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Rare genomic Copy Number Variants (CNVs) are major contributors to neurodevelopmental disorder. The vast majority of pathogenic CNVs reported back to patients are ultra-rare and their quantitative effects on traits such as intelligence are undocumented. Here, we identified all CNVs ≥ 50 kilobase in 24,092 individuals from unselected and autism cohorts. We developed statistical models to estimate the effect-size of CNVs on intelligence based on their coding and non-coding characteristics. Measures of intolerance to haploinsufficiency best explained the effect of any deletion or duplication on general intelligence. There was no heterogeneity across unselected and autism cohorts. Validation was performed using an intraclass concordance and showed that model estimates of general intelligence were 78% accurate with mean effect-sizes previously published for 47 CNVs. Inheritance data on 27,766 CNVs showed that deletions and duplications with the same large effect-size on intelligence occur de novo at the same frequency. Our first outline for the effect sizes of all coding genes on intelligence suggests that around 10,000 genes affect this trait.

Objective To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline. Methods We assessed 554 community‐dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima–media thickness, velocity, pulsatility, and resistivity indexes) and vertex‐wide cerebral cortical thickness was examined cross‐sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ‐11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function. Results A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ‐11. This association increased in an almost dose–response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = −0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis‐related thinning of the cerebral cortex. Interpretation The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576–587

The neural correlates of human personality have been of longstanding interest; however, most studies in the field have relied on modest sample sizes and few replicable results have been reported to date. We investigated relationships between personality and brain gray matter in a sample of generally healthy, older (mean age 73 years) adults from Scotland drawn from the Lothian Birth Cohort 1936. Participants (N = 578) completed a brain MRI scan and self-reported Big Five personality trait measures. Conscientiousness trait scores were positively related to brain cortical thickness in a range of regions, including bilateral parahippocampal gyrus, bilateral fusiform gyrus, left cingulate gyrus, right medial orbitofrontal cortex, and left dorsomedial prefrontal cortex. These associations – most notably in frontal regions – were modestly-to-moderately attenuated by the inclusion of biomarker variables assessing allostatic load and smoking status. None of the other personality traits showed robust associations with brain cortical thickness, nor did we observe any personality trait associations with cortical surface area and gray matter volume. These findings indicate that brain cortical thickness is associated with conscientiousness, perhaps partly accounted for by allostatic load and smoking status., Highlights • We investigated relationships between personality and neuroanatomy. • Participants (N = 578) completed an MRI scan and Big Five personality trait measures. • Conscientiousness was positively related to cortical thickness in a range of regions. • These included: parahippocampal, fusiform, and cingulate gyri, and frontal cortex. • No other Big Five trait was associated with our brain measures.

Objective: To assess the association between Mediterranean-type diet (MeDi) and change in brain MRI volumetric measures and mean cortical thickness across a 3-year period in older age (73–76 years).\ud \ud Methods: We focused on 2 longitudinal brain volumes (total and gray matter; n = 401 and 398, respectively) plus a longitudinal measurement of cortical thickness (n = 323), for which the previous cross-sectional evidence of an association with the MeDi was strongest. Adherence to the MeDi was calculated from data gathered from a food frequency questionnaire at age 70, 3 years prior to the baseline imaging data collection.\ud \ud Results: In regression models adjusting for relevant demographic and physical health indicators, we found that lower adherence to the MeDi was associated with greater 3-year reduction in total brain volume (explaining 0.5% of variance, p < 0.05). This effect was half the size of the largest covariate effect (i.e., age). Cross-sectional associations between MeDi and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.\ud \ud Conclusions: Lower adherence to the MeDi in an older Scottish cohort is predictive of total brain atrophy over a 3-year interval. Fish and meat consumption does not drive this change, suggesting that other components of the MeDi or, possibly, all of its components in combination are responsible for the association.

