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This research work aimed to find out whether there is correlation between continuous assessment (CA) scores and national form four final examination results in Tanzania 2021/2022 in Morogoro Municipality. The specific objectives were to assess the correlation between CA scores and form four final examination results basing in Biology, Chemistry, Physics, Mathematics and English Language. The study used Ex post facto research design because it groups the qualities that already exist and compared on some dependent variables. This study preferred this design because it has an ability to use the information that has been grouped based on a particular characteristics or trait. The study also used purposive sampling technique to select the two government secondary schools in Morogoro Municipality as well as five subjects which were taken as a sample these are Biology, Physics, Chemistry, Mathematics and English language following the low performance to most of the candidates to the mentioned subjects above. The data were collected by using documentary instrument where the head of schools had given the Mock results of 2021which were caped as CA documents due to the fact that mock is regarded as a reflection of the NECTA results since it is always done after undergoing several number of assessments to the candidates where mock becomes the almost last measure of the candidates to attempt the national form four examination and national form four results 2021/2022 were taken from the NECTA website. The data were analyzed using Pearson’s product moment correlation coefficient (r) and the null hypotheses were tested at 0.05 level of significance. The findings that from five subjects that is Biology, Chemistry, Physics, Mathematics and English language. There were positive correlation between CA scores and NECTA results 2021/2022 because the significance level was .000 then in Biology (r) = .845, Physics r = .773, Chemistry r = .886, Mathematics r = .715 and English language r = .849 respectively. So they rejected null hypothesis and accept alternative hypothesis. This indicated that there was positive correlation between CA scores and national form four final examination results.

Oxycodone is the one of the most common opioids utilized worldwide to treat patients with moderate to severe pain while also potentially possessing molecules that can influence a protein which plays a crucial role in expressing synaptic activity. The aim is to analyze the impact of Oxycodone on levels of serum Brain-derived neurotrophic (BDNF). To ultimately attain reliable BDNF levels measured in serum, monoclonal antibodies and a sandwich ELISA will be utilized along with a population of 300 volunteers. Volunteers who suffer from severe chronic pain will be selected in the age range of 18 to 24. Based upon existing literature involving the examination of BDNF levels, these levels can generally be accurately assessed and dependably measured in human serum over one year which should be enough to identify significant differences in serum.

Objective: The aim of this study was to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the Fatigue Severity Scale (FSS, preplanned primary outcome), another fatigue measure, sleep quality, somnolence, pain, disability, and quality of life in multiple sclerosis (MS) patients with obstructive sleep apnea-hypopnea (OSAH). Methods: In a randomized, double-blind trial (NCT01746342), MS patients with fatigue, poor subjective sleep quality, and OSAH (apnea-hypopnea index of ⩾ 15 events per hour/sleep), but without severe OSAH (apnea-hypopnea index > 30, and 4% oxygen desaturation index > 15 events/hour or severe somnolence), were randomized to fixed CPAP or sham CPAP for 6 months. Outcome assessments were performed at 3 and 6 months. Results: Of 49 randomized patients, 34 completed the protocol. Among completers, FSS did not improve with CPAP compared to sham at 6 months. FSS tended to improve ( p = 0.09), and sleepiness (Epworth Sleepiness Scale) improved significantly ( p = 0.03) at 3 months with CPAP compared to sham, but there were no other improvements with CPAP at either study evaluation. Conclusion: In non-severe OSAH patients, CPAP did not significantly improve the primary outcome of FSS change at 6 months. In secondary analyses, we found a trend to improved FSS, and a significant reduction in somnolence with CPAP at 3 months.

The paper uses Kane&rsquo, s formalism to study two degrees of freedom (DOF) mechanisms with elastic elements = employed in a wind water pump. This formalism represents an alternative, in our opinion, that is simpler and more economical to Lagrange&rsquo, s equation, used mainly by researchers in this type of application. In the problems where the finite element method (FEM) is applied, Kane&rsquo, s equations were not used at all. The automated computation causes it to be reconsidered in the case of mechanical systems with a high DOF. Analyzing the planar transmission mechanism, these equations were applied for the study of an elastic element. An analysis was then made of the results obtained for this type of water pump. The matrices coefficients of the obtained equations were symmetric or skew-symmetric.

Life-long maintenance of brain health is important for the prevention of cognitive impairment in older age. Low-grade peripheral inflammation associated with excess visceral fat (VF) may influence brain structure and function. Here we examined (i) if this type of inflammation is associated with altered white-matter (WM) microstructure and lower cognitive functioning in adolescents, and (ii) if recently identified circulating glycerophosphocholines (GPCs) can index this type of inflammation and associated variations in WM microstructure and cognitive functioning. We studied a community-based sample of 872 adolescents (12–18 years, 48% males) in whom we assessed VF and WM microstructure with magnetic resonance imaging, processing speed with cognitive testing, serum C-reactive protein (CRP, a common marker of peripheral inflammation) with a high-sensitivity assay, and serum levels of a panel of 64 GPCs with advanced mass spectrometry. VF was associated with CRP, and CRP in turn was associated with “altered” WM microstructure and lower processing speed (all p

Neurobiological underpinnings of cortical thickness in the human brain are largely unknown. Here we use cell-type-specific gene markers to evaluate the contribution of 9 neural cell-types in explaining inter-regional variations in cortical thickness and age-related cortical thinning in the adolescent brain. Gene-expression data were derived from the Allen Human Brain Atlas (and validated using the BrainSpan Atlas). Values of cortical thickness/thinning were obtained with magnetic resonance imaging in a sample of 987 adolescents. We show that inter-regional profiles in cortical thickness relate to those in the expression of genes marking CA1 pyramidal cells, astrocytes, and microglia; taken together, the 3 cell types explain 70% of regional variation in cortical thickness. We also show that inter-regional profiles in cortical thinning relate to those in the expression of genes marking CA1 and S1 pyramidal cells, astrocytes and microglia. Using Gene Ontology analysis, we demonstrate that the difference in the contribution of CA1 and S1 pyramidal cells may relate to biological processes such as neuronal plasticity and potassium channel activity, respectively. This "virtual histology" approach (scripts provided) can be used to examine neurobiological underpinnings of cortical profiles associated with development, aging, and various disorders.

