Attention is a cognitive process essential to daily function. As attention encompasses an extremely broad array of cognitive subprocesses, there remains much to be discovered about the brain regions related to attention with neuroimaging. This thesis presents two studies that used functional magnetic resonance imaging to examine neural activity associated with different forms of attentional control. In the first study, we scanned healthy young adults while they performed the Stroop task, which measures selective attention, to investigate neural responses underlying unanticipated conflict detection. We found several regions across the frontal, parietal, and occipital lobes that became more active during states of unanticipated conflicts, relative to states of anticipated conflicts. These regions included the anterior cingulate, dorsolateral prefrontal cortex, angular gyrus, inferior parietal lobule, precuneus, lingual gyrus, and fusiform gyrus. Activity in these regions has previously been associated with attentional processes such as conflict detection, attention, orientation, and oddball detection. Our results therefore suggest that widespread areas of the cortex serve several cognitive processes involved in successfully monitoring and responding to unanticipated conflicts. In the second study, we tested young and cognitively healthy older adults with the Stroop task to determine whether aging affects the neural mechanisms underlying attentional lapses, defined as relatively longer response times. Like previous studies in young adults, we found regions in the default mode network exhibited greater activity as reaction time to stimuli increased. Attentional lapses were also preceded by decreased activity in regions related to attention, including the anterior cingulate and prefrontal cortices. Most importantly, young adults showed greater positive reaction time-modulated activity in default mode areas, while older adults exhibited greater positive reaction time-modulated activity in more prefrontal areas. Our results suggest that the neural correlates of attentional lapses change with healthy aging, reinforcing the idea of functional plasticity to maintain high cognitive function throughout the lifespan. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2013-08-22 11:33:32.418

Functional MRI was used to detect brain activations in the primary somatosensory cortex (SI) in response to a vibrotactile stimulus applied to the thumb (D1) and little finger (D5) of the right (R) and left (L) hands. Four studies were carried out with healthy subjects in order to determine the scanning and stimulation protocols that resulted in consistent and robust SI activity. It was found that a strong stimulus, compared to a weak stimulus, led to the SI activity being detected more frequently and at a more statistically significant level. Also, extending the scanning duration per digit further increased the T-scores. The SI activations for each digit showed multiple foci and were distributed throughout the SI area. However, a clustering occurred in separate centres for stimulation to RD1 and RD5 near the Brodmann area 1/Brodmann area 3 boundary. The Euclidean separations of the cortical digit representations for LD1-D5 and RD1-D5 were calculated on the basis of the `centre of mass' of the multiple activations. Observed separations ranged between 1.2 mm to 22.8 mm. A further vibrotactile fMRI study was carried out involving patients with complex regional pain syndrome (CRPS). It has been suggested an altered central processing mechanism is involved in the disease, possibly due to cortical reorganisation in the sensory/motor cortices. The most efficient experimental protocols from the healthy subject studies were used to determine if these cortical differences were present in four patients. Data were acquired over two scanning sessions, approximately four months apart. The study revealed multiple SI foci and overlapping between the digits in both the healthy and CRPS hands, similar to those observed in the first studies. Larger SI activations were detected in one patient, smaller SI activations were detected in another patient and two patients demonstrated cluster sizes in the normal range. The cluster sizes and the changes in size between the two scans suggest a correlation with the amount of pain experienced by the patients. A general lack of consistency in the results from all the studies may be attributed to the difficulty of reliably detecting SI activity at a field strength of 1.5 T.