Resumen tomado de la publicación Las variaciones de superficie cortical en la corteza dorsolateral prefrontal predicen mejor el futuro desempeño cognitivo que la inteligencia fluida y la memoria operativa. Antecedentes: ¿Predicen las variables cognitivas y biológicas el futuro desempeño cognitivo? Método: en dos grupos independientes de participantes se miden variables cognitivas (inteligencia fluida y cristalizada, memoria operativa y control atencional) y biológicas (grosor y superficie cortical) en dos ocasiones separadas por seis meses, para predecir el desempeño en la tarea n-back valorado doce y dieciocho meses después. Se completan tres etapas: descubrimiento, validación y generalización. En la de descubrimiento se valoran en un grupo de individuos las variables cognitivas/biológicas y el desempeño a predecir. En la de validación, se relacionan las mismas variables con una versión paralela de la n-back completada meses después. En la de generalización, los resultados de la validación se replican en un grupo independiente de individuos. Resultados: las variaciones de superficie cortical en la corteza dorsolateral prefrontal derecha predicen el desempeño cognitivo en los dos grupos independientes de individuos, mientras que las variables cognitivas no contribuyen a la predicción del desempeño futuro. Conclusiones: las diferencias individuales en determinadas variables biológicas predicen el desempeño cognitivo mejor que las variables cognitivas que correlacionan concurrentemente con ese desempeño. Universidad de Oviedo. Biblioteca de Psicología; Plaza Feijoo, s/n.; 33003 Oviedo; Tel. +34985104146; Fax +34985104126; buopsico@uniovi.es ESP

Are cognitive and biological variables useful for predicting future behavioral outcomes? Method: In two independent groups, we measured a set of cognitive (fluid and crystallized intelligence, working memory, and attention control) and biological (cortical thickness and cortical surface area) variables on two occasions separated by six months, to predict behavioral outcomes of interest (performance on an adaptive version of the n-back task) measured twelve and eighteen months later. We followed three stages: discovery, validation, and generalization. In the discovery stage, cognitive/biological variables and the behavioral outcome of interest were assessed in a group of individuals (in-sample). In the validation stage, the cognitive and biological variables were related with a parallel version of the behavioral outcome assessed several months later. In the generalization stage, the validation findings were tested in an independent group of individuals (out-of-sample). Results: The key fi nding revealed that cortical surface area variations within the right dorsolateral prefrontal cortex predict the behavioral outcome of interest in both groups, whereas the cognitive variables failed to show reliable predictive validity. Conclusions: Individual differences in biological variables might predict future behavioral outcomes better than cognitive variables concurrently correlated with these behavioral outcomes, Antecedentes: ¿Predicen las variables cognitivas y biológicas el futuro desempeño cognitivo? Método: en dos grupos independientes de participantes se miden variables cognitivas (inteligencia fluida y cristalizada, memoria operativa y control atencional) y biológicas (grosor y superficie cortical) en dos ocasiones separadas por seis meses, para predecir el desempeño en la tarea n-back valorado doce y dieciocho meses después. Se completan tres etapas: descubrimiento, validación y generalización. En la de descubrimiento se valoran en un grupo de individuos las variables cognitivas/biológicas y el desempeño a predecir. En la de validación, se relacionan las mismas variables con una versión paralela de la n-back completada meses después. En la de generalización, los resultados de la validación se replican en un grupo independiente de individuos. Resultados: las variaciones de superficie cortical en la corteza dorsolateral prefrontal derecha predicen el desempeño cognitivo en los dos grupos independientes de individuos, mientras que las variables cognitivas no contribuyen a la predicción del desempeño futuro. Conclusiones: las diferencias individuales en determinadas variables biológicas predicen el desempeño cognitivo mejor que las variables cognitivas que correlacionan concurrentemente con ese desempeño, This project was supported by PSI2017-82218-P (Ministerio de Economía, Industria y Competitividad, Spain)

Objective:To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the relationship between carotid atheroma and relative cognitive decline. Methods:We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 (LBC1936) who underwent brain MRI and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and IQ at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function. Results:A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = - 0·151, p = 0·001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex. Interpretation:The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence.