Background: Parkinson’s disease (PD) is the second most frequent neurodegenerative disease and is associated with cognitive dysfunction. Obstructive sleep apnea (OSA) has been linked with cognitive dysfunction in the general population and in PD. Treatment with positive airway pressure (PAP), can improve cognition in the general population and in patients with other neurodegenerative diseases. However, the effect of PAP therapy on cognitive function has not been well studied in PD.Methods: This randomized controlled trial will assess the effect of 6 months of PAP therapy versus placebo on global cognitive function in PD patients with OSA and reduced baseline cognition. Secondary outcomes will include quality of life and other non-motor symptoms of PD. Exploratory outcomes will be specific domains of neurocognitive function and symptoms of REM sleep behaviour disorder.Conclusions: PD-related cognitive dysfunction often evolves towards dementia and has substantial personal, social and healthcare costs. Few interventions have been shown to improve cognition in PD to date. If positive, results from our study could prove OSA to be a new therapeutic target relevant to cognition and would support more systematic screening for OSA in PD patients with cognitive decline.Trial Registration: Trial registration number is NCT02209363.

Background: Glycerophosphocholine (GPC) metabolites modulate atherosclerosis and thus risk for cardiovascular disease (CVD). Preclinical CVD may start during adolescence. Here, we used targeted serum lipidomics to identify a new panel of GPCs, and tested whether any of these GPCs are associated, in adolescence, with classical risk factors of CVD, namely excess visceral fat (VF), elevated blood pressure, insulin resistance, and atherogenic dyslipidemia. Methods: We studied a population-based sample of 990 adolescents (12–18 years, 48% male), as part of the Saguenay Youth Study. Using liquid chromatography-electrospray ionization-mass spectrometry, we identified 69 serum GPCs within the 450 to 680 m / z range. We measured VF with MRI. Results: We identified several novel GPCs that were associated with multiple CVD risk factors. Most significantly, PC16:0/2:0 was negatively associated with VF ( P =1.4×10 –19 ), blood pressure ( P =7.7×10 –5 ), and fasting triacylglycerols ( P =9.0×10 –5 ), and PC14:1/0:0 was positively associated with VF ( P =3.0×10 –7 ), fasting insulin ( P =5.4×10 –32 ), and triacylglycerols ( P =1.4×10 –29 ). The Sobel test of mediation revealed that both GPCs mediated their respective relations between VF (as a potential primary exposure) and CVD risk factors (as outcomes, P values–3 ). Furthermore, a GPC shown recently to predict incident coronary heart disease in older adults, PC18:2/0:0, was associated with several CVD risk factors in adolescents; these associations were less strong than those with the newly identified GPCs. Conclusions: We identified novel GPCs strongly associated with multiple CVD risk factors in adolescents. These GPCs may be sensitive indicators of obesity-related risk for CVD outcomes in adults, and may improve biological understanding of CVD risk.

Our ability to process complex social cues presented by faces improves during adolescence. Using multivariate analyses of neuroimaging data collected longitudinally from a sample of 38 adolescents (17 males) when they were 10, 11.5, 13 and 15 years old, we tested the possibility that there exists parallel variations in the structural and functional development of neural systems supporting face processing. By combining measures of task-related functional connectivity and brain morphology, we reveal that both the structural covariance and functional connectivity among ‘distal’ nodes of the face-processing network engaged by ambiguous faces increase during this age range. Furthermore, we show that the trajectory of increasing functional connectivity between the distal nodes occurs in tandem with the development of their structural covariance. This demonstrates a tight coupling between functional and structural maturation within the face-processing network. Finally, we demonstrate that increased functional connectivity is associated with age-related improvements of face-processing performance, particularly in females. We suggest that our findings reflect greater integration among distal elements of the neural systems supporting the processing of facial expressions. This, in turn, might facilitate an enhanced extraction of social information from faces during a time when greater importance is placed on social interactions.

This study examined cognitive predictors of sequential motor skills in 215 children with dyslexia and/or attention deficit/hyperactivity disorder (ADHD). Visual working memory and math fluency abilities contributed significantly to performance of sequential motor abilities in children with dyslexia (N = 67), ADHD (N = 66) and those with a comorbid diagnosis (N = 82), generally without differentiation between groups. In addition, primary diagnostic features of each disorder, such as reading and inattention, did not contribute to the variance in motor skill performance of these children. The results support a unifying framework of motor impairment in children with neurodevelopmental disorders such as dyslexia and ADHD.

