Mutations of three genes encoding amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) have been shown to reliably result in familial early-onset Alzheimer's disease (FAD); a rare, but catastrophic, subtype of Alzheimer's disease (AD) marked by symptom emergence before age 65 as well as accelerated cognitive deterioration. The current study represents the first known meta-analysis on the association of APP, PSEN1 or PSEN2 on neurocognitive variables. A total of 278 FAD mutation-carriers (FAD-MC) and 284 cognitively healthy non-mutation-carriers (NC) across 10 independent investigations meeting inclusion criteria were chosen for the current meta-analysis (random effects design). Findings revealed an overarching trend of poorer performance by FAD-MC individuals compared to NC individuals across the majority of cognitive domains identified. Significant differences in effect sizes suggested FAD-MC individuals exhibited worse performance on measures of attention, explicit memory, fluency, primary memory, verbal, and visuospatial functioning. Findings indicative of differential sensitivity to cognitive domain impairments across FAD-MC and NC groups inform neuropsychological descriptions of individuals in preclinical phases of FAD.

Das menschliche Gehirn ist ein komplexes System, dessen Komplexität von großer funktioneller Bedeutung. Das APOE ɛ4 Allel ist ein gut untersuchter genetischer Risiko-Faktor für die Ausbildung der Alzheimer’schen Demenz. Das wesentliche Ziel dieser Dissertation ist die Untersuchung der Verbindungen zwischen der Komplexität von Hirn-Signalen, APOE-Genotyp und kognitiver Leistung bei jungen gesunden Erwachsenen unter dem Gesichtspunkt individueller Unterschiede. Nachdem ich in der ersten Studie die Reliabilität der Residual Iteration Decomposition (RIDE), einer Methode zur Analyse von Gehirnsignalen, validiert hatte, im der zweiten Studie untersuchte ich, wie APOE-Genotypen mit der Komplexität des Gehirnsignals assoziiert sind, gemessen mit Multiscale Entropy (MSE) und kognitiven Fähigkeiten. Die zweite Studie zeigte, dass APOE ɛ4 mit einer höheren Entropie im Skala 1 bis 4 und einer niedrigeren Entropie im Skala 5 und darüber assoziiert ist; Darüber hinaus gibt es bei ε4-Trägern einen stärkeren Abfall der MSE von geschlossenen zu offenen Augen als bei Nicht-Trägern. Die ε4-Assoziation mit der kognitiven Leistung war komplex, aber im Grunde scheint ε4 mit einer schlechteren kognitiven Leistung bei Menschen mit niedrigerem Bildungsstand verbunden zu sein, während bei Hochschulabsolventen keine solche Assoziation auftrat. Anschließend verband die dritte Studie MSE mit einer anderen kognitiven Domäne - Gesichts- und Objekterkennungsfähigkeiten. Wir haben gezeigt, dass 1) eine erhöhte MSE bei geschlossenen Augen auf allen Skalen mit einer besseren kognitiven Leistung verbunden ist. 2) Eine erhöhte MSE in höheren Skalen war mit einer engeren Kopplung zwischen der RIDE-extrahierten Geschwindigkeit der Bewertung des Stimulus für einen einzelnen Versuch und der Reaktionszeit verbunden. Zusammenfassend, die Ergebnisse verbanden die Komplexität des Gehirnsignals, den APOE-Genotyp und das kognitive Verhalten bieten ein tieferes Verständnis der Gehirn-Verhaltens-Beziehungen. / Human brain is a complex dynamical system, whose complexity could be highly functional and characterize cognitive abilities or mental disorders. The APOE ɛ4 allele is a well-known genetic risk factor for the development of Alzheimer’s Disease and cognitive decline in later human life. The main goal of this study is to investigate the bridges between brain signal complexity, APOE genotype and cognitive performance among young adults under the framework of individual difference. After validating the reliability of Residue Iteration decomposition (RIDE), a method for analysis brain signals in the first study, I investigated in the second study how individual differences in APOE genotypes are associated with brain signal complexity measured with Multiscale Entropy (MSE) and cognitive ability. The second study demonstrated that APOE ε4 is associated with higher entropy at scale 1-4 and lower entropy at scale 5 and above, especially at frontal scalp regions and in an eyes open condition; in addition, there’s a stronger drop in MSE from closed to open eyes condition among ε4 carriers than non-carriers. The ε4 association with cognitive performance was complex, but basically ε4 seems to be associated with worse cognitive performance among lower educated people, whereas no such association appeared among the higher educated. Afterwards, the third study connected MSE with a different cognitive domain – face and object cognition abilities. We showed that 1) increased MSE for a closed eyes condition at all scales is associated with better cognitive performance. 2) Increased MSE at higher scales (7 or 8) was associated with tighter coupling between RIDE-extracted single trial stimulus evaluation speed at the neural level and reaction time at the behavior level. To summarize, the results of my doctoral study connected brain signal complexity, APOE genotype and cognitive behavior among young healthy adults, providing a deeper understanding of brain-behavior relationships and – potentially – for early AD diagnosis when cognitive decline is not yet evident.