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

The radial unit hypothesis provides a framework for global (proliferation) and regional (distribution) expansion of the primate cerebral cortex. Using principal component analysis (PCA), we have identified cortical regions with shared variance in their surface area and cortical thickness, respectively, segmented from magnetic resonance images obtained in 23,800 participants. We then carried out meta-analyses of genome-wide association studies of the first two principal components for each phenotype. For surface area (but not cortical thickness), we have detected strong associations between each of the components and single nucleotide polymorphisms in a number of gene loci. The first (global) component was associated mainly with loci on chromosome 17 (9.5e-32 ≤ p ≤ 2.8e-10), including those detected previously as linked with intracranial volume and/or general cognitive function. The second (regional) component captured shared variation in the surface area of the primary and adjacent secondary visual cortices and showed a robust association with polymorphisms in a locus on chromosome 14 containing Disheveled Associated Activator of Morphogenesis 1 (DAAM1; p=2.4e-34). DAAM1 is a key component in the planar-cell-polarity signaling pathway. In follow-up studies, we have focused on the latter finding and established that: (1) DAAM1 is highly expressed between 12th and 22nd post-conception weeks in the human cerebral cortex; (2) genes co-expressed with DAAM1 in the primary visual cortex are enriched in mitochondria-related pathways; and (3) volume of the lateral geniculate nucleus, which projects to regions of the visual cortex staining for cytochrome oxidase (a mitochondrial enzyme), correlates with the surface area of the visual cortex in major-allele homozygotes but not in carriers of the minor allele. Altogether, we speculate that, in concert with thalamocortical input to cortical subplate, DAAM1 enables migration of neurons to cytochrome-oxidase rich regions of the visual cortex, and, in turn, facilitates regional expansion of this set of cortical regions during development.

Fully characterizing age differences in the brain is a key task for combating aging-related cognitive decline. Using propensity score matching on 2 independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age of 92 years (n = 42) to very similar participants at mean age of 73 years (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in gray and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural aging, in which brains from the 8th and 10th decades of life differ widely despite the same cognitive, socioeconomic, and brain-volumetric starting points.

Fully characterizing age differences in the brain is a key task for combatting ageing-related cognitive decline. Using propensity score matching on two independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age 92 years (n = 42) to very similar participants at mean age 73 (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in grey and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural ageing, in which brains from the eighth and tenth decades of life differ widely despite the same cognitive, socio-economic, and brain-volumetric starting points.

People with larger brains tend to score higher on tests of general intelligence (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comprehensive cognitive test battery. Using structural equation modelling, we related six common magnetic resonance imaging-derived brain variables that represent normal and abnormal features—brain volume, cortical thickness, white matter structure, white matter hyperintensity load, iron deposits, and microbleeds—to g and to fluid intelligence. As expected, brain volume accounted for the largest portion of variance (~ 12%, depending on modelling choices). Adding the additional variables, especially cortical thickness (+~ 5%) and white matter hyperintensity load (+~ 2%), increased the predictive value of the model. Depending on modelling choices, all neuroimaging variables together accounted for 18–21% of the variance in intelligence. These results reveal which structural brain imaging measures relate to g over and above the largest contributor, total brain volume. They raise questions regarding which other neuroimaging measures might account for even more of the variance in intelligence., Highlights • Brain size is known to correlate with general intelligence (g). • It is unclear which other neuroimaging variables contribute beyond total brain size. • We model multiple brain measures and g in a large sample aged around 73 years. • All brain variables together account for around 20% of variance in g.

Part B of the Trail Making Test (TMT-B) is widely used as a quick and easy to administer measure of executive dysfunction. The current study investigated the relationships between TMT-B performance, brain volumes, cortical thickness and white matter water diffusion characteristics in a large sample of older participants, before and after controlling for processing speed. Four hundred and eleven healthy, community-dwelling older adults who were all born in 1936 were assessed on TMT-B, 5 tests of processing speed, and provided contemporaneous structural and diffusion MRI data. Significant relationships were found between slower TMT-B completion times and thinner cortex in the frontal, temporal and inferior parietal regions as well as the Sylvian fissure/insula. Slower TMT-B completion time was also significantly associated with poorer white matter microstructure of the left anterior thalamic radiation, and the right uncinate fasciculus. The majority of these associations were markedly attenuated when additionally controlling for processing speed. These data suggest that individual differences in processing speed contribute to the associations between TMT-B completion time and the grey and white matter structure of older adults.