Eating disorders are difficult to treat: there is still no NICE-approved first-line treatment for anorexia nervosa. In part this could be due to a lack of a compelling theoretical model to account for the development and dogged persistence of the illness. Sociocultural factors implicating western preoccupation with thinness and attractiveness are likely to play a contributory role, but cannot be by themselves causal in societies where such ideals are dominant. Recent theoretical models in neuroscience predict that predisposing neurobiological factors in early brain development may render some young people more vulnerable than others to universal psychosocial pressures, especially during adolescence. This dissertation reviews the existing evidence for abnormal neurobiological functioning in eating disorders, acknowledging that it is difficult to distinguish between the acute effects of starvation on the brain and possibly pre-existing underlying factors. Nevertheless, such empirical studies do support the development of a novel hypothesis implicating abnormal functioning of a neural network centred on the insula cortex in anorexia nervosa. The insula hypothesis is tested in a series of functional imaging studies using Single Positron Emission Computed Tomography (SPECT) indicating focal abnormalities in the temporal region that persist following weight restoration treatment and correlate with neuropsychological deficits. A subsequent study using higher resolution functional Magnetic Resonance Imaging (fMRI) lends further partial support to the insula hypothesis (in three out of four tasks) and also implicates additional brain structures in the basal ganglia. These findings, if replicated, could contribute to the development of novel therapeutic approaches to the treatment of anorexia nervosa, including realtime fMRI and mindfulness-based approaches, both of which have been shown to modulate insula activation. The studies presented here could hopefully also help to reduce the stigma and shame so often associated with eating disorders, for the benefit of sufferers and their families.

Although several studies have characterized common and unique neural circuitry associated with social and non-social emotions, none to date have attempted to differentiate between social emotions that occur in very different contexts. Grieving the death of a loved one and being a target of perceived discrimination may implicate potentially distinct social processes (e.g., attachment versus affiliation). When examined separately, prior neuroimaging research has shown that both grief and perceived discrimination involved diffuse brain regions implicated variously in social stress processing and emotion, however no studies to date have directly compared these experiences. In the present study, we examined neural correlates of grief and perceived discrimination among South Asian women (n = 10), using an idiographic emotional imagery task. Grief-related imagery elicited activation in the precuneus, midbrain, dorsal striatum, and thalamocingulate regions, consistent with previous neuroimaging studies of grief and attachment. Participants showed greater activation in the anterior cingulate, hippocampus, occipital cortex, and cerebellum during Grief relative to Discrimination. We observed dorsomedial prefrontal cortex (dmPFC) activation in Discrimination>Neutral, which may reflect greater self-regulatory effort involved in coping with discrimination experiences. Greater temporal pole and amygdala activation in the Discrimination condition were associated with greater lifetime perceived discrimination, poorer self-reported physical health, and more depressive symptoms. Results of this pilot study suggest that there are observable differences in the brain response to these two types of social stressors, suggesting future directions for a more fine-grained view of the mechanisms through which the social environment may influence health and well-being.

Deficits in phonology are among the most common and persistent impairments in aphasia after left hemisphere stroke, and can have significant functional consequences for spoken and written language. While many individuals make considerable gains through physiological restitution and in response to treatment, the neural substrates supporting phonological performance in the face of damage to critical language regions is poorly understood. To address this issue, we used BOLD fMRI to measure regional brain activation in a case series of individuals with aphasia after left MCA stroke during a phonological task. The results of this study support the idea that damage to even a portion of the phonological network results in impaired phonological processing. We found that individuals with left perisylvian damage tend to rely on the residual left-hemisphere language network, and typically recruit regions associated with domain-general cognitive processing which fall outside of the left-hemisphere language network. However, recruitment of these regions did not necessarily enhance phonological processing. Rather, more successful phonological processing outside the scanner was associated with recruitment of a language region in right posterior middle temporal gyrus and a region in left occipital pole. More successful phonological processing inside the scanner was associated with additional recruitment of the left supramarginal gyrus within the healthy control network, engagement of bilateral intraparietal sulcus from the multi-demand network, and up-regulation of the right-hemisphere network of regions homotopic to the left-hemisphere language network seen in the healthy control group. These findings emphasize the contributions of residual components of the left-hemisphere language network, engagement of a non-linguistic domain-general multi-demand network, and the participation of the non-dominant right-hemisphere language network in successful phonological processing in chronic aphasia after stroke.