The objective of this study was to assess low to high levels of Cognitive Workload by measuring heart rate and cortical blood flow in real-time. Four conditions were implemented into a within-subjects experimental design. Two conditions of difficulty and two conditions of trial order were used to illicit different levels of workload which will be analyzed with psychophysiological equipment. Functional Near-Infrared Spectroscopy (fNIRS) has become more prominent for measuring the blood oxygenation levels in the prefrontal cortex of individuals operating in hazardous work environments, students with learning disabilities, and in research for military training. This is due to the fNIR device being highly mobile, inexpensive, and able to produce a high-spatial resolution of the dorsolateral prefrontal cortex during executive functioning. Heart Rate will be measured by an Electrocardiogram, which will be used in concordance with fNIR oxygenation levels to predict if an individual is in a condition that produces low or high mental workload. Successfully utilizing heart rate and blood oxygenation data as predictors of cognitive workload may validate implementing multiple physiological devices together in real-time and may be a more accurate solution for preventing excessive workload.

Chapter 1: This paper offers new causal evidence on how the timing of prenatal temperature shocks affects fetal health, sex ratio at birth, and early-age human capital. Analyzing data on nearly 2 million live births from sub-Saharan African countries and exploiting exogenous spatial and temporal variation in monthly temperature, we uncover three findings. First, we find that a cold temperature shock decreases the likelihood of a male birth. This effect is non-linear, being larger in the first and third trimesters of pregnancy. It is also highly heterogeneous, being larger for older women, higher parity births, and rural areas. Second, combining our empirical estimates with a climate model, we find that the number of fetal deaths caused by climate change will rise from 200 to 400 per 100,000 live births by 2050 throughout sub-Saharan Africa. Third, in contrast to their differential effect on fetal mortality, prenatal temperature shocks increase infant mortality more for females than for males, suggesting that only healthier male fetuses survive to adverse in utero conditions. Our analysis implies that the design of policies to avert the negative impacts of climate change on children should account for stages of fetal development. Chapter 2: Despite its enormous individual and social costs; the fundamental and long- run causes of cognitive aging remain understudied. We study the causal effect of in-utero temperature exposure on cognition during old age. Combining unique data on South African adults between 40 and 99 years of age with geospatial information on historical temperatures, our identification strategy exploits exogenous, within-municipality-of-birth, month-to-month variations in temperature, and controls for contemporaneous weather and location at the time of survey administration. We find that temperature in the first trimester of pregnancy negatively affects the cognitive function score later in life, but temperature in the second and third trimesters has a positive effect on adults cognitive function score. These differing effects result in an overall U-shaped relationship between prenatal exposure to temperature and cognition. This non-linear relationship is robust across measures of memory, reasoning, and information processing speed. Our findings are consistent with the fetal programming theory, which holds that the first trimester of pregnancy is the most crucial window of brain formation. In accordance with this theory, brain development occurring in the first trimester of pregnancy would therefore have the highest vulnerability to external shocks. Heterogeneity analysis reveals that the effect of prenatal temperature on cognition is larger for men, individuals over 75 years of age, and individuals with low social capital. Analyzing causal mechanisms, we find that prenatal temperature affects key determinants of individuals' cognitive reserve. We also find that exposure to drought during the first trimester of pregnancy and reduced sleep during adulthood are other potential channels through which the effects of prenatal exposure to temperature operate. Chapter 3: A large literature seeking to understand the labor market impacts associated with the clean energy transitions broadly finds opposite effects. On the one hand, a net positive impact on the workforce i.e. the new green jobs created in renewable energy sectors will compensate for the jobs lost in fossil-fuel sectors, while on the other hand, the so-called regulated dirty energy sector will reduce the fraction of workers hired. However, empirical and simulation models typically ignore transitional