<div>Ketogenic diets (KDs) are high-fat low-carbohydrate diets that can exert positive effects on physical and neurological health. The more established therapeutic effects of KD are for treating epilepsy and diabetes. However, KD protective effects may apply to other inflammation related disorders associated with Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation, such as mood disorders. Chronic stress has been shown to elevate cytokine levels, disrupt neuroendocrine homeostasis, and cause anxiety and depressive-like behavior in animal models. In vitro experiments have shown that ketone bodies, a metabolite produced while on KD, can prevent the production of cytokines elevated in response to chronic stress and other pre-clinical experiments have suggested that ketone bodies can prevent anxiety-like behavior. Although this suggests that KDs have anti-inflammatory and mood stabilizing potential, these effects have yet to be explored. In this experiment, we assessed the behavioral and neuroendocrine effects of KD using male and female Long-Evans rats. Animals underwent three weeks of Chronic Mild Stress (CMS) while on KD or control Chow (CH). Body weight and food intake data were recorded daily, and depressive-like behaviors were assayed after the three weeks. Plasma Beta-Hydroxybutyrate (HB), Corticosterone (CORT) and Interleukin-1 beta (IL-1) were measured after behavior testing, along with hypothalamic Corticotropin-Releasing Hormone (CRH) and Neuropeptide Y (NPY) mRNA expression. CMS induced weight loss and reduced food intake in the control-diet groups, however the KD-fed male and female rats were resistant to CMS-induced weight loss and reduced food take. Female rats fed KD were protected from CMS-induced reductions in plasma CORT and hypothalamic NPY expression. Collectively, these data suggest anti-depressant potential of KDs against chronic stress, particularly in females. </div>

<p>Deficits in impulse control and decision-making have been implicated in the development and maintenance of alcohol use disorders (AUDs). Individuals with AUD often make disadvantageous choices under conditions of probabilistic risk. The Iowa Gambling Task (IGT) is often used to measure risky decision-making, in which impaired individuals tend to favor large, infrequent rewards even when punished for these choices, rather than smaller, safer, and more advantageous rewards. It remains poorly understood if these deficits are behaviors under genetic control and if ethanol intoxication may alter decision-making. High and Low Alcohol Preferring (HAP3 and LAP3, respectively) mice were trained on a novel gambling task to investigate these possible influences. In Experiment 1, HAP3s and LAP3s responded for a 0.1% saccharin solution, choosing between a risky and a safe option. Importantly, choosing the risky option was meant to be ultimately disadvantageous. In Experiment 2, these same HAP3 mice responded for saccharin or saccharin plus 10% ethanol. Contrary to hypothesis, LAP3s preferred the risky option more than HAP3s. Alcohol increased preference for the risky lever, but only in male mice. HAP3 preference for the safe lever may be explained by higher motivation to obtain sweet rewards, or higher overall avidity for responding. Ethanol-induced changes in male risk behavior may be explained by higher androgen levels, but further investigation is required. Similarly, continued research is necessary to optimize a risky decision-making task for both lines, and thus investigate possible genetic differences in risk acceptance that correlate with differences in alcohol intake. </p>

Despite extensive evidence documenting abnormal hypothalamic-pituitary-adrenal (HPA) axis functioning as a risk factor for the development of depression and other psychiatric disorders, and experimental evidence from acute stress manipulations, the effects of sustained cortisol alterations on clinically relevant cognitive-behavioural and neural processing remain poorly understood. The aim of this thesis was to characterise how non-acute changes in cortisol levels modify behavioural and neural biases implicated in stress-related disorders by following two complementary lines of evidence: firstly, by increasing cortisol via a direct pharmacological intervention; and secondly, by testing the ability of gut microbiota manipulations to alter cortisol reactivity. The first study found that sustained increases in cortisol following 10-day administration of hydrocortisone were associated with altered memory and emotional processing in healthy volunteers. Specifically, participants receiving hydrocortisone showed enhanced recognition of emotional words, while their neutral memory performance was unaffected despite lower parahippocampal and occipital activation during viewing and encoding of neutral pictures. Furthermore, we found that resting-state functional connectivity between limbic-temporal regions of interest (amygdala and hippocampus) and the striatum (head of the caudate), as well as frontal and prelimbic cortices was decreased. In contrast, hippocampal and visual processing during negative facial expressions, and functional connectivity between the amygdala and the brainstem at rest, were increased in the hydrocortisone versus placebo groups. Overall, these findings suggest that non-acute increases in glucocorticoids enhance processing of emotionally salient information in limbic-temporal regions, which may modulate further neural mechanisms of sensory and homeostatic relevance. Enhancements in declarative emotional memory following hydrocortisone also implicate the modulation of amygdalar-hippocampal interactions by cortisol. Conversely, neutral stimulus processing was found to be either reduced or unaffected across a number of cognitive and memory domains. A specific increase for negative processing was further supported by poorer self-reported well-being at the mid-point of the study in participants receiving hydrocortisone. In a separate study exploring the ability of prebiotic supplements to affect cortisol reactivity and emotional processing, a Bimuno-galactooligosaccharide prebiotic was found to reduce the waking cortisol response and increase positive versus negative attentional processing in healthy volunteers. While these effects were not found to be associated, they provide initial promising evidence of the ability to target the HPA axis and emotional processing via the gut microbiota in humans. Overall, this thesis supports the idea that stress-induced physiological changes after prolonged or repeated cortisol exposure are associated with neural and behavioural alterations, which in turn have been crucial in understanding neuropsychological mechanisms underlying psychiatric disease. A better stratification of the effects of sustained HPA axis alterations on psychiatrically relevant cognitive-emotional domains and neural mechanisms thus remains of high priority.

