In imaging, short wavelength (high-frequency) particles scattered from targets typically yield greater spatial resolutions than longer wavelengths. X-Rays, for example are typically within 2 orders of magnitude of a nanometer wavelength to achieve desired resolutions for medical imaging. Although better for imaging, this poses a health risk for subjects as ionizing radiation and this limits its use. Functional Magnetic Resonance Imaging (fMRI) avoids this issue by using radiation of much larger wavelengths, 4.8 m (62.5 MHz), that are relatively harmless. Instead of scattering, these photons are used to excite protons between spin-states in an external magnetic field. Magnetization relaxation rates and dephasing as a function of space and time are then measured to reconstruct images. This dissertation develops experimental methods to understand and interpret the biophysical underpinnings of fMRI in terms of blood flow and oxygen concentration changes. In neuroscience, fMRI may be used to deduce brain activity. Brain activity is a general term related to neuronal firing rate, which metabolizes oxygen. Deoxygenated blood increases proton spin dephasing. This is the physical mechanism that ultimately yields contrast in the fMRI signal. This is known as Blood-Oxygen Level Dependent (BOLD) contrast. A critical piece of information in this process, hemodynamics, is the dynamics of cerebral (brain) oxygen concentrations in relation to blood flow. The hemodynamics of BOLD contrast fMRI and its relation to brain activity is vital. In this dissertation, I have classified hemodynamic data as a function of space and time in cerebral cortex as well as testing a rudimentary hemodynamic model. I have taken fMRI measurements in three human subjects to identify spatial and temporal hemodynamic trends in brain. Furthermore, I've analyzed laser-speckle imaging in three subjects to identify spatiotemporal trends in blood speed. The final portion of this dissertation relates developments of a hemodynamic model of BOLD. / text

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.

O mecanismo de contraste mais utilizado em imagens funcionais por ressonância magnética (functional Magnetic Resonance Imaging, fMRI), também conhecido por sinal BOLD (Blood Oxygenation Level Dependent) mede indiretamente a atividade neural, sendo sensível a mudanças no fluxo cerebral sangüíneo (Cerebral Blood Flow, CBF), na taxa cerebral metabólica do oxigênio (Cerebral Metabolic Rate of Oxygen, CMRO2) e no volume cerebral sanguíneo (Cerebral Blood Volume, CBV) e, em princípio, ele pode ser utilizado para mapear perfusão cerebral. Desse modo, o objetivo principal deste trabalho foi investigar, quantitativamente, alterações perfusionais no cérebro humano mapeadas pelas mudanças do sinal BOLD em resposta à indução transitória do estado de apnéia. Para isso, imagens por ressonância magnética foram obtidas através de um scanner de 1.5 T Siemens (Magneton Vision) com seqüências do tipo EPI-BOLD. Nesta pesquisa, foi analisada a influência da duração da apnéia no sinal BOLD. Observou-se, também, a diferença ocasionada no sinal em duas situações: apnéia iniciando-se após a inspiração ou após a expiração. Além disso, foi estudada a propagação deste sinal BOLD pelas diferentes regiões cerebrais. Por último, fazendo uso deste sinal BOLD, construiu-se mapas para obter informações a respeito do volume cerebral sangüíneo. Pelos dados obtidos, foi possível analisar o comportamento do sinal BOLD quando na presença de diferentes PaO2 e PaCO2. Observaram-se, também, diferenças regionais na sensibilidade do sinal BOLD ocasionada pelo estado de apnéia induzido. Essa diferença pode estar relacionada à reatividade das artérias que irrigam cada região ou ao volume sangüíneo basal dessas artérias. Além disso, foi possível obter informações a respeito das características temporais da mudança do CBF para diferentes regiões do cérebro em resposta a hipercapnia. Também, foi feita a identificação de áreas corticais responsáveis pelo controle voluntário da respiração. Por fim, os mapas de B-CBV obtidos utilizando o contraste BOLD em resposta à apnéia foram capazes de refletir o volume sangüíneo local, embora, estudos para análise dos outros parâmetros que influenciam o sinal devam ser realizados. / The BOLD (Blood Oxygenation Level Dependent) signal, is the most used contrast mechanism of the so called functional Magnetic Resonance Imaging (fMRI). Although it indirectly measures neuronal activity, its response is directly related to cerebral blood flow (CBF), Cerebral Metabolic Rate of Oxygen (CMRO2) and Cerebral Blood Volume (CBV) and can be, in principle, used to map cerebral perfusion. Thus, the main purpose of this study was to investigate, quantitatively, some aspects of perfusional alterations in the human brain. These changes were mapped by changes in the BOLD signal as a result of a global and uniform stimulation: hypercapnia induced by breath holding paradigms. Magnetic resonance images were acquired in a 1.5 T scanner (Siemens, Magneton Vision) with EPI-BOLD fMRI sequences. It was analyzed the BOLD dependency on breath holding duration and differences on the BOLD signal due the employed breath holding techniques: breath holding after expiration or after inspiration. The regional variability of the BOLD signal propagation was also studied. Moreover, the signal was used to construct maps based on CBV information. It was possible to gain information about the BOLD signal behavior that respond to PaO2 and PaCO2 alterations. Besides, it was demonstrated its regional variations sensibility, which can be correlated with arterial reactivity or the rest CBV of this arteries. It was also possible acquire information about the temporal characteristics of CBF changes induced by hypercapnia across brain regions as well as the identification of cortical areas that were responsible to the voluntary breathing. Finally, the B-CBV maps that used the BOLD con-trast were able to reflect CBV information, although, it is necessary the study of other parameters that can influence the signal.

