalius) e um programa para análise dos sinais de eletromiografia (MEPHunter), bem como um segundo programa para fazer o corregistro dos mapas de produzidos pela TMS com os mapas de fMRI (TMSProjection). Em posse dessas ferramentas, pudemos realizar o mapeamento do córtex motor de pacientes com AVCi crônicos. Para tanto estimulamos uma área quadrada de 25cm2 do escalpo sobre o córtex motor e coletamos o potencial evocado nos músculos abdutor curto do polegar ipsi e contralateral à TMS, e nos músculos flexor e extensor radial do carpo, contralaterais à TMS. Para a realização das fMRIs realizamos um paradigma evento-relacionada com um protocolo de abrir e fechar a mão. Por fim avaliamos os efeitos da SES à 3Hz com um única sessão de 30 minutos, realizando medidas de potencial evocado e fMRI imediatamente antes e imediatamente após à SES. Resultados O sistema de neuronavegação juntamente com o conjunto de programas computacionais possibilitou a realização dos estudos clínicos. Nossos dados mostraram uma correlação maior entre os mapas de MEP e os mapas de fMRI nos sujeitos normais do que nos pacientes com AVC, principalmente no hemisfério afetado. Nossos resultados também sugerem que a SES pode provocar modulação na excitabilidade cortical, causando redução da excitabilidade cortical das regiões motoras, quando aplicados na frequência e duração utilizadas nesse estudo. Conclusão O mapeamento de campo magnético por MRI é uma boa alternativa para medir campos complexos e pode ser utilizado no desenvolvimento de novas bobinas de estimulação magética. O neuronavegador Invesalius, o MEPHunter e o TMSProjection são ferramentas poderosas para estudos em neuroimagens podendo ser ampliado seu uso para outras áreas como neurologia e fisioterapia. Quanto aos estudos clínicos acreditamos que o fator que mais colabora para a pior correlação dos mapas dos pacientes é a redução de fibras corticoespinhais e a plasticidade, e que a SES aplicada a 3Hz em uma única sessão tem um efeito agudo de redução da excitabilidade do córtex motor. / Background and Purpose - Transcranial magnetic stimulation (TMS) and functional magnetic resonance images (fMRI) are two noninvasive techniques to investigate the central nervous system activity. These two techniques use different strategies to measure brain activity, once the TMS evaluates the electrical response while the fMRI studies hemodynamic response. Our purpose in this study was to create tools for the comparison of these two techniques for mapping the motor cortex. Latter, using these tools, we compared the motor maps of stroke patients and healthy subjects. Furthermore, we evaluated the effects of electrical stimulation in the sensory motor cortex (SES) by TMS and fMRI techniques. Methods - In order to map the magnetic field vector produced by the TMS coil, we used phantoms that simulated brain tissue and performed measurements of magnetic resonance phase images in three directions, in this way, composing the vector map. Then, we used this technique for helping to build small coils for peripheral and small animals stimulation. For the TMS mapping, we developed a neuronavigation system (InVesalius neuronavigator) and a program to analyze the electromyogram responses (MEPHunter). Secondly, a program to co-register the TMS and fMRI maps (TMSProjection) was created. Using these tools, we mapped the motor cortex of the chronic ischemic stroke patients. For this, we stimulated a square scalp area of 25cm2 over the motor cortex and collected the motor evoked potential (MEP) in the abductor pollicis brevis, ipsilateral and contralateral to TMS, and the flexor and extensor carpi radialis, contralateral to TMS. FMRI was also acquired using an event-related paradigm where the volunteers were asked to open and close their hand. Finally, we evaluated the effects of 3Hz SES in a single 30-minute session, performing measurements of TMS and fMRI before and immediately after the SES. Results - The neuronavigation system and the developed softwares made possible clinical studies. We also found a higher correlation between the MEP and fMRI maps in normal subjects than in stroke patients, especially in the affected hemisphere. Additionally, Our results suggested that SES may cause reduction in cortical excitability of motor regions, when applied with the frequency and duration used in this study. Conclusion - The magnetic field MRI mapping is an efficient alternative for complex fields measuring and can be utilized in the development of new TMS coils geometry. The neuronavigator InVesalius, MEPHunter and TMSProjection are powerful tools for neuroimaging studies and other areas as neurology and physiotherapy. We believe that the most important factor that contributes to the correlation decrease between the MEP and fMRI maps of the patients is the reduction of functional corticospinal fibers and the plasticity of motor areas. In this sense, the 3 Hz SES showed to be a potential technique as therapy in spastic patients.