Clinical care for major depressive disorder (MDD) would be greatly improved if we had reliable clinical predictors of individual antidepressant treatment outcome. While, at the present time, no biomarkers have sufficiently proven utility to be ready for clinical application, several neuroimaging modalities have shown promise for such development. Attempts to combine the recently developed modality of resting-state functional Magnetic Resonance Imaging (rs-fMRI) with pharmacological challenges to explore the impact of antidepressants on resting-state brain connectivity have just begun (McCabe et al., 2011a, McCabe et al., 2011b). The aim of the current study was to investigate the effects of a single dose of the SSRI (selective serotonin reuptake inhibitor) escitalopram on resting-state functional connectivity in health.

Neurosurgery is an effective method for prolonging life and improving outcomes for patients with brain tumors. However, this option bears the risk of damaging areas of eloquent cortex, areas associated with motor and language tasks that, when lesioned, will result in a functional deficit for the patient. Functional magnetic resonance imaging (fMRI) is a valuable tool in the localization of eloquent cortex for preoperative neurosurgical planning. Through use of this modality of functional neuroimaging, the neurosurgeon can adjust the surgical trajectory to incur the least amount of damage to sites of functional activity. The supplementary motor area (SMA) is one such site of eloquent cortex that must be visualized preoperatively due to the risk of postoperative deficit with lesions in this area. However, due to both the effects of tumor pathology and naturally occurring interindividual variability, the SMA’s location and functional fingerprint can be highly variable. We present a study in which patients with frontal tumor (n=46) underwent task-based fMRI for motor and language network mapping. The patient-specific functional data were normalized and evaluated using ROI analysis to illustrate group-level activation patterns within the SMA during the language and motor tasks. The results illustrate a distinct pattern of activation including a rostro-caudal organization of language and motor activation, overlapping extent cluster volumes throughout the two functional subdivisions of the SMA, the pre-SMA and SMA proper, and discrete activation foci.

Muito embora a eletroencefalografia continue sendo amplamente empregada no estudo e diagnóstico da epilepsia, as imagens funcionais de ressonância magnética tornaram-se uma das principais ferramentas de acesso não invasivo às funções normais do cérebro. Atualmente, é uma realidade clínica a aplicação dessas técnicas para o mapeamento pré-cirúrgico e também nos estudos básicos em neurociência. Entretanto, em muitos casos é necessário um estudo combinado dessas duas técnicas. De um modo geral os sinais obtidos em experimentos de ressonância magnética funcional (fMRI) devem ser processados a fim de revelar o mapa de ativação, relativo ao estímulo aplicado. Entretanto até a presente data não há um método consensual para a análise dos sinais de fMRI. Nesse sentido, apresentamos nesse trabalho dois novos métodos para a análise de sinais de fMRI baseados em conceitos de teoria de informação utilizando a entropia de Tsallis. O primeiro método consiste em uma alternativa para análise de fMRI obtida através de paradigmas evento-relacionados, sem que a forma da resposta ao estímulo seja levada em conta. Utilizando a teoria de informação, consideramos a evolução temporal da entropia do sinal sem realizar nenhuma hipótese sobre a forma da função de resposta. O método se mostrou capaz de discriminar regiões ativas e não ativas em paradigmas motores e visuais. Através de simulações, observamos que o nosso método se apresenta mais estável com o o aumento do ruído quando comparado com o método clássico. O segundo método que desenvolvemos para análise de dados de fMRI (paradigmas em bloco) baseia-se no conceito de informação mútua generalizada (GMI). Neste sentido, obtivemos um amplo espectro de resultados dependentes do parâmetro q de Tsallis. Assim, realizaram-se análises em dados simulados de modo a construir as curvas características de um sistema receptor (curvas ROC). Determinando os parâmetros que avaliam a qualidade das curvas otimizamos os valores de q . Tanto os resultado obtidos das simulações quanto os obtidos através de imageamento em voluntários forma analisados comparando-se os métodos clássicos com o GMI. Outrossim, a determinação do foco epileptogênico é de grande interesse no diagnóstico e profilaxia da epilepsia. Essa determinação envolve muitas vezes a detecção da atividade anormal que ocorre entre as crises (atividades interictais). Esta tarefa demanda muito tempo dos neurofisiologistas por ser realizada através de inspeção visual. Os eventos anormais mais comumente observados apresentam duas componentes, uma de alta freqüência (ponta) e outra de mais baixa (onda). Assim sendo, desenvolvemos um algoritmo que se utiliza do conceito de multiresolução para detecção automática das atividades anormais e localização aproximada do foco epileptogênico. Como resultado, a localização do foco obtida através do algoritmo coincidiu com a indicada pelo neurofisiologista através da metodologia usual. As duas técnicas EEG e fMRI juntamente com os métodos propostos constituem o primeiro passo para um sistema de auxílio diagnóstico e planejamento cirúrgico.

