M.A. (Clinical Psychology) / Attention deficit hyperactivity disorder (ADHD) is a form of psychopathology characterised by difficulties with hyperactivity, attention and behavioural inhibition. Although ADHD has been historically considered a disorder specific to children, the contemporary consensus among researchers is that, in some cases, ADHD may persist into adulthood. Neurologically, ADHD is associated with deficits in the executive functions, located in the frontal lobe. Cortical arousal, which refers to the level of neuronal activity in the cerebral cortex and is measurable using electroencephalograph machinery (EEGs), is usually lower in the frontal lobes in those with ADHD when compared to individuals without the disorder. With regards to anxiety disorders, which are dysfunctional variations in the normal fear response, the aetiology of the pathologies in this category are multifaceted and complex. At the neurological level, however, there is a clear link between anxiety disorders and hypervigilance, which is characterised by high cortical arousal in the frontal lobes. Despite the fact that, at face value, it seems impossible for an increase and decrease in cortical arousal to occur simultaneously, ADHD is often diagnosed alongside anxiety disorders, and it is this anomaly which is the focus of this study. Electroencephalograph machinery (EEGs) are able to measure levels of cortical arousal using electrodes placed on the scalp. This research employs this equipment in order to elucidate on how cortical arousal manifests during a task that demands significant involvement from the frontal areas of the brain. A quasi-xperimental research design using non-parametric statistics (Mann-Whitney U Test) was used in order to compare the levels of cortical arousal between 4 groups of 5 research participants with either ADHD, an anxiety disorder, comorbid ADHD and anxiety and no discernible psychopathology. The significant results found in this study point to the fact that, in cases where ADHD and anxiety disorders occur comorbidly, there is a possibility that the anxiety component enables an individual to achieve more pronounced levels of attention, concentration and focus than normal participants and those with ADHD alone...

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The focus of this project falls largely within the realm of investigating the development of brain-cognition relations from a developmental cognitive neuroscience perspective. There were two main goals of this study. First, this study focused on the regional differences in baseline-to-working memory task brain electrical activity and specifically investigated the hypothesis that there would be an increasing specificity of task EEG power between 3½ and 4½ years of age. The second goal of this study was to investigate the sources of variability in working memory function and to specifically examine the contributions of task-related EEG, the regulatory dimensions of temperament, and linguistic ability to the prediction of working memory performance. This second study objective included an investigation of the relation between working memory and each of these variables (1) separately, (2) in conjunction with age, and (3) collectively to examine any multivariate contributions to the explanation of variance in working memory function in early childhood. The results of this study provided some support to the increasing specificity of baseline-to-task EEG power hypothesis. Specifically, an increase in brain electrical activity was found for four scalp regions at age 4 and only two regions at age 4½. These findings coupled with previous work indicating an increase in task brain electrical activity for only one region at age 4½ suggest that cortical specialization is occurring during the early childhood years. With regard to the investigation of sources of variability working memory function, age, brain electrical activity, temperament, and linguistic functioning were all found to be meaningful variables in the explanation of variance in working memory. However, linguistic functioning " and specifically language receptivity " was found to be the strongest and most meaningful associate of working memory function. Additional findings of interest included the differential associations demonstrated between working memory and temperament for each age group and also an increase in the strength of the relation between working memory and language across the three ages. / Ph. D.

Implementation intentions have been shown to improve prospective memory performance among a variety of populations. In two studies, the effectiveness of implementation intentions was examined among young and older adults. In Experiment 1 64 young adults were placed into one of four instructional conditions (Read-Only, Imagery, Implementation Intention, Combined) before completing a laboratory-based prospective memory task. Results reveal that prospective memory performance improves under each of the three experimental conditions, but that there is no additional benefit of combining imagery with implementation intentions. In a novel finding, imagery alone produced improvements comparable to implementation intentions. Experiment 2 investigated the effect of implementation intentions among 32 older adults, who were characterized as possessing high- or low-frontal function based on neuropsychological test performance. Implementation intentions improved prospective memory among both groups, regardless of frontal function. The results of these studies suggest that implementation intentions can improve prospective memory among both young and older adults. Importantly, these findings reveal that imagery alone may be an effective means of improving prospective memory. Additionally, that implementation intentions improved prospective memory among older adults, regardless of frontal function, raises important questions about potential mechanisms underlying the effectiveness of implementation intentions.