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.

O mecanismo de contraste mais utilizado em imagens funcionais por ressonância magnética (functional Magnetic Resonance Imaging, fMRI), também conhecido por sinal BOLD (Blood Oxygenation Level Dependent) mede indiretamente a atividade neural, sendo sensível a mudanças no fluxo cerebral sangüíneo (Cerebral Blood Flow, CBF), na taxa cerebral metabólica do oxigênio (Cerebral Metabolic Rate of Oxygen, CMRO2) e no volume cerebral sanguíneo (Cerebral Blood Volume, CBV) e, em princípio, ele pode ser utilizado para mapear perfusão cerebral. Desse modo, o objetivo principal deste trabalho foi investigar, quantitativamente, alterações perfusionais no cérebro humano mapeadas pelas mudanças do sinal BOLD em resposta à indução transitória do estado de apnéia. Para isso, imagens por ressonância magnética foram obtidas através de um scanner de 1.5 T Siemens (Magneton Vision) com seqüências do tipo EPI-BOLD. Nesta pesquisa, foi analisada a influência da duração da apnéia no sinal BOLD. Observou-se, também, a diferença ocasionada no sinal em duas situações: apnéia iniciando-se após a inspiração ou após a expiração. Além disso, foi estudada a propagação deste sinal BOLD pelas diferentes regiões cerebrais. Por último, fazendo uso deste sinal BOLD, construiu-se mapas para obter informações a respeito do volume cerebral sangüíneo. Pelos dados obtidos, foi possível analisar o comportamento do sinal BOLD quando na presença de diferentes PaO2 e PaCO2. Observaram-se, também, diferenças regionais na sensibilidade do sinal BOLD ocasionada pelo estado de apnéia induzido. Essa diferença pode estar relacionada à reatividade das artérias que irrigam cada região ou ao volume sangüíneo basal dessas artérias. Além disso, foi possível obter informações a respeito das características temporais da mudança do CBF para diferentes regiões do cérebro em resposta a hipercapnia. Também, foi feita a identificação de áreas corticais responsáveis pelo controle voluntário da respiração. Por fim, os mapas de B-CBV obtidos utilizando o contraste BOLD em resposta à apnéia foram capazes de refletir o volume sangüíneo local, embora, estudos para análise dos outros parâmetros que influenciam o sinal devam ser realizados. / The BOLD (Blood Oxygenation Level Dependent) signal, is the most used contrast mechanism of the so called functional Magnetic Resonance Imaging (fMRI). Although it indirectly measures neuronal activity, its response is directly related to cerebral blood flow (CBF), Cerebral Metabolic Rate of Oxygen (CMRO2) and Cerebral Blood Volume (CBV) and can be, in principle, used to map cerebral perfusion. Thus, the main purpose of this study was to investigate, quantitatively, some aspects of perfusional alterations in the human brain. These changes were mapped by changes in the BOLD signal as a result of a global and uniform stimulation: hypercapnia induced by breath holding paradigms. Magnetic resonance images were acquired in a 1.5 T scanner (Siemens, Magneton Vision) with EPI-BOLD fMRI sequences. It was analyzed the BOLD dependency on breath holding duration and differences on the BOLD signal due the employed breath holding techniques: breath holding after expiration or after inspiration. The regional variability of the BOLD signal propagation was also studied. Moreover, the signal was used to construct maps based on CBV information. It was possible to gain information about the BOLD signal behavior that respond to PaO2 and PaCO2 alterations. Besides, it was demonstrated its regional variations sensibility, which can be correlated with arterial reactivity or the rest CBV of this arteries. It was also possible acquire information about the temporal characteristics of CBF changes induced by hypercapnia across brain regions as well as the identification of cortical areas that were responsible to the voluntary breathing. Finally, the B-CBV maps that used the BOLD con-trast were able to reflect CBV information, although, it is necessary the study of other parameters that can influence the signal.

