Esclerose mesial temporal é causa freqüente de epilepsia de difícil controle em adultos. Avaliamos em crianças o espectro clínico, eletrográfico e radiológico desta patologia. Para tanto foi realizada revisão bibliográfica e estudo retrospectivo de 44 crianças no Hospital das Clínicas de São Paulo. Em ambos observou-se: predomínio das crises epilépticas com parada da movimentação, automatismo oroalimentar e gestual, e fenômeno motor; freqüente antecedente de crise febril e de estado de mal epiléptico. Na casuística verificou-se ainda que a lesão foi mais freqüente à esquerda em pacientes: com primeira crise entre seis meses e cinco anos de idade, com crise febril complicada e com dificuldade escolar / Mesial temporal sclerosis is frequent cause of intractable epilepsy in adults. We evaluate the clinical , electrographic and radiological spectrum this pathology in children. Was realized bibliographic revision and retrospective study in 44 children of the Clinic Hospital of São Paulo. Was observed: predominance of seizures with decreased responsiveness, oroalimentary and gestural automatism, and motor phenomenon; febrile seizures and epileptic status like frequent antecedents. The casuistry revealed lesion more frequent at left side in patients: with first seizure between six month and five years old, with febrile seizures complex and with school difficulty

abstract: In this research, a new cutting edge wear estimator for micro-endmilling is developed and the reliabillity of the estimator is evaluated. The main concept of this estimator is the minimum chip thickness effect. This estimator predicts the cutting edge radius by detecting the drop in the chip production rate as the cutting edge of a micro- endmill slips over the workpiece when the minimum chip thickness becomes larger than the uncut chip thickness, thus transitioning from the shearing to the ploughing dominant regime. The chip production rate is investigated through simulation and experiment. The simulation and the experiment show that the chip production rate decreases when the minimum chip thickness becomes larger than the uncut chip thickness. Also, the reliability of this estimator is evaluated. The probability of correct estimation of the cutting edge radius is more than 80%. This cutting edge wear estimator could be applied to an online tool wear estimation system. Then, a large number of cutting edge wear data could be obtained. From the data, a cutting edge wear model could be developed in terms of the machine control parameters so that the optimum control parameters could be applied to increase the tool life and the machining quality as well by minimizing the cutting edge wear rate. In addition, in order to find the stable condition of the machining, the stabillity lobe of the system is created by measuring the dynamic parameters. This process is needed prior to the cutting edge wear estimation since the chatter would affect the cutting edge wear and the chip production rate. In this research, a new experimental set-up for measuring the dynamic parameters is developed by using a high speed camera with microscope lens and a loadcell. The loadcell is used to measure the stiffness of the tool-holder assembly of the machine and the high speed camera is used to measure the natural frequency and the damping ratio. From the measured data, a stability lobe is created. Even though this new method needs further research, it could be more cost-effective than the conventional methods in the future. / Dissertation/Thesis / Doctoral Dissertation Mechanical Engineering 2019

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.

Epilepsy is a neurological disorder that is characterized by aberrant electrical activity in the brain resulting in at least two unprovoked seizures over a period longer than 24 hours. Approximately 60% of individuals with epilepsy are diagnosed with temporal lobe epilepsy (TLE) and about one third of those individuals do not respond well to anti-seizure medications. This places those individuals at high risk for sudden unexpected death in epilepsy (SUDEP). SUDEP is defined as when an individual with epilepsy, who is otherwise healthy, dies suddenly and unexpectedly for unknown reasons. SUDEP is one of the leading causes of death in individuals with acquired epilepsies (i.e. not due to genetic mutations), such as TLE. Previous studies utilizing genetic models of epilepsy have suggested that circuitry within the vagal complex of the brainstem may play a role in SUDEP risk. Gamma-aminobutyric acid (GABA) neurons of the nucleus tractus solitarius (NTS) within the vagal complex receive, filter, and modulate cardiorespiratory information from the vagus nerve. GABAergic NTS neurons then project to cardiac vagal motor neurons, eventually effecting parasympathetic output to the periphery. In this study, a mouse model of TLE was used to assess the effect of epileptogenesis on GABAergic NTS neuron function and determine if functional alterations in these neurons impact SUDEP risk. It was discovered that mice with TLE (i.e. TLE mice) have significantly increased mortality rates compared to control animals, suggesting that SUDEP occurs in this model. Using whole cell electrophysiology synaptic and intrinsic properties of GABAergic NTS neurons were investigated in TLE and control mice. Results suggest that during epileptogenesis, GABAergic NTS neurons become hyperexcitable, potentially due to a reduction in A-type potassium channel current and increased excitatory synaptic input. Increases in hyperexcitability have been shown to be associated with an increased risk of spreading depolarization and action potential inactivation leading to neuronal quiescence. This may lead to a decreased inhibition of parasympathetic tone, causing cardiorespiratory collapse and SUDEP in TLE.