Objetivos A estimulação magnética transcraniana (TMS, do inglês: Transcranial Magnetic Stimulation) e as imagens funcionais por ressonância magnética (fMRI, do inglês: functinal Magnetic Resonance Imaging) são duas técnicas não invasivas de investigação de atividade do sistema nervoso central. Porém essas duas técnicas utilizam estratégias diferentes para mensurar a atividade cerebral, sendo que a TMS avalia a resposta elétrica enquanto que a fMRI a resposta hemodinâmica. Nosso intuito nesse trabalho foi criar ferramentas para a comparação dessas duas técnicas no mapeamento do córtex motor, bem como utilizando as ferramentas desenvolvidas, fazer uma comparação dos mapas motores de pacientes com AVC com sujeitos assintomáticos, e nesses dois grupos, também realizar uma avaliação nos efeitos no córtex motor da eletroestimulação sensorial (SES, do inglês: Sensory Electric Stimulation) pelas técnicas de TMS e fMRI. Métodos Paro o mapeamento vetorial do campo magnético produzido pela bobina de TMS utilizamos fantomas que simulavam o tecido cerebral e realizamos medidas de imagens de ressonância magnética (MRI, do inglês: Magnetic Resonance Imaging) de fase em três direções para a construção do mapa vetorial. Uma vez dominada a técnica de mapeamento por imagens de fase, a utilizamos para auxiliar na construção de bobinas para estimulação periférica e pequenos animais. Para realização do mapeamento do córtex motor com TMS desenvolvemos um sistema de neuronavegação (Neuronavegador InVesalius) e um programa para análise dos sinais de eletromiografia (MEPHunter), bem como um segundo programa para fazer o corregistro dos mapas de produzidos pela TMS com os mapas de fMRI (TMSProjection). Em posse dessas ferramentas, pudemos realizar o mapeamento do córtex motor de pacientes com AVCi crônicos. Para tanto estimulamos uma área quadrada de 25cm2 do escalpo sobre o córtex motor e coletamos o potencial evocado nos músculos abdutor curto do polegar ipsi e contralateral à TMS, e nos músculos flexor e extensor radial do carpo, contralaterais à TMS. Para a realização das fMRIs realizamos um paradigma evento-relacionada com um protocolo de abrir e fechar a mão. Por fim avaliamos os efeitos da SES à 3Hz com um única sessão de 30 minutos, realizando medidas de potencial evocado e fMRI imediatamente antes e imediatamente após à SES. Resultados O sistema de neuronavegação juntamente com o conjunto de programas computacionais possibilitou a realização dos estudos clínicos. Nossos dados mostraram uma correlação maior entre os mapas de MEP e os mapas de fMRI nos sujeitos normais do que nos pacientes com AVC, principalmente no hemisfério afetado. Nossos resultados também sugerem que a SES pode provocar modulação na excitabilidade cortical, causando redução da excitabilidade cortical das regiões motoras, quando aplicados na frequência e duração utilizadas nesse estudo. Conclusão O mapeamento de campo magnético por MRI é uma boa alternativa para medir campos complexos e pode ser utilizado no desenvolvimento de novas bobinas de estimulação magética. O neuronavegador Invesalius, o MEPHunter e o TMSProjection são ferramentas poderosas para estudos em neuroimagens podendo ser ampliado seu uso para outras áreas como neurologia e fisioterapia. Quanto aos estudos clínicos acreditamos que o fator que mais colabora para a pior correlação dos mapas dos pacientes é a redução de fibras corticoespinhais e a plasticidade, e que a SES aplicada a 3Hz em uma única sessão tem um efeito agudo de redução da excitabilidade do córtex motor. / Background and Purpose - Transcranial magnetic stimulation (TMS) and functional magnetic resonance images (fMRI) are two noninvasive techniques to investigate the central nervous system activity. These two techniques use different strategies to measure brain activity, once the TMS evaluates the electrical response while the fMRI studies hemodynamic response. Our purpose in this study was to create tools for the comparison of these two techniques for mapping the motor cortex. Latter, using these tools, we compared the motor maps of stroke patients and healthy subjects. Furthermore, we evaluated the effects of electrical stimulation in the sensory motor cortex (SES) by TMS and fMRI techniques. Methods - In order to map the magnetic field vector produced by the TMS coil, we used phantoms that simulated brain tissue and performed measurements of magnetic resonance phase images in three directions, in this way, composing