SummaryBackground Excess visceral fat is a major risk factor for hypertension. Enhanced blood pressure (BP) reactivity and delayed BP recovery from physical and mental challenges predict future hypertension. Objectives Determine whether visceral fat is associated with higher BP reactivity and delayed BP recovery from physical and mental challenges during adolescence. Methods In a community-based sample of 283 male and 308 female adolescents, we measured visceral fat with magnetic resonance imaging, total body fat with bioimpedance, and beat-by-beat BP with a Finometer at rest and during physical (10-min standing) and mental (2-min math stress) challenges. Results Males vs. females showed greater BP reactivity and no differences in BP recovery from either type of challenges. Visceral fat was positively associated with BP reactivity to standing up only and in males only (+8.4 ± 3.6 mmHg per 1 log cm3 of visceral fat, P = 0.008), and this association was independent of total body fat. No association was seen between visceral fat and BP recovery from either type of challenge in either sex. All these associations were independent of age, puberty stage, height and initial BP. Conclusions Adolescent males vs. females demonstrate greater BP reactivity but similar BP recovery from physical and mental challenges. Excess visceral fat enhances BP reactivity to physical but not mental challenges in males only.

Hypertension is a leading cause of death. Sex differences in blood pressure (BP) and hypertension prevalence emerge during adolescence and remain throughout reproductive age. Sex differences in BP-underlying hemodynamics, i.e., in the relative contributions of stroke volume (SV), total peripheral resistance (TPR) and heart rate (HR) to BP, have not been investigated in these age categories in a population-based setting. We studied a cohort of 1,347 individuals, including 911 adolescents (12-18 years, 52 % female) and 426 young to middle-aged adults (36-65 years, 56 % female). Beat-by-beat systolic BP (SBP) and diastolic BP (DBP), together with HR, SV, and TPR, were measured with a Finometer throughout a 52-min protocol; the protocol was intended to “mimic” daily-life activities, such as changes in posture and mental stress. It is well established that BP during regular daily activities (ambulatory BP monitoring) is a better predictor of target-organ damage than standard office BP. The relative contributions of HR, SV and TPR to SBP and DBP were determined by decomposing the model-explained variance into non-negative contributions. The relative contributions of SV, TPR and HR to SBP and DBP showed marked sex differences in young and middle-aged adults. The main determinant of higher SBP was SV in females (55 [50-60] % in females vs. only 35 [30-40] % in males), whereas it was TPR in males (47 [41-52] % in males vs. only 30 [26-34] % in females). The main determinant of higher DBP was TPR in both sexes, but its contribution was higher in males than females (58 [52-63] % vs. 41 [36-45] %, respectively). These sex differences were seen across most of the 52-min protocol, being most prominent during standing and least evident during mental stress. Similar sex differences were observed in adolescents, but they were less pronounced, being significant only during standing. The present population-based study of adolescents and young to middle-aged adults, suggest that marked sex differences exist in BP-underlying hemodynamics, with BP being driven mainly by SV in females and by TPR in males. These results underscore the need for sex-specific treatments of hypertension (not recommended currently), which affects 3-5 % of adolescents and 23-58% of young to middle-aged adults.

Income inequality is associated with poor health and social outcomes. Negative social comparisons and competition may involve the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes in underlying some of these complex inter-relationships. Here we investigate brain maturation, indexed by age-related decreases in cortical thickness, in adolescents living in neighborhoods with differing levels of income inequality and household income. We examine whether inter-regional variations relate to those in glucocorticoid receptor (HPA) and androgen receptor (HPG) gene expression. For each sex, we used a median split of income inequality and household income (income-to-needs ratio) to create four subgroups. In female adolescents, the high-inequality low-income group displayed the greatest age-related decreases in cortical thickness. In this group, expression of glucocorticoid and androgen receptor genes explained the most variance in these age-related decreases in thickness across the cortex. We speculate that female adolescents living in high-inequality neighborhoods and low-income households may experience greater HPA and HPG activity, leading to steeper decreases in cortical thickness with age.

Contains fulltext : 169834.pdf (Publisher’s version ) (Open Access) Contains fulltext : 169834pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0.0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0.15), amygdala (d=-0.19), caudate (d=-0.11), hippocampus (d=-0.11), putamen (d=-0.14), and intracranial volume (d=-0.10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0.95) and thalamus (p=0.39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (21 years): in the accumbens (Cohen's d=-0.19 vs -0.10), amygdala (d=-0.18 vs -0.14), caudate (d=-0.13 vs -0.07), hippocampus (d=-0.12 vs -0.06), putamen (d=-0.18 vs -0.08), and intracranial volume (d=-0.14 vs 0.01). There was no difference between children and adults for the pallidum (p=0.79) or thalamus (p=0.89). Case-control differences in adults were non-significant (all p>0.03). Psychostimulant medication use (all p>0.15) or symptom scores (all p>0.02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0.5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health. 10 p.

We used magnetic resonance (MR) images obtained in same-sex and opposite-sex dizygotic twins (n = 119, 8 years of age) to study possible effects of prenatal androgens on craniofacial features. Using a principal component analysis of 19 craniofacial landmarks placed on the MR images, we identified a principal component capturing craniofacial features that distinguished females with a presumed differential exposure to prenatal androgens by virtue of having a male (vs. a female) co-twin (Cohen's d = 0.76). Subsequently, we tested the possibility that this craniofacial "signature" of prenatal exposure to androgens predicts brain size, a known sexually dimorphic trait. In an independent sample of female adolescents (singletons; n = 462), we found that the facial signature predicts up to 8% of variance in brain size. These findings are consistent with the organizational effects of androgens on brain development and suggest that the facial signature derived in this study could complement other indirect measures of prenatal exposure to androgens.