impacts associated with environmental regulations on labour. These relate to how workers adjust over time to environmental regulations, not just the steady state impact that is the focus of prior studies. We evaluate an environmental regulation (Ontario coal-fired electricity generating plants phase-out) regarding its transitional and long-term impacts on employee's outcomes including (i) wages; (ii) unemployment insurance; (iii) sector mobility; and (iv) geographic location. Using the Longitudinal Worker File (LWF) and Postal Codes Conversion File (PCCF) maintained by Statistics Canada, we estimate the labor market impacts of clean energy policy by comparing employees from affected coal plants to a comparable group of employees from non-affected plants. We find that, workers exposed to Ontario phase-out coal policy have earned on average 7000 $ CAD yearly less compared to those who weren't exposed. Our findings are consistent across a set of alternative specifications and robustness checks. Moreover, results from the event study approach suggest that the regulation leads to labor costs with the de- cline of wages just in transition. We provide supportive evidence on large labor costs due to environmental regulation policy and shed lights on the importance of reforms and training programs to support workers during the transition.

Cette étude s’intéresse au lien entre les dynamiques cérébrales et les capacités cognitives, cette problématique a déjà été explorée auparavant en imagerie cérébrale, notamment à l’aide de tâches effectuées pendant l’imagerie. Cependant la caractérisation de l’activité spontanée a principalement été faite soit avec une faible précision spatiale (capteur EEG/MEG), soit en IRMf qui a une faible résolution temporelle. L’objectif de cette thèse est de caractériser l’activité spontanée au repos au niveau cortical associée à différents processus cognitifs et leur performance. Le second chapitre cherche à établir les corrélats neuronaux de la performance de la mémoire au repos à l’aide des puissances spectrales localisées au niveau des sources corticales. Le troisième chapitre cherche à répliquer les méthodes utilisées dans l’article 1 avec les mêmes participants, mais dans un autre domaine cognitif afin d’établir les corrélats neuronaux de la fluence verbale ainsi que de discriminer une composante verbale et exécutive. Ces deux composantes ont été mises en évidence en utilisant une factorisation avec un test purement exécutif (Trail making test- condition 4) et un autre purement verbal (richesse du vocabulaire). Dans le quatrième chapitre, nous répliquons encore la méthode de l’article 1 avec les mêmes sujets, mais sur un test d’apprentissage verbal. Lors de l’apprentissage verbal, deux stratégies d’apprentissage (sériel et sémantique) possibles sont utilisées de manière concurrente, nous avons cherché à établir si des différences comportementales se traduisaient par des patrons d’activation différents. Dans le cinquième chapitre, nous avons cherché à établir des différences fonctionnelles entre les survivants de la leucémie et des sujets contrôles, puis à établir un lien entre la neurotoxicité et le déficit cognitif rencontré chez cette population, finalement nous avons établi un modèle intégrant neurotoxicité, performance cognitive et marqueur neurophysiologique fonctionnel cérébral. Cette recherche aura approfondi les connaissances sur l’état de repos et principalement fourni les premiers travaux qui mettent en lien l’activité cérébrale spontanée au repos au niveau des sources corticales avec plusieurs tests neuropsychologiques comportementaux. Les résultats ont amené des patrons d’activation spatio-fréquentielle différents, démontrant des spécificités reliées à certains tests comportementaux ou des traitements de l’information (sériel ou sémantique). Finalement les travaux sur les survivants de la leucémie ont montré que l’état de repos pouvait caractériser le fonctionnement des déficits cognitifs à long terme et être un marqueur de remédiation pour de futurs traitements. / This study is interested in the link between brain dynamics and cognitive abilities. This problem has already been explored before in brain imaging, notably with the help of task performed during imaging. However, the characterization of spontaneous activity has mainly been done either with weak spatial resolution (EEG/MEG sensor) or in fMRI which has a low temporal resolution. The objective of this thesis is to characterize the spontaneous activity at rest at the cortical level associated with different cognitive processes and their performance. The second chapter seeks to establish the neural correlates of resting memory performance using spectral powers localized at cortical sources. The third chapter seeks to replicate the methods used in article 1 with the same participants but in another cognitive domain in order to establish the neural correlates