the vector map. Then, we used this technique for helping to build small coils for peripheral and small animals stimulation. For the TMS mapping, we developed a neuronavigation system (InVesalius neuronavigator) and a program to analyze the electromyogram responses (MEPHunter). Secondly, a program to co-register the TMS and fMRI maps (TMSProjection) was created. Using these tools, we mapped the motor cortex of the chronic ischemic stroke patients. For this, we stimulated a square scalp area of 25cm2 over the motor cortex and collected the motor evoked potential (MEP) in the abductor pollicis brevis, ipsilateral and contralateral to TMS, and the flexor and extensor carpi radialis, contralateral to TMS. FMRI was also acquired using an event-related paradigm where the volunteers were asked to open and close their hand. Finally, we evaluated the effects of 3Hz SES in a single 30-minute session, performing measurements of TMS and fMRI before and immediately after the SES. Results - The neuronavigation system and the developed softwares made possible clinical studies. We also found a higher correlation between the MEP and fMRI maps in normal subjects than in stroke patients, especially in the affected hemisphere. Additionally, Our results suggested that SES may cause reduction in cortical excitability of motor regions, when applied with the frequency and duration used in this study. Conclusion - The magnetic field MRI mapping is an efficient alternative for complex fields measuring and can be utilized in the development of new TMS coils geometry. The neuronavigator InVesalius, MEPHunter and TMSProjection are powerful tools for neuroimaging studies and other areas as neurology and physiotherapy. We believe that the most important factor that contributes to the correlation decrease between the MEP and fMRI maps of the patients is the reduction of functional corticospinal fibers and the plasticity of motor areas. In this sense, the 3 Hz SES showed to be a potential technique as therapy in spastic patients.

The pathophysiology of psychiatric disorders such as schizophrenia is not fully understood due, in part, to the shortcomings of available neurophysiological techniques. Previous studies have shown that patients with schizophrenia have deficits in dorsolateral prefrontal cortex (DLPFC). In this regard, two major deficits were observed: impairments in gamma-aminobutyric-acid (GABA) neurotransmission and cortical gamma (30-50Hz) oscillations. Previous in vitro and animal studies have linked the modulation of gamma oscillations with GABAB receptor mediated inhibition. Objectives: The first objective was to examine the effect of GABAB receptor mediated inhibition on cortical oscillations in the motor cortex and DLPFC in healthy subjects by using the novel technique of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) and through the TMS paradigm long interval cortical inhibition (LICI), which has been associated with GABAB receptor mediated inhibition. Second, to evaluate the psychometric properties of this neurophysiological paradigm, the validity and reliability of EEG indices of LICI were examined. Finally, the effect of LICI on cortical oscillations was examined in the DLPFC and motor cortex of patients with schizophrenia compared to healthy subjects and patients with bipolar disorder. Hypothesis: It was predicted that EEG measures of LICI would show validity and reliability, and it was hypothesized that patients with schizophrenia would show deficits in inhibition of gamma oscillations in DLPFC compared to healthy subjects and patients with bipolar disorder. Results: The first experiment showed that in healthy subjects LICI inhibited gamma oscillations in the DLPFC but not in the motor cortex. The second experiment demonstrated the validity and reliability of EEG indices of LICI were confirmed in healthy subjects. Finally, patients with schizophrenia had a selective deficit in inhibition of gamma oscillations in the DLPFC which appeared to be independent of illness duration or antipsychotic medication, and it was not observed in bipolar disorder. Conclusions: TMS combined with EEG allows for measuring modulatory effect of LICI on cortical oscillations. Inhibition of gamma oscillations in the DLPFC may be an essential neurophysiological process that may be impaired in schizophrenia. Future studies should ascertain the potential of gamma inhibition deficit as a biological marker for this illness.