A tactile display system has been built with 25 contactors in a 5 × 5 array with 2mm spacing, designed to stimulate the fingertip. The drive mechanism for each contactor is a piezoelectric bimorph, allowing the display to use in functional magnetic resonance imaging experiments (fMRI). The amplitude and frequency of stimulation can be pre-set, and each contactor can be activated separately using a personal computer. The tactile produce a wide variety of time-varying spatial patterns of touch stimulation. The sensation is “natural” and the participants do not find the experience unpleasant. The psychophysics experiment and the first fMRI experiment involved identification of various patterns on the display: the tactile stimulus was stationary or moved in a circle or in a “random” trajectory with no obvious shape. Response was by push buttons. The second fMRI experiment focused on the relationship between the speed of tactile motion and the corresponding activation in the brain, using stimuli moving in a circular trajectory on the tactile display at various speeds in the range 2.9 to 77.9 mm s –1. In the psychophysics experiment, the mean identification score was 80% after only a few minutes’ practice. The results of the first fMRI experiment showed highly significant activations in primary and secondary somatosensory cortices for contrasts of circle or random stimuli with the rest condition; low significant activations in SI and SII were observed for the contrast of stationary stimuli with rest. Broca's area was found to be activated for circle and random stimulation but not for stationary stimulation. Results from the second fMRI experiment showed small speed-sensitive activations in the left side of the brain, mostly in the primary somatosensory cortex. The conclusion in present study was our tactile system can produce different types of tactile patterns and it works inside MRI scanner.

The oldest procedure for pain relief has been music. There is abundant behavioural evidence to support music’s pain relieving properties, however, studies to date have yet to investigate music-induced analgesia via imaging. Our first imaging study used thermal stimulation just below pain threshold in combination with various music stimuli, to determine whether music can affect neural activity in response to heat stimuli within brainstem and spinal cord regions. Differential responses to music stimuli were found within regions known for descending modulation, and familiar classical music had a unique effect on neural activity in these regions compared to unpleasant music, reverse music, and no music. This study confirmed that the emotional valence of music affects neural activity in the brainstem and spinal cord. The second study used a well-defined pain paradigm applied with or without favorite music to study the neural activity responses in the brain, brainstem, and spinal cord using imaging. Subjective pain ratings were significantly lower when painful stimuli were administered with music than without music. The pain condition alone elicited neural activity in brain regions consistently activated during similar pain studies. Brain regions associated with pleasurable music listening were activated including limbic, frontal, and auditory regions when comparing music to non-music pain conditions. In addition, neural regions showed activity responses indicative of descending modulation when contrasting the two conditions. These regions include the spinothalamic tract, dorsolateral prefrontal cortex (DLPFC), periaqueductal grey (PAG), rostral ventromedial medulla (RVM), and the dorsal gray matter of the spinal cord. The data suggest that music seems to engage mesolimbic and mesocortical brain regions to activate the descending pain modulation pathway. Lower subjective pain ratings corresponded to a greater suppression in the dorsal gray matter when listening to music. This is the first imaging study to characterize the neural response of pain and how it is mitigated by music listening, and brain and spinal fMRI are appropriate means to study pain processing and its modulation in the central nervous system. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-06-18 11:33:32.818