of verbal fluency as well as to discriminate a verbal and an executive component. These two components were highlighted using a factorization with a purely executive test (Trail making test-condition 4) and another purely verbal one (vocabulary richness). In the fourth chapter, we replicate the method of article 1 with the same subjects, but on a verbal learning test. During verbal learning, two possible learning strategies (serial and semantic) are used concurrently, we sought to establish whether behavioural differences translate into different activation patterns. In the fifth chapter, we sought to establish functional differences between leukemia survivors and control subjects, then to search for a link between neurotoxicity and the cognitive deficit encountered in this population; finally we established a model integrating neurotoxicity, cognitive performance and functional neurophysiological brain markers. This research will have deepened the knowledge on the resting state and mainly provided the first works that link the spontaneous brain activity at rest at the level of cortical sources with several behavioural neuropsychological tests. The results led to different spatio-frequential activation patterns, showing specificities related to certain behavioural tests or information processing (serial or semantic). Finally, work on leukemia survivors has shown that resting states could characterize the functioning of long-term cognitive deficits and be a remediation marker for future treatments.

No description available.

No description available.

In connection with the world becoming more digitalized, the need for competence within Computer Science and IT has simultaneously increased, in which programming and mathematics are fundamental competences. At the same time digital music and headphones may enable students within these fields of knowledge to regularly listen to their prefered music while studying without disturbing their surroundings. The purpose of this study is to examine if the short-term performance of mathematics and programming is improved by listening to preferred music during examinations. Furthermore, to find out if the results can be explained by the following seven parameters: the perceived achievement, difficulty, focus, working memory, stress, anxiety and motivation. The participants completed tests in math and programming in two music conditions: with preferred study music and in silence. Moreover, they were given surveys concerning the seven parameters and their general relation to music as it regards their studying. The results showed that the participants performed better while listening to music for both math and programming. With an increase of 10.43% for mathematics and 12.47% increase for programming. However, more evidence is needed to conclude the causation. The underlying factors are unclear. While the mean value and the median value for the parameters show minimal differences between the musical conditions, with the exception of the perceived difficulty, it appears that several participants felt that the music aided in blocking surrounding noises and contributed to a better mood and focus. The increase in performance can also have been affected by other factors than the music. / Digitaliseringens framväxt har lett till att efterfrågan och behovet av att utbilda akademiker med kompetens inom datavetenskap och IT har ökat, där programmering och matematik är grundläggande kunskaper. [9] Samtidigt kan digital musik och hörlurar underlätta för studenter inom dessa kompetensområden att regelbundet lyssna på sin favoritmusik under studierna utan att störa omgivningen. Syftet med arbetet är att undersöka om den kortsiktiga prestationen, under examination inom matematik respektive programmering, förbättrades vid musiklyssnande och ifall resultatet kan förklaras med hjälp av sju olika parametrar: deltagarnas upplevda prestation, svårighetsgrad, fokus, arbetsminne, stress, ångest samt motivation. Experimentet gick ut på att låta deltagarna skriva prov inom matematik respektive programmering både med och utan musik, samt svara på enkäter kopplade till de sju parametrarna och deras relation till musiklyssnande under studerandet. Resultaten tyder på att musiklyssnande under testerna förhöjde deltagarnas prestation inom matematik och programmering med en procentuell ökning på 10,43% respektive 12,47%. Dock behövs mer underlag för att konstatera ett orsakssamband. Resultaten för bakomliggande faktorer är otydliga. Medelvärde och median för parametrarna ger inte klara samband varken musiklyssning eller utan. Utöver upplevd svårighetsgrad, så ger de flesta parametrarna minimala skillnader. Deltagarna meddelade att musiken underlättade att filtrera bort bakgrundsljud som kan förbättra fokuset och bidragit med bättre sinnesstämning. Ökningen i prestation kan också ha påverkats av flera andra faktorer än just musiklyssning.