A epilepsia do lobo temporal (ELT) é a forma mais comum de epilepsia e a mais resistente ao tratamento medicamentoso. Existem diversos tipos de drogas anti-epilépticas usadas no controle das crises. Entretanto, em alguns casos, esse tipo de tratamento não é eficaz e a cirurgia para remoção da zona epileptogênica (ZE) pode ser uma alternativa recomendada. A ZE é definida como aquela onde as crises são originadas. Trata-se de um conceito teórico e, atualmente, não existem técnicas capazes de delimitá-la precisamente. Na prática, exames de EEG, vídeo-EEG, MEG, SPECT, PET e diversas técnicas de MRI, em especial as funcionais, têm sido usados para mapear zonas relacionadas à ZE. Contudo, em alguns casos, os resultados permanecem não convergentes e a determinação da ZE inconclusiva. Desse modo, é evidente a importância do surgimento de novas metodologias para auxiliar a localização da ZE. Assim, pois, o objetivo deste trabalho foi desenvolver dois métodos para a avaliação da ZE, ambos baseados na imagem funcional por ressonância magnética. No primeiro, investigamos possíveis alterações da resposta hemodinâmica (HRF) quando da modulação da pressão parcial de CO2. Para tanto, fizemos um estudo sobre 22 pacientes com ELT e 10 voluntários assintomáticos modulando a pressão parcial de CO2 sanguíneo cerebral por um protocolo de manobra de pausa respiratória e outro de inalação passiva de CO2/ar. Os resultados mostram que o tempo de onset da HRF tende a ser maior e a amplitude da HRF tende a ser menor em áreas do lobo temporal de pacientes com ELT quando comparados com os dados de voluntários assintomáticos. Além disso, os resultados mostram mapas de onset individuais coincidentes com exames de SPECT ictal. O segundo estudo foi baseado em medidas de EEG-fMRI simultâneo. Neste, avaliamos a relação entres as potências dos ritmos cerebrais alfa e teta (EEG) e o contraste BOLD (fMRI) de 41 pacientes com ELT e 7 voluntários assintomáticos em estado de repouso. A análise da banda alfa mostrou correlações negativas nos lobos occipital, parietal e frontal tanto nos voluntários quanto nos pacientes com ELT. As correlações positivas nos voluntários foram dispersas e variáveis em ambos hemisférios cerebrais. Por outro lado, encontramos forte correlação positiva no tálamo e ínsula dos pacientes com ELT. Na análise da banda teta observamos correlações positivas bilaterais nos giros pré e pós central de voluntários. Ainda, foram observados clusters no cíngulo anterior, tálamo, ínsula, putamen, em regiões parietais superior, frontais e giros temporais. Também, utilizamos um cálculo de índice de lateralização (IL) no lobo temporal em confrontos entre pacientes com ELT à direita, pacientes com ELT à esquerda e voluntários assintomáticos. Verificamos que os ILs, utilizando os clusters obtidos nas análises em teta, foram coincidentes com o diagnóstico clínico prévio da localização da ZE em todas as análises dos grupos de pacientes com ELT à direita, e na maioria do grupo de pacientes com ELT à esquerda. De forma geral, verificamos que o método de hipercapnia se mostrou ferramenta interessante na localização da ZE comprovada pelos coincidentes achados pela avaliação de SPECT. Inferimos que o maior tempo de onset e menor amplitude da HRF observadas nos pacientes em relação a voluntários possam estar relacionados a um stress vascular devido à recorrência de crises. Já o método de ritmicidade alfa e teta proposto parece promissor para ser usado na determinação da lateralização da ZE em pacientes com ELT. / Temporal lobe epilepsy (TLE) is the most common and resistant form of epilepsy to anti-epileptic drug. There are several types of anti-epileptic drugs used in seizure control. However, in some cases drug treatment