Objective: To investigate how associations between education and brain structure in older age were affected by adjusting for IQ measured at age 11.\ud \ud Methods: We analyzed years of full-time education and measures from an MRI brain scan at age 73 in 617 community-dwelling adults born in 1936. In addition to average and vertex-wise cortical thickness, we measured total brain atrophy and white matter tract fractional anisotropy. Associations between brain structure and education were tested, covarying for sex and vascular health; a second model also covaried for age 11 IQ.\ud \ud Results: The significant relationship between education and average cortical thickness (β = 0.124, p = 0.004) was reduced by 23% when age 11 IQ was included (β = 0.096, p = 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy.\ud \ud Conclusions: The association between years of education and brain structure ≈60 years later was restricted to cortical thickness in this sample; however, the previously reported associations between longer education and a thicker cortex are likely to be overestimates in terms of both magnitude and distribution. This finding has implications for understanding, and possibly ameliorating, life-course brain health.

Background and Purpose—\ud \ud We assessed cross-sectional and longitudinal relationships between whole brain white matter hyperintensity (WMH) volume and regional cortical thickness.\ud Methods—\ud \ud We measured WMH volume and regional cortical thickness on magnetic resonance imaging at ≈73 and ≈76 years in 351 community-dwelling subjects from the Lothian Birth Cohort 1936. We used multiple linear regression to calculate cross-sectional and longitudinal associations between regional cortical thickness and WMH volume controlling for age, sex, Mini Mental State Examination, education, intelligence quotient at age 11, and vascular risk factors.\ud Results—\ud \ud We found cross-sectional associations between WMH volume and cortical thickness within and surrounding the Sylvian fissure at 73 and 76 years (rho=−0.276, Q=0.004). However, we found no significant longitudinal associations between (1) baseline WMH volume and change in cortical thickness; (2) baseline cortical thickness and change in WMH volume; or (3) change in WMH volume and change in cortical thickness.\ud Conclusions—\ud \ud Our results show that WMH volume and cortical thinning both worsen with age and are associated cross-sectionally within and surrounding the Sylvian fissure. However, changes in WMH volume and cortical thinning from 73 to 76 years are not associated longitudinally in these relatively healthy older subjects. The underlying cause(s) of WMH growth and cortical thinning have yet to be fully determined.

People with larger brains tend to score higher on tests of general cognitive ability (g). It is unclear, however, how much variance in intelligence other brain measurements would account for if included together with brain volume in a multivariable model. We examined a large sample of individuals in their seventies (n = 672) who were administered a comprehensive cognitive test battery. Using structural equation modelling, we related six common magnetic resonance imaging-derived brain variables that represent normal and abnormal features—brain volume, cortical thickness, white matter structure, white matter hyperintensity load, iron deposits, and microbleeds—to g and to ‘fluid’ intelligence. As expected, brain volume accounted for the largest portion of variance (~12%, depending on modeling choices). Adding the additional variables, especially cortical thickness (+~5%) and white matter hyperintensity load (+~2%), increased the predictive value of the model. Depending on modelling choices, all neuroimaging variables together accounted for 18-21% of the variance in intelligence. These results reveal which structural brain imaging measures relate to g over and above the largest contributor, total brain volume. They raise questions regarding which other neuroimaging measures might account for even more of the variance in intelligence.