Author(s): Lotfipour, Shahrdad; Lotfipour, Shahrdad; Ferguson, Eamonn; Leonard, Gabriel; Miettunen, Jouko; Perron, Michel; Pike, G Bruce; Richer, Louis; Seguin, Jean R; Veillette, Suzanne; Jarvelin, Marjo-Riitta; Moilanen, Irma; Maki, Pirjo; Nordstrom, Tanja; Pausova, Zdenka; Veijola, Juha; Paus, Tomas | Abstract: Background and aimsPrenatal exposure to maternal cigarette smoking (PEMCS) is associated with a higher probability of substance use in adolescence. We explore if externalizing behavior mediates this relationship, while controlling for a number of potential covariates of this mediation process.MethodsWe used data obtained in two geographically distinct community samples of adolescents. The first (cross-sectional) sample consisted of 996 adolescents (12-18 years of age) recruited from the Saguenay Youth Study (SYS) in Canada (47% with PEMCS). The second (longitudinal) sample consisted of 1141 adolescents (49% with PEMCS) from the Northern Finland Birth Cohort (NFBC1986). In both samples, externalizing behavior and substance use were assessed during adolescence. In the NFBC1986 cohort, externalizing behavior was also assessed in childhood.ResultsIn both populations, PEMCS is associated with a higher likelihood of adolescent drug experimentation. In the NFBC1986 cohort, exposed (versus non-exposed) adolescents experiment with an extra 1.27 [B = 0.24, 95% confidence intervals (CI) = 0.15, 0.33 P l 0.001] drugs. In the SYS cohort, a clear protective effect of not being exposed is shown: non-exposed (versus exposed) adolescents are 1.5 times [B = -0.42, 95% CI = -0.75, -0.09, P = 0.013] less likely to take drugs. These associations between PEMCS and drug experimentation remain in the multivariate and mediational analyses.ConclusionsPrenatal exposure to maternal cigarette smoking appears to be associated with a higher probability of experimenting with drugs during adolescence, both directly and indirectly via externalizing behavior and the number of peers reported as using drugs.

Background Obesity, a major risk factor for cardiometabolic disease, is associated with lower cognitive performance from childhood to senescence, especially on tasks of executive function. In the cardiovascular domain, fat stored viscerally rather than elsewhere in the body carries particularly high risk. It is unknown whether this is also true in case of obesity-cognition relationships. The aim of this study is to assess the cross-sectional relationship between visceral fat (VF) and cognitive performance in a community sample of healthy adolescents. Methods In a community-based sample of 983 adolescents (12–18 years old, 480 males), VF was quantified using magnetic resonance imaging, total body fat was measured using a multifrequency bioimpedance and cognitive performance was assessed using a battery of cognitive tests measuring executive function and memory. Results We found that larger volumes of VF were associated with lower performance on six measures of executive function (p=0.0001 to 0.02). We also found that the association of VF with executive function was moderated by sex for a subset of measures, such that relationship was present mainly in females and not in males (sex-by-VF interaction: p=0.001 to 0.04). These relationships were independent of the quantity of total body fat and a number of potential confounders, including age, puberty stage and household income. Conclusions Our results suggest that the adverse association between obesity and executive function may be attributed to fat stored viscerally and not to fat stored elsewhere in the body. They also suggest that females compared with males may be more sensitive to the potentially detrimental effects of VF on cognition.

BackgroundMultiple sclerosis (MS) patients have central nervous system (CNS) lesions that may impede cognitive and sensorimotor function. Few rehabilitative therapies are available.ObjectivesThe objective of this paper is to study effects of noninvasive tongue stimulation using the Portable Neuromodulation Stimulator (PoNS™) combined with intensive cognitive and physical rehabilitation on working memory, gait, balance and concomitant changes in the brain.MethodsFourteen MS patients, seven each in an active and a sham stimulation group, participated. Participants received intensive physical therapy and working memory training for 14 weeks. Functional magnetic resonance imaging (fMRI) using motor imagery and working-memory tasks were completed prior to and following therapy, as were sensory organization tests (SOT), motor performance measures, and neuropsychological assessment.ResultsOn the SOT, the active group showed significant improvement from baseline. fMRI revealed significant blood oxygen level-dependent signal changes in the left primary motor cortex for the Active Group, while the sham group had increased activity in bilateral premotor cortices. All individuals improved on working-memory tasks, but only the active group showed increased dorsolateral prefrontal cortex activity.ConclusionsIn this cohort of MS patients, the results suggest that PoNS stimulation can enhance motor performance and working memory while also driving neuroplasticity. Further studies are warranted to explore these findings.

Age-related decreases in cortical thickness observed during adolescence may be related to fluctuations in sex and stress hormones. We examine this possibility by relating inter-regional variations in age-related cortical thinning (data from the Saguenay Youth Study) to inter-regional variations in expression levels of relevant genes (data from the Allen Human Brain Atlas); we focus on genes coding for glucocorticoid receptor (NR3C1), androgen receptor (AR), progesterone receptor (PGR), and estrogen receptors (ESR1 and ESR2). Across 34 cortical regions (Desikan-Killiany parcellation), age-related cortical thinning varied as a function of mRNA expression levels of NR3C1 in males (R(2) = 0.46) and females (R(2) = 0.30) and AR in males only (R(2) = 0.25). Cortical thinning did not vary as a function of expression levels of PGR, ESR1, or ESR2 in either sex; this might be due to the observed low consistency of expression profiles of these 3 genes across donors. Inter-regional levels of the NR3C1 and AR expression interacted with each other vis-à-vis cortical thinning: age-related cortical thinning varied as a function of NR3C1 mRNA expression in brain regions with low (males: R(2) = 0.64; females: R(2) = 0.58) but not high (males: R(2) = 0.0045; females: R(2) = 0.15) levels of AR mRNA expression. These results suggest that glucocorticoid and androgen receptors contribute to cortical maturation during adolescence.