Impairment of cognitive performance is often observed in time-on tasks. Theoretical considerations suggest that especially prefrontal cortex cognitive control functions is affected by time-on-task effects, but the role of effort/task engagement is not understood. We examine time-on-task effects in cognitive control on a neurophysiological level using a working-memory modulated response inhibition task and inter-relate prefrontal neuroanatomical region-specific theta-band activity with pupil diameter data using EEG-beamforming approaches. We show that task performance declines with time-on tasks, which was paralleled by a concomitant decreases of task-evoked superior frontal gyrus theta-band activity and a reduction in phasic pupil diameter modulations. A strong relation between cognitive control-related superior frontal theta-band activity and effort/task engagement indexed by phasic pupil diameter modulations was observed in the beginning of the experiment, especially for tasks requiring inhibitory controls and demanding high working memory. This strong relation vanished at the end of the experiment, suggesting a decoupling of cognitive control resources useable for a task and effort invested that characterizes time-on-task effects in prefrontal cortical structures.

Les athlètes utilisent les suppléments nutritionnels avec pour objectif d'améliorer leur performance sportive. La performance sportive dépend de facteurs physiques, mais également de facteurs cognitifs. Les suppléments nutritionnels riches en flavanols issu du cacao (CF) peuvent stimuler la fonction vasculaire, réduire le stress oxydant et améliorer la fonction cognitive. L'objectif de cette thèse est donc d’analyser les effets d'une consommation aigue, ou pendant une semaine, de CF, sur la performance physique et cognitive chez des athlètes, chez des sujets actifs et chez des personnes ayant un diabète de type 1 (DT1). De plus, l’objectif est d’investiguer les effets des CF en altitude simulé, où l’hypoxie limite la performance cognitive et physique.La consommation aigue de 900 mg CF (dont 196 mg d'épicatéchine) suscite une augmentation de l’oxygénation cérébrale, mais pas de la concentration de BDNF sérique et n'a pas d’effet sur la fonction cognitive chez des sportifs sains. L’effet bénéfique des CF sur l’oxygénation cérébrale au repos est dépassé par l’ampleur de l’augmentation de la perfusion et de l’oxygénation cérébrale à l’exercice physique et n'est donc plus visible en post-exercice.En hypoxie (altitude simulée de 4000 m), la consommation aigue de 530 mg CF (dont 100 mg d'épicatéchine) augmente la réponse hémodynamique du cortex préfrontal durant une tâche cognitive, mais n’affecte pas l’activité neuronale. Les CF améliorent la pensée abstraite en normoxie, mais n’améliorent aucun autre domaine des fonctions cognitives. Seule la précision lors du test de Stroop est diminuée par l’hypoxie. De plus, la réponse hémodynamique du cortex préfrontale et l’activité neuronale ne diffèrent pas en hypoxie vs. en normoxie.Le diabète de type 1 (DT1) est associé avec une dysfonction endothéliale, qui constitue un des facteurs de déclin cognitif lié au diabète. Dans une 3ième étude, la fonction cognitive n’est pas altérée chez les patients DT1, en comparaison des sujets sains, alors que l'activation cérébrale diffère entre ces 2 groupes. Cette différence d'activation cérébrale pourrait alors jouer un rôle compensatoire chez les patients DT1. La consommation aigue de CF peut améliorer les fonctions exécutives chez des patients DT1 et des sujets sains, et peut augmenter le signal BOLD dans les régions du cerveau activées par les tâches cognitives.Ainsi, la consommation aigue de CF augmente la vasoréactivité cérébrale. Ces changements sont associés avec une meilleure fonction cognitive chez des patients DT1, alors que ce n’est pas le cas chez des sujets entraînés, ni au niveau de la mer, ni en hypoxie. Malgré ces effets bénéfiques des CF, l’exercice physique semble rester un moyen beaucoup plus efficace pour stimuler la vasoreactivité cérébrale et les fonctions cognitives.Nous nous sommes aussi intéressés aux effets de CF sur la capacité antioxydante, le stress oxydant et la production de NO pendant l’exercice, ainsi que sur les implications pour la performance physique et la récupération, chez des athlètes. La consommation aigue de 903 mg CF augmente la capacité antioxydante au repos et pendant l’exercice, mais sans réduire le stress oxydant et la production de NO. La consommation pendant une semaine de 530 mg CF (dont 100 mg