O objetivo deste trabalho foi investigar alterações comportamentais produzidas por etanol (ET) e estresse crônico imprevisível (ECI) em camundongos adolescentes (ADL) e adultos (AD), estudando a participação da enzima nNOS. Em camundongos AD também estudamos a atividade da nNOS via receptor NMDA na sensibilização cruzada entre estresse por imobilização (EI) e ET, utilizando dizocilpina (DZP) como pré-tratamento. Os resultados demonstraram haver sensibilização cruzada entre ECI e ET, tanto nos ADL quanto nos AD. Houve aumento da atividade da nNOS em hipocampo (HP) e córtex frontal (CF) de AD submetidos ao ECI. ET atenuou este efeito. A sensibilização cruzada em ADL aumentou atividade da nNOS em CF. O pré-tratamento com 7-nitroindazol inibiu sensibilização cruzada entre ECI e ET em ADL e AD, sinalizando a participação da nNOS. DZP potencializou sensibilização cruzada entre EI e ET e diminuiu a atividade da nNOS em HP e CF de animais submetidos ao EI. ECI e EI induzem sensibilização comportamental ao ET e nNOS participa na sensibilização cruzada entre ECI/EI e ET. / The objective of this work was to investigate behavioral alterations produced by ethanol (ET) and chronic unpredictable stress (CUS) in adolescent (ADL) and adult (AD) mice, studying the nNOS enzyme activity. In AD mice was also studied the nNOS activity through the NMDA receptor in the cross-sensitization between immobilization stress (IS) and ET, by using dizocilpine (DZP) as a pretreatment. The results demonstrate cross-sensitization between CUS and ET in the ADL and AD mice. There was an increase in the nNOS activity in hippocampus (HP) and frontal cortex (FC) of AD submitted to CUS. This effect was attenuated by ET. The cross-sensitization in ADL increased the nNOS activity in FC. The 7-nitroindazole pretreatment inhibit cross-sensitization between CUS and ET in ADL and AD, signaling the nNOS participation. DZP potentiates cross-sensitization between IS and ET and decreased the nNOS activity in HP and FC of animals submitted to IS. CUS and IS induce behavioral sensitization to the ET and nNOS participate in the cross-sensitization between CUS/IS and ET.

Dans son analyse de la démarche de socialisation des enfants, Émile Durkheim met en garde contre « toute action positive destinée à imprimer une orientation déterminée à l’esprit de la jeunesse ». Notre thèse explore les déclinaisons contemporaines de ces « actions positives » qui émanent de l’État et de différents éléments de la société, et qui, en modifiant le fonctionnement cérébral, entendent orienter le comportement d’enfants non malades vers davantage d’attention et moins d’impulsivité. Cette orientation recouvre un enjeu politique : la réduction des inégalités dans les capacités cérébrales, qui tendent à devenir des inégalités majeures dans la société de performance contemporaine. Notre objet de recherche est constitué par les nouveaux pouvoirs exercés par les adultes sur les enfants, au moyen de techniques biomédicales nouvelles, en particulier par des substances chimiques : les médicaments psychostimulants. Les moyens biomédicaux s’exercent directement sur le fonctionnement cérébral, de manière intrusive, sans la médiation du langage et de la communication, et posent de ce fait des nouvelles questions liées à leur puissance d’action. Ce travail se donne pour objectif de contribuer à une théorie de la justice cognitive pour les enfants. Les nouvelles significations des inégalités d’attention dans les apprentissages, les enjeux sociaux de ces inégalités dans une société de performance et les nouvelles possibilités d’intervention biomédicales sur le fonctionnement cérébral des enfants convergent vers de nouvelles formes dans l’économie psychique des enfants. Il semble possible d’interpréter ces nouvelles forces à l’œuvre comme s’inspirant d’un principe de justice. Le débat autour d’une justice cognitive reflète alors le caractère ressenti comme insupportable socialement des inégalités d’attention et le caractère ressenti comme inévitable de la réponse pharmacologique qui lui est associée. Le recours à la théorie d’une justice cognitive implique, pour l’analyse des pratiques de prescription massives de Ritaline, de se situer au-delà du paradigme habituel de contrôle social et de contrôle des comportements par la médicalisation de la société. / The analysis of children’s socialization process made by Emile Durkheim warns us against any actions intended to have an impact on the orientation of the young spirits. Our thesis explores the contemporary range of these positive actions issued from the state as well as from different parts of society. Those ones, by modifying the proper cerebral functioning, are guiding the behaviour of non-ill toward more attention and less impulsivness. This subject has a significant political concern: the reduction of cerebral inequal capacities which tend to become more and more important in our contemporary performance oriented society. Our research investigates new powers exerciced by adults on children, through the use of modern biomedical techniques, and particuly through psychostimulant pharmaceuticals. Biomedical tools directly reach the functioning brain, in an intrusive way, without the intermediate of either language or communication, which therefore arises new questions about their power of action. The aim of this study is to contribute to a theory of a cognitive justice for children. The new meanings of the inequalities of focus in learning, the social issues of these inequalities in a performance society and the new possibilities of biomedical intervention on the functioning brain converge towards new forms in psychic economy of children. It seems possible to interpret those new forces in action through a principle of justice. The debate around a cognitive justice reflects the unbearable social aspect of the disparities in attention capacity and the hypothetically unavoidable pharmacological answers associated to it. The solution of the theory of cognitive justice involves, for the pratical analysis of the massive instruction of Ritaline, to be situated beyond the usual paradigm of social control and behavioural control through society’s medicalization.