The Saguenay Youth Study (SYS) is a two-generational study of adolescents and their parents (n = 1029 adolescents and 962 parents) aimed at investigating the aetiology, early stages and trans-generational trajectories of common cardiometabolic and brain diseases. The ultimate goal of this study is to identify effective means for increasing healthy life expectancy. The cohort was recruited from the genetic founder population of the Saguenay Lac St Jean region of Quebec, Canada. The participants underwent extensive (15-h) phenotyping, including an hour-long recording of beat-by-beat blood pressure, magnetic resonance imaging of the brain and abdomen, and serum lipidomic profiling with LC-ESI-MS. All participants have been genome-wide genotyped (with ∼ 8 M imputed single nucleotide polymorphisms) and a subset of them (144 adolescents and their 288 parents) has been genome-wide epityped (whole blood DNA, Infinium HumanMethylation450K BeadChip). These assessments are complemented by a detailed evaluation of each participant in a number of domains, including cognition, mental health and substance use, diet, physical activity and sleep, and family environment. The data collection took place during 2003-12 in adolescents (full) and their parents (partial), and during 2012-15 in parents (full). All data are available upon request.

Adults show great variation in their auditory skills, such as being able to discriminate between foreign speech-sounds. Previous research has demonstrated that structural features of auditory cortex can predict auditory abilities; here we are interested in the maturation of 2-Hz frequency-modulation (FM) detection, a task thought to tap into mechanisms underlying language abilities. We hypothesized that an individual's FM threshold will correlate with gray-matter density in left Heschl's gyrus, and that this function-structure relationship will change through adolescence. To test this hypothesis, we collected anatomical magnetic resonance imaging data from participants who were tested and scanned at three time points: at 10, 11.5 and 13 years of age. Participants judged which of two tones contained FM; the modulation depth was adjusted using an adaptive staircase procedure and their threshold was calculated based on the geometric mean of the last eight reversals. Using voxel-based morphometry, we found that FM threshold was significantly correlated with gray-matter density in left Heschl's gyrus at the age of 10 years, but that this correlation weakened with age. While there were no differences between girls and boys at Times 1 and 2, at Time 3 there was a relationship between gray-matter density in left Heschl's gyrus in boys but not in girls. Taken together, our results confirm that the structure of the auditory cortex can predict temporal processing abilities, namely that gray-matter density in left Heschl's gyrus can predict 2-Hz FM detection threshold. This ability is dependent on the processing of sounds changing over time, a skill believed necessary for speech processing. We tested this assumption and found that FM threshold significantly correlated with spelling abilities at Time 1, but that this correlation was found only in boys. This correlation decreased at Time 2, and at Time 3 we found a significant correlation between reading and FM threshold, but again, only in boys. We examined the sex differences in both the imaging and behavioral data taking into account pubertal stages, and found that the correlation between FM threshold and spelling was strongest pre-pubertally, and the correlation between FM threshold and gray-matter density in left Heschl's gyrus was strongest mid-pubertally.

Excess body fat deposited viscerally rather than elsewhere in the body is associated with higher risk for hypertension; this relationship is stronger in men than in women. Here we investigated whether similar sex dimorphism exists already in adolescence. A population-based sample of adolescent boys (n=237) and girls (n=262), age 12 to 18 years, was studied. Total body fat (TBF) was assessed with multifrequency bioelectrical impedance, and visceral fat (VF) was quantified with MRI. Blood pressure (BP) was measured beat by beat during an hour-long protocol, including supine, standing, sitting, mental stress, and poststress sections. Multivariate mixed-model analysis was used to assess the relative contributions of TBF and VF to BP during these sections. In boys, BP was strongly positively associated with VF ( P P =0.004); these relationships did not substantially vary during the protocol. In contrast, in girls, BP was strongly positively associated with TBF ( P =0.0006), whereas it was not associated with VF ( P =0.08); the relationship with TBF varied during the protocol and was most apparent during mental stress (TBF*section interaction: P =0.002). Furthermore, when waist circumference was included in multivariate models instead of VF, it was not associated with BP in either sex; this indicates that waist circumference may not be an appropriate surrogate for VF. Thus, in adolescence, adiposity-related BP elevation is driven mainly by visceral fat in males and by fat deposited elsewhere in females. This dimorphism suggests sex-specific mechanisms of obesity-induced hypertension and the need for sex-specific criteria of its prevention.

Hypertension, typically considered a disorder of adulthood, is now emerging in adolescence. This is mainly due to the growing prevalence of obesity and the fact that excess body fat increases blood pressure (BP).The objective of the study was to investigate whether genome-wide identified gene loci of obesity are associated with elevated BP in adolescence.This was a genotype-phenotype association study.The study was conducted in a French-Canadian founder population.Participants included 598 adolescents, aged 12-18 yr.Testing associations between 530,011 single-nucleotide polymorphisms (SNP; Human610W-Quad BeadChip) and obesity measures and between identified SNP and BP.Total fat mass (TFM) was assessed with bioelectrical impedance, and body mass index (BMI) was determined with anthropometry. BP was measured beat by beat during an hour-long protocol.The genome-wide association studies of TFM and BMI revealed two novel and several previously identified loci of obesity. The former were PAX5 (rs16933812, TFM: P = 9.3 × 10(-9)) and MRPS22 (rs7638110, BMI: P = 4.6 × 10(-8)), and the top ones among the latter (P5 × 10(-4)) were MC4R (rs17773430, BMI: P = 5.8 × 10(-6)), FTO (rs9930333, BMI: P = 1.9 × 10(-4)), and MTCH2 (rs7120548, BMI: P = 1.9 × 10(-4)). From these five, only the PAX5, MRPS22, and FTO were also associated with BP; their minor allele homozygotes vs. major allele homozygotes showed greater TFM by 2.9-8.0 kg and higher BP by 3.3-6.7 mm Hg.Genome-wide association studies conducted in an adolescent founder population revealed two new and a number of previously identified loci of obesity and demonstrated that several but not all of these loci are also associated with elevated BP. These results begin to reveal the genetic architecture of obesity-induced hypertension.