Pacientes com epilepsias farmacorresistentes estão cada vez mais se beneficiando do tratamento cirúrgico, dado o avanço nas técnicas de diagnóstico. Com a cirurgia, busca-se tornar o paciente livre de crises sem que para isso sejam provocados déficits neurológicos secundários. Para que isso seja alcançado é fundamental que a região cerebral epileptogênica seja delimitada com precisão. Os principais meios que o neurofisiologista dispõe para localizar a zona epileptogênica (ZE) na avaliação pré-cirurgica são a eletroencefalografia escapelar e a ressonância magnética (RM). Nos casos em que a RM não apresenta lesões ou os dados obtidos são conflitantes as técnicas de imagem funcional tais como a tomografia por emissão de fóton único (SPECT) e a tomografia por emissão de pósitron passam a ter um papel decisivo. O SPECT crítico apresenta uma imagem da perfusão sanguínea cerebral no momento da crise evidenciando, assim, as áreas cerebrais que estavam mais ativas. A técnica de subtração do SPECT intercrítico do crítico e o corregistro deste resultado coma RM do paciente (SISCOM) tem sido estudada como uma maneira de aumentar a sensibilidade e especificidade do SPECT crítico. Este trabalho buscou estudar e validar o papel dos SPECT crítico, intercrítico e SISCOM na localização da ZE. Todos os pacientes com suspeita de epilepsias refratária do lobo frontal baseada nos outros exames, operados no período de 2007 a 2011 e que realizaram um SPECT crítico e um intercrítico foram considerados nesse estudo. Para cada SPECT crítico foi realizado o SISCOM e o resultado comparado com o local da ressecção e o resultado cirúrgico sendo calculadas as métricas de desempenho diagnóstico de cada um dos métodos de neuroimagem funcional. No total foram operados 14 pacientes e 5 tiveram um bom resultado cirúrgico. O SPECT crítico apresentou 40% de sensibilidade e 88,9% de especificidade enquanto que o SPECT intercrítico apresentou 40% de sensibilidade e 66,7% de especificidade. O SISCOM foi o método com melhores parâmetros de desempenho apresentando uma sensibilidade de 60% e uma especificidade de 88,9%. Esses resultados coadunam com os dados encontrados na literatura em que o SISCOM é o estado da arte na interpretação do SPECT crítico e sugerem que o SISCOM tem potencial para ser utilizado na avaliação pré-cirurgica de pacientes com suspeita de epilepsias do lobo frontal. / The surgical treatment for patients with intractable epilepsies has become more efficient with the evolution of diagnosis techniques. The surgery aims at rendering the patient free of seizures, without postoperative neurological deficits. In order to accomplish this, it is of major importance to precisely delineate the epileptogenic zone (EZ). The main exams the neurologists use in order to find the EZ in the pre-surgical evaluation are the scalp electroencephalography and the magnetic resonance imaging (MRI). However, in cases where the MRI doesn\'t show any lesion or there are conflicting data, functional imaging such as Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography techniques play a crucial role. Ictal SPECT shows a snapshot of cerebral blood perfusion during the seizure, highlighting the most active areas during the ictus state and it has been shown this technique is useful in localizing the EZ in frontal lobe epilepsy cases. Sensitivity and specificity of ictal SPECT might be improved by a developed Computer Aided Diagnosis tool that subtracts the interictal SPECT image from the ictal one and coregisters the result with the MRI (SISCOM). In the present study, we aimed to evaluate the contribution of SISCOM to the pre-surgical evaluation in frontal lobe epilepsies. We considered for this study patients submitted to frontal lobe epilepsy surgery at our institution between 2007 and 2011 and with at least one ictal and one interictal SPECT. 14 patients were included and only 5 had a good outcome after the surgery. The ictal SPECT had a sensibility of 40% and specificity of 88,9% while the interictal SPECT showed a sensibility of 40% and a specificity of 66,7%. The sensitivity of the SISCOM tool was 60% and the specificity 88,9%.These results agree with the literature showing that SISCOM is the state-of-the-art in interpreting the ictal SPECT and has the potential to be used during presurgical evaluation of patients being considered for surgical treatment of frontal lobe epilepsy.