The principal aim of this research programme was to examine multiple components of competitive tennis players’ emotional responses to pre-performance music. To this end, four objectives were defined: First, to develop a grounded theory (Glaser & Strauss, 1967) of players’ use of music to manipulate emotional state; second, to examine the impact of altering music tempo and intensity on players’ affective and behavioural responses; third, to identify neural origins for these phenomena; and fourth, to elucidate the role of motoneuron excitability in behavioural responses observed. These objectives were realised in four interrelated studies. First, 14 players provided quantitative and qualitative interview, questionnaire, and diary data to detail their use of personally emotive music; a grounded theory and associated model were consequently developed to facilitate future research and practice. Participants used music to attain five broad emotional states, including psyched-up; this was associated with faster tempi and louder intensities (volumes). Study 2 was conceived to examine the effects of manipulating these variables on 54 players’ affective and behavioural states, using measures based on Russell’s (1980) affective circumplex and reaction times (RTs). Faster tempi elicited higher valence and arousal, loud intensity yielded higher arousal and shorter RTs; and higher arousal was associated with shorter RTs. Functional magnetic resonance imaging was utilised in Study 3 to identify neural bases for 12 participants’ emotional responses to the same music manipulations; emotion-processing, visuomotor and sensorimotor structures were activated under high-arousal conditions. Transcranial magnetic stimulation and electromyography were used in Study 4 to investigate changes in 10 participants’ corticospinal excitability as a result of listening to purposively selected music; optimised music elicited higher arousal and reduced corticospinal response latencies. The foremost contribution of this thesis is to show that music variables may be carefully selected and/or manipulated to maximise performance-facilitating emotional responses to music in tennis.

Previous studies have shown that not all surgical residents can acquire the required skills for performing laparoscopic surgery. Therefore, the training methods can be improved to accommodate trainees with different psychomotor abilities. The first step towards improving training methods is understanding the brain function in performing the laparoscopic surgery training tasks, which can be facilitated by neuroimaging methods such as functional magnetic resonance imaging (fMRI). In this study, a laparoscopic surgery training box for use in fMRI was developed. Experiments confirmed the fMRI-compatibility of the device. Nine right-handed subjects underwent fMRI while performing the surgical training tasks after ten practice sessions in a simulated fMRI environment. Behavioural and fMRI results confirmed the feasibility of using this simulator and revealed the neuroanatomical correlates associated with performing the training tasks. Accordingly, this study may facilitate the evidence-based development of strategies to improve the quality of laparoscopy training and assessment strategies.

Previous studies have shown that not all surgical residents can acquire the required skills for performing laparoscopic surgery. Therefore, the training methods can be improved to accommodate trainees with different psychomotor abilities. The first step towards improving training methods is understanding the brain function in performing the laparoscopic surgery training tasks, which can be facilitated by neuroimaging methods such as functional magnetic resonance imaging (fMRI). In this study, a laparoscopic surgery training box for use in fMRI was developed. Experiments confirmed the fMRI-compatibility of the device. Nine right-handed subjects underwent fMRI while performing the surgical training tasks after ten practice sessions in a simulated fMRI environment. Behavioural and fMRI results confirmed the feasibility of using this simulator and revealed the neuroanatomical correlates associated with performing the training tasks. Accordingly, this study may facilitate the evidence-based development of strategies to improve the quality of laparoscopy training and assessment strategies.