Successful interpersonal interactions rely on an ability to read the emotional states of others and to modulate one's own behavior in response. The actions of others serve as valuable social stimuli in this respect, offering the observer an insight into the actor's emotional state. Social cognition continues to mature throughout adolescence. Here we assess longitudinally the development of functional connectivity during early adolescence within two neural networks implicated in social cognition: one network of brain regions consistently engaged during action observation and another one associated with mentalizing. Using fMRI, we reveal a greater recruitment of the social–emotional network during the observation of angry hand actions in male relative to female adolescents. These findings are discussed in terms of known sex differences in adolescent social behavior.

Sex identification of a face is essential for social cognition. Still, perceptual cues indicating the sex of a face, and mechanisms underlying their development, remain poorly understood. Previously, our group described objective age- and sex-related differences in faces of healthy male and female adolescents (12-18 years of age), as derived from magnetic resonance images (MRIs) of the adolescents' heads. In this study, we presented these adolescent faces to 60 female raters to determine which facial features most reliably predicted subjective sex identification. Identification accuracy correlated highly with specific MRI-derived facial features (e.g. broader forehead, chin, jaw, and nose). Facial features that most reliably cued male identity were associated with plasma levels of testosterone (above and beyond age). Perceptible sex differences in face shape are thus associated with specific facial features whose emergence may be, in part, driven by testosterone.

This study investigated the fine-grained development of the EEG power spectra in early adolescence, and the extent to which it is reflected in changes in peak frequency. It also sought to determine whether sex differences in the EEG power spectra reflect differential patterns of maturation. A group of 56 adolescents were tested at age 10 years and then at two further time-points approximately 18 months apart. The EEG was recorded during both eyes-closed and eyes-open conditions and Fourier transformed to provide estimates of absolute and relative spectral power at 0.5 Hz intervals from 0.5 to 40 Hz. The peak alpha frequency for each individual at each time-point was also determined for relative spectral power. Partial Least Squares (PLS) analysis was used to determine the combination of electrodes and frequencies that showed developmental change, or differed between the sexes. As a function of age, absolute delta and theta frequencies power decreased, and relative alpha2 and beta frequencies increased, replicating the standard findings of a decrease in lower, and increase in higher, frequencies with age. A small but significant increase in peak alpha frequency with age was detected. Moreover PLS analysis performed with individual alpha frequencies aligned to 10 Hz suggested that the age-related increase seen in alpha2 relative power was driven by changes in the peak frequency. Although males demonstrated higher alpha power than females, there were no sex differences in peak frequency, suggesting that there may be more to sex differences in EEG power than simply different rates of maturation between the two sexes.

Adolescence places high demands on inter-personal interactions and, hence, on the extraction and processing of social cues. Here we assess longitudinally the development of brain activity within a network implicated in social cognition--the action observation network. We performed activation likelihood estimation meta-analyses to define regions of interest based upon the mature action observation network of adults. Using functional magnetic resonance imaging, we then examined developmental trajectories of functional brain activity within these brain regions. Using this approach, we reveal quadratic trajectories within a fronto-parietal network previously shown to demonstrate correlated morphological development.

In industrialized countries, prenatal exposure to maternal cigarette smoking (PEMCS) is the most common environmental insult to the fetus. Here, we tested the hypothesis that PEMCS amplifies accumulation of abdominal fat during the accelerated weight gain occurring in late puberty. This hypothesis was tested in 508 adolescents (12-18 years, 237 exposed prenatally to maternal cigarette smoking) in whom subcutaneous and intra-abdominal fat were quantified with magnetic resonance imaging (MRI). We found that, in early puberty, exposed and nonexposed adolescents did not differ in MRI-based measures of adiposity. In late puberty, on the other hand, exposed compared with nonexposed adolescents demonstrated markedly higher quantities of both subcutaneous fat (by 26%, P = 0.004) and intra-abdominal fat (by 33%, P = 0.001). These group differences remained virtually unchanged after adjusting for sex and potential confounders, including birth weight and breastfeeding. As such, our results suggest that PEMCS may represent a major risk factor for the development of abdominal obesity at the later stages of puberty.

Intra-abdominal accumulation of fat is a hallmark of male body-fat distribution and a major risk factor for hypertension. Sympathoactivation may be one of the mechanisms linking intra-abdominal obesity to hypertension. The aim of the present study was to investigate whether a functional variation in the androgen-receptor gene ( AR , a variable number of CAG repeats in exon 1) is associated with intra-abdominal adiposity, sympathetic modulation of vasomotor tone, and blood pressure in adolescent boys but not girls. We studied 223 boys and 259 girls (age 12 to 18 years) from a French-Canadian founder population. Intra-abdominal fat and subcutaneous-abdominal fat were quantified with an MRI. Blood pressure was recorded beat-to-beat during an hour-long protocol including physical and mental challenges, and these blood pressure time series were used to assess sympathetic modulation of vasomotor tone by power spectral analysis. The results showed that boys with a “low” versus “intermediate” or “high” CAG-repeat number in AR demonstrated higher intra-abdominal fat (by 28% and 48%, respectively) but not subcutaneous-abdominal fat. These intra-abdominal fat differences remained significant after adjusting for serum levels of sex hormones and subcutaneous-abdominal fat. Furthermore, boys with low versus intermediate or high CAG-repeat numbers also showed higher blood pressure, with the differences being most pronounced during mental stress (8.0 and 8.5 mm Hg, respectively) and higher sympathetic modulation of vasomotor tone. As expected, no such differences were seen among girls. In adolescent boys, low CAG-repeat numbers in AR may be a genetic risk factor for intra-abdominal obesity and hypertension; sympathoactivation may be an underlying link between the 2 conditions.