Damage to the ventromedial prefrontal cortex (vmPFC) can lead to disturbances in personality, emotional dysregulation, impairments in social conduct, and difficulties in decision-making. Many researchers have likened the conduct of individuals with vmPFC lesions to that of criminal psychopaths, labeling the effects of vmPFC damage “pseudopsychopathy” or “acquired sociopathy.” However, although psychopathy—a condition marked by a distinct mosaic of antisocial personality traits and behaviors—has been studied and characterized as a psychological and behavioral disorder by many researchers, the overlap between acquired sociopathy and psychopathy remains ambiguous. This study assessed the severity of psychopathic personality traits in neurological patients with acquired damage to the vmPFC using both informant-report and self-report measures. On both informant-report and self-report measures, individuals with vmPFC damage showed no significant elevations across a wide range of psychopathic traits relative to demographically-matched neurologically healthy comparison participants and patients with damage outside of the vmPFC. The results showed only one trait, Fearlessness, that was significantly higher in patients with vmPFC lesions relative to the neurologically-healthy comparison group.

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Feeding behavior is a complex phenomenon involving homeostatic signals, and non-homeostatic inputs such as visual cues. In primates, exposure to food-related sensory cues has been shown to elicit cephalic phase responses as well as trigger central appetitive processing, in a motivationally-dependent manner. Neural structures consistently implicated in such responses and/or in the regulation of ingestive behavior in general, in both monkeys and in humans, include the amygdala, insula, striatum, hypothalamus, and frontal and occipital cortices. In humans however, the cerebral response to visual food stimulation remains minimally explored. / Functional Magnetic Resonance Imaging (fMRI) provides information about state-dependent changes in local neuronal activity in vivo. Using fMRI, the present dissertation examined changes in human brain activity to food and nonfood pictures following the pharmacological induction of hunger with the orexigenic hormone ghrelin (Study 1), and following manipulation of the cognitive state of food expectation (Study 2). / Our data reinforce the involvement of a distributed frontal-limbic-paralimbic circuit in the central processing of food imagery, under both experimental conditions. The first study revealed that intravenous ghrelin administration potently modulated food-associated neural responses III areas involved in reward, motivation, memory, and attention (amygdala, insula, orbitofrontal cortex, striatum, hippocampus, midbrain, visual areas). This suggests that metabolic signals such as ghrelin may promote food consumption by enhancing the appetitive response to food cues via engagement of the hedonic network. / The second study revealed that brain regions activated in the 'expectant' state (i.e. when subjects were anticipating food reward) were at least partially dissociable from those in the 'not expectant' state. In particular, recruitment of the dorsolateral prefrontal cortex, a principal component in the cognitive control network, exclusively in the 'not expectant' condition, may signal an attempt to suppress appetite in the absence of food expectation. Areas of convergence were observed in the amygdala and insula. / Obesity is rapidly becoming the major cause of excess mortality worldwide; therefore, understanding how the central nervous system controls appetite and nutrient consumption is of considerable interest. The projects in this thesis offer significant insights regarding the effects two select factors (one intrinsic and the other extrinsic) on the neural reaction to visual food stimuli, in healthy male participants.