Malgré l’engouement pour les neurosciences cognitives des émotions et les nombreuses publications des dernières décennies tentant d’élucider les bases neurobiologiques des émotions, nos connaissances sur le domaine restent embryonnaires. Plusieurs questions importantes restent toujours sans réponses incluant s’il existe ou non un système unique pour le traitement de stimuli émotionnels et s’il y a ou non des différences entre les hommes et les femmes pour le traitement de stimuli émotionnels. L’objectif de cette thèse est d’apporter certains éléments de réponses à ces questions à travers une caractérisation du substrat neurobiologique impliqué dans le traitement de stimuli émotionnels visuels et dynamiques. Ce travail a été mené via l’imagerie par résonance magnétique fonctionnelle (IRMf) cérébrale. Le premier chapitre, subdivisé en quatre sections, permet de présenter la perspective dans laquelle s’inscrit la thèse. La première section de ce chapitre sert à établir certaines balises définitionnelles liées aux émotions. La seconde section, basée sur une lecture des textes originaux, retrace les faits historiques saillants de la neurobiologie des émotions allant de Charles Darwin à Joseph Ledoux. La troisième section débute où la seconde s’arrête et continue l’histoire de la neurobiologie des émotions à travers un résumé de toutes les principales méta-analyses d’imagerie fonctionnelle cérébrale des émotions. La dernière section du chapitre permet de présenter la problématique de recherche. La recherche, à proprement parler, qui constitue le corps de la thèse est ensuite présentée sous forme de trois articles. Enfin, les résultats de cette recherche et la manière dont ils s’inscrivent dans la continuité de nos connaissances actuelles font l’objet d’une discussion générale. Le premier article (chapitre II) rapporte, chez les hommes et les femmes, les régions du cerveau qui sont plus activées lors du traitement de films érotiques que lors du traitement de films dits ‘neutres’. Un chevauchement manifeste est observé entre les hommes et les femmes. Par contre, une activation significativement plus grande est observée chez les hommes pour l’hypothalamus, une région importante pour le comportement sexuel à travers la phylogénie. De plus, chez les hommes seulement, l’activation hypothalamique est corrélée à l’excitation sexuelle subjective. Comme la recherche présentée dans le premier article se sert de conditions expérimentales relativement longues pour l’IRMf (i.e. extraits de films de 3 minutes) et que ceci peut induire une nette diminution de signal en lien avec certaines contraintes de l’IRMf, le second article (chapitre III) examine les corrélats du traitement de stimuli sexuels en utilisant, cette fois, un paradigme d’IRMf classique où plusieurs extraits de films de 33 secondes sont présentés à la place. Cette étude démontre que, pour le traitement de stimuli sexuels, ce paradigme classique d’IRMf est beaucoup plus sensible que celui du premier article. De plus, comme ce paradigme mène à une reproduction des résultats du premier papier, ce travail soutient la perspective selon laquelle les paradigmes à époques courtes sont une alternative valide aux longues époques comme méthode d’étude du traitement de stimuli émotionnels. Le troisième article (chapitre IV) capitalise sur le protocole du second article et démontre que les patrons d’activation associés au visionnement de courts extraits de films induisant du dégoût, de l’amusement, ou de l’excitation sexuelle, sont très étendus. Une analyse de conjonction formelle démontre un large chevauchent de ces patrons à travers les différents affects étudiés. Enfin, le cinquième chapitre sert de discussion générale. Les questions des différences entre les hommes et les femmes dans le traitement des émotions, de l’existence ou non d’un système général pour le traitement des émotions, ainsi que de la manière dont un tel système pourrait être conçu, sont des points saillants de la discussion. Ces points sont abordés à la lumières des connaissances actuelles et des résultats des trois articles., Despite the intense interest garnered by cognitive neurosciences of emotions and the numerous publications in recent decades attempting to partial the neurobiological basis of emotions, our knowledge of the area remains embryonic. Important questions that need to be answered include whether or not there exists a general system for processing emotional stimuli and whether or not there are differences between men and women in processing emotional stimuli. The main objective of this dissertation is to provide some answers to these questions by characterizing the neurobiological substrate involved in processing dynamic visual emotional stimuli. This work was conducted through cerebral functional magnetic resonance imaging (fMRI). The first chapter, which is divided into four sections, lays the groundwork for the thesis. The first section of this chapter serves to clarify some definitional background related to emotions. The second section, based on a reading of the original texts, traces the salient historical facts of the neurobiology of emotions from Charles Darwin to Joseph Ledoux. The third section begins where the second ends and continues the history of the neurobiology of emotions through a summary of all the main functional brain imaging meta-analyzes of emotions. The final section of the chapter introduces the research problematic. The research itself, which constitutes the body of the dissertation, is then presented in the form of three articles. Finally, results of this research and how they fit into the continuity of our current knowledge form the basis of a general discussion. The first paper (Chapter II) reports, in men and women, the brain regions that are more activated during the processing of erotic film excerpts than during the processing of so-called 'neutral' film excerpts. A clear overlap is observed between men and women. This being said, a significantly greater activation is observed in men for the hypothalamus, a region important for sexual behavior across the phylogeny. In addition, in men only, hypothalamic activation is correlated with reported sexual arousal. As the research presented in the first paper uses relatively long experimental conditions for fMRI (i.e. 3-minute film excerpts) and as this can lead to a net signal decrease due to certain fMRI constraints, the second paper (Chapter III) examines correlates of processing sexual stimuli using, this time, a classic fMRI paradigm where several short film clips of 33 seconds are used instead. This study shows that, for the processing of sexual stimuli, this conventional fMRI paradigm is much more sensitive than the one used in the first paper. Importantly, given that this paradigm leads to a reproduction of results of the first paper, this work supports the view that short epochs are a valid alternative to long epochs as a method of studying the processing of emotional stimuli. The third section (Chapter IV) capitalizes on the protocol of the second paper and demonstrates that the activation patterns associated with the viewing of short film excerpts inducing disgust, amusement, or sexual arousal, are extensive. A formal conjunction analysis shows a broad overlap of these patterns across the various affects studied. Finally, the fifth chapter provides a general discussion of the results. The question of gender differences in processing emotional stimuli, of whether or not a general system for processing emotions exists, and of how it may be understood, represent important elements of the discussion. These points are discussed in light of current knowledge and of the results of the three papers.