is not effective and surgery to remove the epileptogenic zone (EZ) is a recommended alternative. EZ is a theoretical concept and there are many techniques that have been applied to enclose it precisely. In practice, EEG, video-EEG, MEG, SPECT, PET and various MRI techniques, especially functional MRI (fMRI), have been used to map areas related to EZ. However, in some cases, the results remain non-convergent and the EZ, undefined. Therefore, the use of new methodologies to assist the location of EZ have been proposed. Herein, our goal was to develop two methods for assessing the EZ. The first one was designed to access changes in the hemodynamic response (HRF) of the EZ in response to hypercapnia. 22 patients with TLE and 10 normal volunteers were evaluated by modulating the partial pressure of CO2 during the acquisition of fMRI in a breathing holding and a passive inhalation CO2/air protocols. The results show increased onset times and decreased amplitude of the HRF in the temporal lobe of TLE patients compared with asymptomatic volunteers. Moreover, most patients had onset maps coincident with ictal SPECT localizations. The second proposed study was based on simultaneous EEG-fMRI acquisitions. The relationship between powers of alpha and theta bands (EEG) and BOLD contrast (fMRI) was investigated in 41 TLE patients and 7 healthy controls. Alpha band results show a consistent negative correlation in the occipital, parietal and frontal lobes both in controls and TLE patients. In addition, controls show disperse positive correlations in both hemispheres. On the other hand, TLE patients presented strong positive correlations in the thalamus and insula. Theta band analysis, in controls, primarily show positive correlations in bilateral pre-and post-central gyri. In patients, robust positive correlations were observed in the anterior cingulate gyrus, thalamus, insula, putamen, superior parietal, frontal and temporal gyri. Moreover, the lateralization index (LI) indicates a coincidence between the side of the EZ evaluated by clinical diagnosis and clusters detected in the theta band. In conclusion, the hipercapnia study showed to be an interesting tool in locating EZ and the results are similar to SPECT findings. The longer onset and lower amplitude of the HRF observed in patients may be related to a vascular stress due to the recurrence of seizures. Furthermore, alpha and theta rhythms may be a promising tool to be used in determining the lateralization of EZ in patients with TLE.

Thesis advisor: Elizabeth A. Kensinger / Neural and behavioral responses to emotional stimuli often are discussed within an evolutionary framework. Although some of the information that elicits an emotional response is likely to have had evolutionary significance (e.g., snakes, spiders), many other stimuli would not have been evolutionarily relevant (e.g., guns, grenades). The present study re-analyzed data from two fMRI studies (Kensinger et al., 2007; Kensinger & Schacter, 2008) to examine whether the neural systems that respond to emotional stimuli differ depending upon whether those stimuli were of phylogenetic or ontogenetic significance. The results revealed that when stimuli were ontogenetic, activity was increased in regions of the anterior cingulate and orbitofrontal cortices. By contrast, when stimuli were phylogenetic, activity was increased in a region spanning the lingual and fusiform gyri. These results suggest that there can be differences in how emotional stimuli are processed, and those differences can depend upon the stimuli’s evolutionary significance. / Thesis (BA) — Boston College, 2009. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Psychology Honors Program. / Discipline: Psychology.