Pyrithiamine-induced thiamine deficiency in rats is a well-established animal model of Wernicke's Encephalopathy (WE). This thesis project, submitted as four articles, presents an examination of metabolic events that contribute to the selective neuronal lesions observed in the medial thalamus (MT) of thiamine-deficient (TD) rat. In addition, the phenomenon of glucose-precipitated worsening of neurological status in WE patients (Wallis et al., 1978; Watson et al., 1981) is explored. / Lactate accumulation is known to occur selectively in regions of the TD brain, which ultimately express neuronal cell death (McCandless, 1982; Munujos et al., 1996). In Article 1, the metabolic origin and cellular localization of region-selective lactate accumulation in the MT of TD rats was studied using combined 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Parallel studies were performed to examine the effects of glucose loading on regional brain lactate synthesis in TD animals. Thiamine deficiency caused focal increases in the de novo synthesis of lactate via elevated glycolytic flux in the MT, while contribution via pyruvate recycling and the periphery remained nominal. Lactate levels remained unaltered in the frontal cortex (FC), a brain region that is spared in thiamine deficiency. Administration of a glucose load intensified the selective increases in lactate de novo synthesis and accumulation in the MT of TD rats, positing a role for lactic acidosis in the glucose-precipitated worsening of neurological status in TD patients. Accordingly, Article 2 addresses the effect of glucose loading on local cerebral pH in the vulnerable MT, compared to the FC, of TD rats. Administration of a glucose load resulted in detrimental decreases in regional pH selectively in the MT, implying that alterations of brain pH contribute to the pathogenesis of thalamic neuronal damage and consequent cerebral dysfunction in WE. / Region-specific alterations in the steady state levels of cerebral amino acid neurotransmitters have been well-documented in experimental animal models of thiamine deficiency (Butterworth et al., 1979; Butterworth & Heroux, 1989; Gaitonde et al., 1975; Plaitakis et al., 1979); however, the dynamics of these changes have never been systematically explored. In Article 3, we examined the metabolic fluxes through thiamine-dependent pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) using multinuclear NMR spectroscopy. Furthermore the cellular localization of the metabolic changes in relation to regional vulnerability to thiamine deficiency was addressed. Our studies clearly demonstrate that early decreases m metabolic flux through alpha-KGDH result in commensurate declines in aspartate concentrations in the MT of TD rats. Impairments to PDH flux manifest secondarily to the metabolic block at alpha-KGDH, likely due to depleted oxaloacetate pools. As a result of impaired pyruvate oxidation, declines in the de novo synthesis of glutamate and GABA ensue. The present findings also suggest that inhibition of flux through alpha-KGDH in TD brain occurs primarily in the neurons, while astrocytes possess compensatory mechanisms, i.e. the anaplerotic pathway, to replenish oxaloacetate concentrations via metabolic pathways that do not involve thiamine-dependent enzymes. / In Article 4, we investigated the regional effects of thiamine deficiency on the activity of thiamine-dependent branched-chain alpha-ketoacid dehydrogenase (BCKDH) and the resultant effects on regional cerebral branched-chain amino acid (BCAA) oxidation. Thiamine deficiency resulted in significant impairments in BCKDH activity; while parallel studies on enzyme distribution confirmed a lower oxidative capacity for BCAAs in the MT compared with the Fe. / The data presented in these four articles confirm and extend findings for the region-selective impairments in thiamine-dependent metabolic processes as the foundation of vulnerability of the MT to thiamine deficiency. In addition, glucose loading of TD rats exacerbates both lactic acidosis and impaired pyruvate oxidation in this vulnerable brain region, positing a role for these processes in the glucose-precipitated worsening of neurological status in TD patients. Impaired oxidative metabolism of glucose and BCAAs in the MT leads to the accumulation of potentially harmful metabolic intermediates, contributing to the mitochondrial dysfunction, cellular energy failure and ultimately neuronal cell death observed in thiamine deficiency.

Motor response selection is the process by which an intention to act is transformed into an action; this multifaceted process occurs at the interface between cognitive and motor systems. Despite the importance of response selection, the nature and neural implementation of this process is still a subject of debate (Thompson-Schill et al, 1997; Botvinick et al., 2001; Rushworth et al., 2004; Nachev et al., 2007). While previous research has demonstrated that the selection of finger movements relies on a distributed network involving premotor and prefrontal areas, the specific contribution of these regions, however, remains unclear. It is also unclear if the selection of words engages similar processes as the selection of finger movements, that is, if response selection is a domain-general or a domain-specific process. In order to address these issues, a set of four complementary studies using functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) was developed in which different factors affecting response selection were examined: selection mode, response type (words vs. oral movements), attention and response competition (conflict). / The results of these studies provide new insights into the neural architecture of response selection by uncovering the respective contribution of premotor areas (pre-SMA and PMA) and prefrontal areas (DLPFC and IFG). A preliminary two-stage model of response selection is proposed, in which the PMA is generating a set of response alternatives from which the pre-SMA performs selection using one of two different mechanisms (response facilitation and response inhibition). In general, these findings do not support the hypothesis of a medio-lateral gradient of control (Goldberg, 1985) but confirm the fundamental role of the lateral (PMA) and medial (pre-SMA) premotor areas in the process of selecting motor responses. / Importantly, the results also demonstrate that selection is a domain-general (response-independent) process. Uncovering the general, multifaceted nature of brain mechanisms is essential to reveal the basic units of control in the central nervous system; this knowledge is fundamental to broaden current understanding of the basic brain operations that are used to produce language. Theoretical and clinical implications of these findings are discussed.