The pathophysiology of psychiatric disorders such as schizophrenia is not fully understood due, in part, to the shortcomings of available neurophysiological techniques. Previous studies have shown that patients with schizophrenia have deficits in dorsolateral prefrontal cortex (DLPFC). In this regard, two major deficits were observed: impairments in gamma-aminobutyric-acid (GABA) neurotransmission and cortical gamma (30-50Hz) oscillations. Previous in vitro and animal studies have linked the modulation of gamma oscillations with GABAB receptor mediated inhibition. Objectives: The first objective was to examine the effect of GABAB receptor mediated inhibition on cortical oscillations in the motor cortex and DLPFC in healthy subjects by using the novel technique of transcranial magnetic stimulation (TMS) combined with electroencephalography (EEG) and through the TMS paradigm long interval cortical inhibition (LICI), which has been associated with GABAB receptor mediated inhibition. Second, to evaluate the psychometric properties of this neurophysiological paradigm, the validity and reliability of EEG indices of LICI were examined. Finally, the effect of LICI on cortical oscillations was examined in the DLPFC and motor cortex of patients with schizophrenia compared to healthy subjects and patients with bipolar disorder. Hypothesis: It was predicted that EEG measures of LICI would show validity and reliability, and it was hypothesized that patients with schizophrenia would show deficits in inhibition of gamma oscillations in DLPFC compared to healthy subjects and patients with bipolar disorder. Results: The first experiment showed that in healthy subjects LICI inhibited gamma oscillations in the DLPFC but not in the motor cortex. The second experiment demonstrated the validity and reliability of EEG indices of LICI were confirmed in healthy subjects. Finally, patients with schizophrenia had a selective deficit in inhibition of gamma oscillations in the DLPFC which appeared to be independent of illness duration or antipsychotic medication, and it was not observed in bipolar disorder. Conclusions: TMS combined with EEG allows for measuring modulatory effect of LICI on cortical oscillations. Inhibition of gamma oscillations in the DLPFC may be an essential neurophysiological process that may be impaired in schizophrenia. Future studies should ascertain the potential of gamma inhibition deficit as a biological marker for this illness.

No description available.

This thesis is about what happens in the brain when people switch between tasks. Each task requires a particular assembly of cognitive processes, an orientation of attention and set of rules relating action to input — a "task-set". The research reported used a task-cueing paradigm to study preparatory control of task-set. On each trial a stimulus (a coloured shape) was preceded by a verbal task-cue specifying which task to do (judge the shape or the colour of the stimulus). Reaction time and error rate increase on trials when the task changes relative to trials on which it does not. When the cue stimulus interval (CSI) is increased, this "switch cost" is reduced, indexing a process of task-set reconfiguration in which top-down control is employed to reconfigure the task-set parameters. Effective reconfiguration may also be indicated by a reduction in the "response congruence effect" — poorer performance on stimuli mapped to different responses for the two tasks than for stimuli mapped to the same response. I present six experiments using transcranial magnetic stimulation (TMS), a technique for interfering briefly and harmlessly with neuronal activity in a small region of cortex, to address the question of which brain regions contribute to anticipatory control of task-set as indexed by these behavioural measures. To help guide the selection of candidate brain regions, I first present a review and meta-analysis of neuroimaging studies of task-switching in the literature. Many fMRI studies, comparing brain activation on task-switch and -repeat trials have been published. Some have also tried to isolate activations related specifically to pro-active control of task-set. The activations reported are quite inconsistent over studies. I used a quantitative meta-analysis technique to identify which brain regions are most consistently found by studies reporting switch minus repeat contrasts and which may be specifically important for preparation on switch trials. The experiments examined the effect of stimulating several regions during the long cue-stimulus interval of a task-cueing paradigm, relative to control conditions. A first pair of experiments suggests an important role in proactive task-set control for two regions in dorsal medial frontal cortex, the supplementary motor area (SMA) and an area known as pre-SMA, though the former region appeared to contribute to reducing the switch cost while the latter appeared to reduce the effects of response congruence. In a further three experiments, I examined the role of the right intra-parietal sulcus (rIPS); this appears to play a crucial role in preparation for a task-switch but not post-stimulus task-set reconfiguration. In a final experiment, I used TMS guided by fMRI activations in the same participants to study the effects of stimulation over the left inferior frontal junction (IFJ). The results indicate that a region just anterior to the left IFJ is specifically important for preparing for a switch trial. I discuss the roles that may be played by these three regions in task-set control.