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Cette thèse a pour thème l'étude les mécanismes neurocognitifs impliqués dans la détermination de la latéralité intrinsèque d'objets. Dans une première étude, nous avons montré qu'une projection de son propre schéma corporel sur un objet est nécessaire pour en différencier la gauche de la droite. Cette inscription corporelle fut observée aussi bien pour des stimuli humains que non humains, suggérant que la présence d'axes intrinsèques à l'objet est suffisante pour y permettre la projection du corps. Une seconde étude nous a permis de mieux comprendre les mécanismes neuronaux de l'inscription corporelle, en utilisant une tâche de comparaison de formes identiques ou miroir différemment orientées. Les stimuli étaient soit des corps humains, soit des assemblages de cubes. La magnetoencephalographie (MEG) révéla une implication du lobe pariétal supérieur gauche dans l'incarnation et la transformation spatiale des deux stimuli. Par ailleurs, une contribution de l'aire motrice supplémentaire fut observée dans le cas des cubes. Ainsi, nous proposons de considérer le lobe pariétal supérieur comme le substrat neural d'un émulateur utilisant le schéma corporel afin d'encoder la latéralité d'un objet et de prédire les conséquences visuelles d'une transformation spatiale. La contribution additionnelle de l'aire motrice supplémentaire a probablement facilité la transformation de formes non familières, par l'envoi d'une commande motrice à l'émulateur visant à accroître la cohérence de l'objet tourné mentalement. Ces interprétations supportent l'idée d'une cognition incarnée dans les actions corporelles.

Many researchers have explored the way younger people perceive weight ratios using a variety of methodologies; however, very few researchers have used a more direct ratio estimation procedure, in which participants estimate an actual ratio between two or more weights. Of the few researchers who have used a direct method, the participants who were recruited were invariably younger adults. To date, there has been no research performed to examine how older adults perceive weight-ratios, using direct estimation or any other technique. Past research has provided evidence that older adults have more difficulty than younger adults in perceiving small differences in weight (i.e., the difference threshold for older adults is higher than that of younger adults). Given this result, one might expect that older adults would demonstrate similar impairments in weight ratio estimation compared to younger adults. The current experiment compared the abilities of 17 younger and 17 older adults to estimate weight ratios, using a direct ratio estimation procedure. On any given trial, participants were presented with two weights, and were asked to provide a direct estimate of the ratio, with the heavier in relation to the lighter. The results showed that the participants’ perceived weight ratios increased as a linear function of the actual weight ratios and that compared to younger adults, the older adults overestimated the weight ratios. The age-related overestimation was especially pronounced at higher weight ratios.

Purpose: Excessive day time sleepiness, sleep disorders and neurobehavior changes are common clinical observations in the patients with epilepsy. From literature review, they were highly related with epilepsy risk characteristics (age of onset, types or numbers of drugs, seizure frequency), co-morbidities or neuronal network changes. The serological biomarkers have been reported to reflect the phenomenon of seizure, while their correlations with neurobehavior changes were still not concluded. There were two purposes of this thesis. (1) To understand the relationship between sleep disturbance with day time performances (2) To understand the relationships between serological biomarkers, neurobehavior performances and neuronal networks in patients with temporal lobe epilepsy. Material and Methods: The study enrolled patients from epilepsy outpatient clinic. By using self-appreciated questionnaire (The Pittsburgh Sleep Quality Index, The Epworth Sleepiness Scale, Euroqol Quality of Life Scale-5D), we collected the characteristics of sleep related behavior and life quality changes and explored the relationship with epilepsy risk characteristics. In patients with temporal lobe epilepsy, we assessed the neurobehavior performances, measured the serological biomarkers (heat shock protein 70, S100£]protein, neuron specific enolase, brain derived neurotrophic factor, plasma and mitochondrial DNA) and brain magnetic resonance imaging. In statistical analysis, we compared the differences with age matched controls or performed correlation analysis among the parameters Result: One hundred and seventeen patients with epilepsy completed the sleep quality questionnaires. The results showed that 20 percent of patients had day time sleepiness, while the sleep disorder was prolong sleep latency and impaired sleep efficiency. In epilepsy characteristics, patients with complex partial seizure, intractable seizure or with multi-pharmacy were related with poor sleep quality. A total of 34 patients completed the serological, neurobehavior and brain magnetic resonance analysis. The results showed that patients with temporal lobe epilepsy had higher heat shock protein 70 and S100£]protein levels, while those with attacks more than twice per month had significant higher heat shock protein 70, S100£]protein and neuron specific enolase levels. Compared with the matched controls, the regions showing atrophy included hippocampus and parahippocampus, putamen, thalamus and supplementary motor areas. In correlation study, only heat shock protein 70 showed an inverse correlation with hippocampal volume (R square = 0.22, p = 0.007) after controlling for the effect of age. Conclusion: The study suggested that epilepsy risk characteristics, serological biomarkers, brain atrophic regions were important factors for day time sleepiness, sleep disturbances and neurobehavior changes in patients with epilepsy.

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.