d'épicatéchine) atténue la peroxydation lipidique induite par l’exercice, mais n’influence pas la capacité antioxydante. Les CF ne modifient pas la production et la biodisponibilité du NO pendant un exercice en normoxie et en hypoxie (altitude simulée de 3000 m). La consommation de CF pendant une semaine peut augmenter la fonction endothéliale de repos, et peut réduire les effets nuisibles de l'hypoxie sur l’oxygénation préfrontale au repos et pendant l’exercice modéré. Par contre, cet effet disparait pendant l’exercice intense. La consommation aigue, et pendant une semaine, de CF n’augmente pas la performance physique, ni en normoxie, ni en hypoxie. / Sports performance depends on physical factors, but also on cognitive functioning. Nutritional supplements as potential ergogenic aids can impact muscle, but also the brain. Cocoa flavanols (CF) have antioxidant capacities, can stimulate vascular function, and potentially enhance cognitive function. CF intake might thus improve exercise performance and recovery by reducing oxidative stress, increasing NO availability and/or boosting cognitive function. It is the purpose of this PhD to identify the effects of CF on physical and cognitive performance in healthy athletes at sea level and altitude, as well as in patients with type 1 diabetes. Our systematic review showed that CF can reduce exercise-induced oxidative stress, but without improving exercise performance. Combining CF intake and exercise training improves cardiovascular risk factors and vascular function in healthy and overweight participants, but evidence on the synergistic effects of CF and exercise training on oxidative stress, inflammation and fat and glucose metabolism is lacking.In a randomized, placebo-controlled, double blind cross-over study, we showed that 900 mg CF intake increased prefrontal oxygenation in athletes, but without affecting executive function. BDNF was not affected by CF intake. The effects of high-intensity exercise largely overruled the effects of CF intake: large beneficial effects of exercise on prefrontal oxygenation and cognitive function were observed and CF supplementation did not enlarge these effects. In a 2nd study, the effect of acute CF intake (530 mg CF) on performance on a demanding cognitive test was assessed in normoxia and hypoxia (simulated altitude 4000 m). Electroencephalogram and fNIRS were used to analyse neuronal activity and hemodynamic changes. Acute CF intake improved the neurovascular response, but did not affect neuronal activity and cognitive performance in normoxia and hypoxia. Most cognitive functions, the cerebrovascular response and neuronal activity, were not altered in hypoxia in healthy subjects. In a 3rd study, we found that acute intake of 900 mg CF enhanced cognitive performance on the Flanker test in patients with type 1 diabetes, and their healthy matched controls. CF intake increased the BOLD response in brain areas activated during this specific task. While cognitive performance was not deteriorated in patients with type 1 diabetes, a different brain activation pattern during the cognitive task was observed, compared to healthy controls and this brain activation pattern was altered by CF intake. To conclude, acute CF intake improves prefrontal oxygenation and cerebrovascular responsiveness. This can be associated with better cognitive function in patients with type 1 diabetes, but does not result in improved executive function in healthy persons. Compared to exercise, the magnitude of the CF-induced neurovascular changes is small.Two studies were conducted examining the effects of CF on exercise-induced oxidative stress, NO availability and its implications for exercise performance, in well-trained cyclists. We found that acute CF (900 mg) improved the exercise-induced increase in total antioxidant capacity, but did not reduce the exercise-induced increase in lipid peroxidation. One week CF intake (530 mg CF) improved vascular function at rest, and prefrontal oxygenation at rest and during low-intensity exercise, but did not influence muscular oxygenation. One week CF intake partially restored the hypoxia-induced decline in prefrontal oxygenation during rest and low-intensity exercise, but not during high-intensity exercise. One week CF intake reduced exercise-induced lipid peroxidation, but did not alter total antioxidant capacity. Both acute and 1-week CF intake did not improve exercise performance and recovery and do not change NO production during exercise (in normoxia and hypoxia) in well-trained athletes.