Thesis (M.A.)--University of North Carolina at Wilmington, 2003. / Includes bibliographical references (leaves : [84]-89).

No description available.

Five experiments were carried out to discover whether there is a subjective enhancement of temporal contours analogous to the Mach band effects in spatial vision. A transient overshoot in the incremental threshold occurred immediately after the crest of rising linear ramps at photopic levels. A psychophysical matching experiment verified that this peaking effect is perceived as a bright pulse and can be considered the temporal equivalent of the bright Mach band. No equivalent of the dark Mach band at the foot of rising linear ramps was found. Rather there was an anticipatory decrease of sensitivity (Crawford effect) at the base of ascending gradients. The magnitude of this effect was directly proportional to the rate of change of the stimulus at photopic levels. Data from descending ramps was less simple to interpret. A small rise in incremental threshold was sometimes observed at the crest of ramps, but this effect was much less pronounced than the peak at the crest of equivalent ascending ramps. Matching procedures located troughs at the foot of descending ramps which correspond to the dark spatial Mach band. This effect was less apparent when incremental threshold techniques were employed. An experiment using exponential rather than linear change in luminance over time gave results in general accord with the above. The Crawford effect was found to follow the Bunsen-Roscoe Law. It was found that the transient undershoot and overshoot effects were related to the rate of change rather than the actual form of the ramp when the rate of change was greater than about 300mL per second. Impulse responses were derived by differentiating step responses. Ascending steps generated a biphasic impulse response and descending steps give a triphasic unit impulse response. This lack of equivalence over conditions is diagnostic of system nonlinearity. Fourier analysis of the impulse responses showed equivalent spectral components and lowpass filter action in each case, indicating change in gain and phasing rather than time constants occur between 'on' and 'off' conditions. The system was shown to be quasilinear within conditions since linear convolution of the impulse responses with appropriate ramps generated functions that were a fair approximation to the psychophysical response to such ramps. The relationship between the impulse response and the spatial equivalent line spread function was discussed and the similarity of the impulse responses to dynamic changes in sensitivity inferred from results of masking experiments pointed out. The results were then considered in relation to a multichannel model for processing spatiotemporal information.

Five experiments were carried out to discover whether there is a subjective enhancement of temporal contours analogous to the Mach band effects in spatial vision. A transient overshoot in the incremental threshold occurred immediately after the crest of rising linear ramps at photopic levels. A psychophysical matching experiment verified that this peaking effect is perceived as a bright pulse and can be considered the temporal equivalent of the bright Mach band. No equivalent of the dark Mach band at the foot of rising linear ramps was found. Rather there was an anticipatory decrease of sensitivity (Crawford effect) at the base of ascending gradients. The magnitude of this effect was directly proportional to the rate of change of the stimulus at photopic levels. Data from descending ramps was less simple to interpret. A small rise in incremental threshold was sometimes observed at the crest of ramps, but this effect was much less pronounced than the peak at the crest of equivalent ascending ramps. Matching procedures located troughs at the foot of descending ramps which correspond to the dark spatial Mach band. This effect was less apparent when incremental threshold techniques were employed. An experiment using exponential rather than linear change in luminance over time gave results in general accord with the above. The Crawford effect was found to follow the Bunsen-Roscoe Law. It was found that the transient undershoot and overshoot effects were related to the rate of change rather than the actual form of the ramp when the rate of change was greater than about 300mL per second. Impulse responses were derived by differentiating step responses. Ascending steps generated a biphasic impulse response and descending steps give a triphasic unit impulse response. This lack of equivalence over conditions is diagnostic of system nonlinearity. Fourier analysis of the impulse responses showed equivalent spectral components and lowpass filter action in each case, indicating change in gain and phasing rather than time constants occur between 'on' and 'off' conditions. The system was shown to be quasilinear within conditions since linear convolution of the impulse responses with appropriate ramps generated functions that were a fair approximation to the psychophysical response to such ramps. The relationship between the impulse response and the spatial equivalent line spread function was discussed and the similarity of the impulse responses to dynamic changes in sensitivity inferred from results of masking experiments pointed out. The results were then considered in relation to a multichannel model for processing spatiotemporal information.

No description available.