The neural correlates that underpin fine motor control of the hand and their connections with the primary motor cortex (M1) require further investigation. Brodmann’s area 5 located in the superior parietal lobule (SPL) is suggested to be an important cortical area involved in the processing of somatosensory input important for precision movements. Area 5 is present in monkey species capable of opposable thumb movements and it is proposed that this area evolved with the ability to execute manual behaviours such as pinch grip. Further, area 5 is dominated by the representation of the hand and forelimb, and has direct connectivity with M1 implicating its role in the control of hand movements. Few studies have investigated the function of area 5 in humans and none have examined the connectivity between area 5 and ipsilateral M1. This thesis presents a novel approach to study the influence of area 5 on M1 output in healthy and awake humans during the processing of somatosensory inputs and during performance of motor tasks involving the hand. Using paired pulse transcranial magnetic stimulation over left area 5 and ipsilateral M1, the connections between the two cortical loci was probed. It was hypothesized that area 5 would facilitate M1 output at short and long latencies during the processing of tactile inputs and during the performance of motor tasks compared to rest. The current results demonstrate that changes in M1 output are task and temporally specific. Facilitation of the motor evoked potential (MEP) was present at short latency of 6 ms during the processing of somatosensory input whereas inhibition was present during conditions where the hand was performing a task with the thumb and index finger. Further, an inhibitory effect was seen at 40 ms during cutaneous stimulation. In experiments 1 and 2, there was no net influence of area 5 on M1 output observed at rest. The findings presented may have revealed a novel path with which to alter the motor output, and possibly movement of hand muscles.

The neural correlates that underpin fine motor control of the hand and their connections with the primary motor cortex (M1) require further investigation. Brodmann’s area 5 located in the superior parietal lobule (SPL) is suggested to be an important cortical area involved in the processing of somatosensory input important for precision movements. Area 5 is present in monkey species capable of opposable thumb movements and it is proposed that this area evolved with the ability to execute manual behaviours such as pinch grip. Further, area 5 is dominated by the representation of the hand and forelimb, and has direct connectivity with M1 implicating its role in the control of hand movements. Few studies have investigated the function of area 5 in humans and none have examined the connectivity between area 5 and ipsilateral M1. This thesis presents a novel approach to study the influence of area 5 on M1 output in healthy and awake humans during the processing of somatosensory inputs and during performance of motor tasks involving the hand. Using paired pulse transcranial magnetic stimulation over left area 5 and ipsilateral M1, the connections between the two cortical loci was probed. It was hypothesized that area 5 would facilitate M1 output at short and long latencies during the processing of tactile inputs and during the performance of motor tasks compared to rest. The current results demonstrate that changes in M1 output are task and temporally specific. Facilitation of the motor evoked potential (MEP) was present at short latency of 6 ms during the processing of somatosensory input whereas inhibition was present during conditions where the hand was performing a task with the thumb and index finger. Further, an inhibitory effect was seen at 40 ms during cutaneous stimulation. In experiments 1 and 2, there was no net influence of area 5 on M1 output observed at rest. The findings presented may have revealed a novel path with which to alter the motor output, and possibly movement of hand muscles.