The relationship between anxious/depressed traits and neuromaturation remains largely unstudied. Characterizing this relationship during healthy neurodevelopment is critical to understanding processes associated with the emergence of child/adolescent onset mood/anxiety disorders. In this study, mixed-effects models were used to determine longitudinal cortical thickness correlates of Child Behavior Checklist (CBCL) and Young Adult Self Report Anxious/Depressed scores in healthy children. Analyses included 341 subjects from 4.9 to 22.3 year-old with repeated MRI at up to 3 time points, at 2-year intervals (586 MRI scans). There was a significant “CBCL Anxious/Depressed by Age” interaction on cortical thickness in the right ventromedial prefrontal cortex (vmPFC), including the medial orbito-frontal, gyrus rectus, and subgenual anterior cingulate areas. Anxious/Depressed scores were negatively associated with thickness at younger ages (

Neuroimaging studies provide evidence for organized intrinsic activity under task-free conditions. This activity serves functionally relevant brain systems supporting cognition. Here, we analyze changes in resting-state functional connectivity after videogame practice applying a test–retest design. Twenty young females were selected from a group of 100 participants tested on four standardized cognitive ability tests. The practice and control groups were carefully matched on their ability scores. The practice group played during two sessions per week across 4 weeks (16 h total) under strict supervision in the laboratory, showing systematic performance improvements in the game. A group independent component analysis (GICA) applying multisession temporal concatenation on test–retest resting-state fMRI, jointly with a dual-regression approach, was computed. Supporting the main hypothesis, the key finding reveals an increased correlated activity during rest in certain predefined resting state networks (albeit using uncorrected statistics) attributable to practice with the cognitively demanding tasks of the videogame. Observed changes were mainly concentrated on parietofrontal networks involved in heterogeneous cognitive functions.