Here we examined sex differences in the volumes of grey and white matter, and in grey-matter "density," in a group of typically developing adolescents participating in the Saguenay Youth Study (n=419; 12-18 years). In male adolescents, we also investigated the role of a functional polymorphism in androgen-receptor gene (AR) in moderating the effect of testosterone on volumes of grey and white matter and grey-matter density. Overall, both absolute and relative volumes of white matter were larger in male vs. females adolescents. The relative grey-matter volumes were slightly larger in female than male adolescents and so was the grey-matter density in a large number of cortical regions. In male adolescents, functional polymorphism of AR moderated the effect of testosterone on relative white- and grey-matter volumes. Following a discussion of several methodological and interpretational issues, we outline future directions in investigating brain-behavior relationships vis-à-vis psychopathology.

With anatomical magnetic resonance imaging, the signal intensity of the corticospinal tract (CST) at the level of the internal capsule is often paradoxically similar to that of grey matter. As shown previously in histological studies, this is likely due to the presence of very large axons. We measured the apparent grey‐matter density (aGMd) of the putative CST (pCST) in a large cohort of adolescents (n = 409, aged 12–18 years). We tested the following hypotheses: (1) The aGMd in the pCST shows a hemispheric asymmetry that is, in turn, related to hand preference; (2) the maturation of the CST during adolescence differs between both sexes, due to the influence of testosterone; (3) variations in aGMd in the pCST reflect inter‐individual differences in manual skills. We confirmed the first two predictions. Thus, we found a strong left > right hemispheric asymmetry in aGMd that was, on average, less marked in the 40 left‐handed subjects. Apparent GMd in the pCST increased with age in adolescent males but not females, and this was particularly related to rising plasma levels of testosterone in male adolescents. This finding is compatible with the idea that testosterone influences axonal calibre rather than myelination. The third prediction, namely that of a relationship between age‐related changes in manual skills and maturation of the pCST, was not confirmed. We conclude that the leftward asymmetry of the pCST may reflect an early established asymmetry in the number of large corticomotoneuronal fibres in the pCST. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.

Background— FTO is the first gene established as contributing to common forms of obesity. The gene is highly expressed in the hypothalamus and is thought to mediate this effect through its influence on energy homeostasis. The hypothalamus, however, also regulates blood pressure (BP). Therefore, we investigated whether the FTO -risk variant is associated not only with increased adiposity but also with elevated BP and whether the latter may be mediated, in part, by increased sympathetic modulation of vasomotor tone. Methods and Results— The primary study was carried out in 485 adolescents recruited from a French Canadian founder population who underwent detailed body-composition and cardiovascular phenotyping. Body fat was examined with MRI, bioimpedance, and anthropometry. BP was recorded beat to beat at rest and during physical and mental challenges. Sympathetic modulation of vasomotor tone was assessed with power spectral analysis of BP. We found that individuals with the FTO- risk genotype compared with those without it demonstrate greater adiposity, including the amount of intra-abdominal fat (by 38%). They also showed higher systolic BP throughout the entire protocol, with a maximum difference during a mental stress (6.4 [1.5 to 11.3] mm Hg). The difference in BP was accompanied by elevated index of sympathetic modulation of vasomotor tone. A replication in an independent sample of adults from the same founder population confirmed the association between FTO and BP. Conclusions— These results suggest that, in a French Canadian founder population, FTO may increase not only risk for obesity, as demonstrated in other populations, but also for hypertension. The latter may be related, at least in part, to the regulation of sympathetic vasomotor tone.

The purpose of this study was to examine sex differences in the maturation of white matter during adolescence (12 to 18 years of age). We measured lobular volumes of white matter and white-matter “density” throughout the brain using T1-weighted images, and estimated the myelination index using magnetisation-transfer ratio (MTR). In male adolescents, we observed age-related increases in white-matter lobular volumes accompanied by decreases in the lobular values of white-matter MTR. White-matter density in the putative cortico-spinal tract (pCST) decreased with age. In female adolescents, on the other hand, we found only small age-related increase in white-matter volumes and no age-related changes in white-matter MTR, with the exception of the frontal lobe where MTR increased. White-matter density in the pCST also increased with age. These results suggest that sex-specific mechanisms may underlie the growth of white matter during adolescence. We speculate that these mechanisms involve primarily age-related increases in axonal calibre in males and increased myelination in females.

Teratogens, such as alcohol or anti-epileptic drugs, affect the size of the corpus callosum. Here we report findings obtained in a case-control study that investigated possible effects of teratogens contained in cigarette smoke on the size and structural properties of this structure. We recruited and scanned with magnetic resonance imaging a total of 408 adolescents (12 to 18 years of age); a subsample of 300 adolescents is considered in this report. Cases (n=146) were exposed to maternal cigarette smoking during pregnancy; non-exposed controls (n=154) were matched to cases by maternal education. We measured the size of corpus callosum (CC) and its sections (corrected for brain size), as well as mean values of magnetization-transfer ratio (MTR) in each CC section. Corpus callosum, and especially its posterior part, was smaller in the exposed vs. non-exposed female adolescents; no significant effects were found in males. Exposed and non-exposed subjects did not differ in the MTR-based index of myelination in either gender in any CC section. Given the lack of exposure effect on the myelination index, this finding might reflect a lower number of inter-hemispheric connections in female offspring of mothers who smoked during pregnancy.

During the shift from a parent-dependent child to a fully autonomous adult, peers take on a significant role in shaping the adolescent's behavior. Peer-derived influences are not always positive, however. Here, we explore neural correlates of interindividual differences in the probability of resisting peer influence in early adolescence. Using functional magnetic resonance imaging, we found striking differences between 10-year-old children with high and low resistance to peer influence in their brain activity during observation of angry hand movements and angry facial expressions: compared with subjects with low resistance to peer influence, individuals with high resistance showed a highly coordinated brain activity in neural systems underlying perception of action and decision making. These findings suggest that the probability of resisting peer influence depends on neural interactions during observation of emotion-laden actions.

Circulating second-messenger glycerophosphocholines (smGPCs), including lysophosphatidylcholines and platelet-activating factors, are low-abundance plasma phospholipids that modulate atherosclerosis and inflammation and, in turn, the risk for cardiovascular disease (CVD). Although CVD is a slow-progressing disease culminating in middle-to-late adulthood, its initial stages may be seen already in adolescence. Here, we investigated whether circulating smGPCs are associated with classical CVD risk factors - excess body fat, elevated BP, insulin resistance and low-grade inflammation - during adolescence. We studied a population-based sample of 1029 adolescents (52% females, 12-18 years), as part of the Saguenay Youth Study. We used targeted serum lipidomics (LC-ESI-MS) to identify and quantify circulating smGPCs within the 440-640 Da range. In all participants, we also measured: (i) visceral fat with MRI and total body fat with bioimpedance; (ii) blood pressure (BP) beat-by-beat for five minutes under standard clinical conditions; and (iii and iv) fasting serum insulin (as an index of insulin resistance) and CRP (as an index of low-grade inflammation). We identified a total of 81 smGPCs that varied by the length and saturation of their fatty acyl residues and the type of linkage these residues are attached to the glycerol backbone. Over 30 of them were associated with multiple CVD risk factors (p-4 ). Most of these associations were inverse and involved ‘medium’ mass smGPCs. Positive associations were also seen and these involved ‘low’ or ‘high’ mass smGPCs. Most strongly inversely associated smGPCs were: (i) PC(20:6/0:0) and PC(O-18:6/2:0), which were associated with total body fat (p-14 ) and CRP (p-36 ); and (ii) PC(16:0/2:0), which was associated with visceral fat (p=2x10 -18 ) and BP (p-5 ). The most strongly positively associated smGPC was PC(14:1/0:0), which was associated with visceral fat (p=8x10 -8 ) and fasting insulin (p=2x10 -24 ). Thus, specific circulating smGPCs are strongly associated with multiple CVD risk factors in adolescence; some of these associations may be ‘protective’ whereas others ‘adverse’. Circulating smGPCs may serve as novel biomarkers of early risk for CVD.

Excess total body fat (TBF) and visceral fat (VF) are major risk factors of hypertension. Blood pressure (BP) increases with age, as do TBF and VF. Here we investigated whether TBF and VF contribute to BP differences between adolescents and adults. A population-based sample of adolescents (n=933, 12-18 years) and their parents (n=429, 38-65 years) was studied as part of the Saguenay Youth Study. In all participants, beat-by-beat values of SBP, DBP and underlying hemodynamic parameters (heart rate, stroke volume [SV] and total peripheral resistance) were obtained with a Finometer during a 52-minute protocol mimicking daily life activities and including posture and math-stress tests. TBF was assessed by bioelectrical impedance and VF was examined by magnetic resonance imaging. SBP was higher in parents than adolescents by an average of 10.2±0.3 mmHg in males and 9.1±0.3 mmHg in females (p

Background/Aims: Visceral fat (VF) compared with subcutaneous fat (SF) is more closely associated with cardiometabolic disease. Dietary vitamin A (retinol) may reduce adiposity through its effects on adipogenesis differentially in VF and SF, and this effect may be modulated by retinol-binding protein-4 (RBP4). We investigated whether intake of vitamin A is associated with either VF or SF, and whether this association is moderated by the RBP4 genotype (rs10882272, C/T) previously associated with circulating retinol levels. Methods: This was a cross-sectional association study in a sample of 947 adolescents from a French-Canadian founder population. VF and SF were quantified with magnetic resonance imaging, and vitamin A intake was assessed with a 24-hour food recall. All participants were genotyped to determine their RBP4 variant. Results: Dietary intake of vitamin A was negatively associated with VF; however, it was not associated with SF. These relationships were independent of age, sex, height and energy intake, and were modulated by the RBP4 variant. The T allele promoted adiposity-reducing effects of vitamin A in VF and adiposity-enhancing effects in SF, while the C allele had adiposity-reducing effects in both VF and SF. Conclusions: Dietary vitamin A may reduce abdominal adiposity and promote visceral to subcutaneous body fat redistribution during adolescence in an RBP4-dependent manner. These observational findings provide the basis for future interventional studies, which together with genetic information may inject further causality in the association between dietary vitamin A intake and abdominal adiposity.