Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique ...and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images MRIs) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer's Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.
Chronic peer victimization has long-term impacts on mental health; however, the biological mediators of this adverse relationship are unknown. We sought to determine whether adolescent brain ...development is involved in mediating the effect of peer victimization on psychopathology. We included participants (n = 682) from the longitudinal IMAGEN study with both peer victimization and neuroimaging data. Latent profile analysis identified groups of adolescents with different experiential patterns of victimization. We then associated the victimization trajectories and brain volume changes with depression, generalized anxiety, and hyperactivity symptoms at age 19. Repeated measures ANOVA revealed time-by-victimization interactions on left putamen volume (F = 4.38, p = 0.037). Changes in left putamen volume were negatively associated with generalized anxiety (t = -2.32, p = 0.020). Notably, peer victimization was indirectly associated with generalized anxiety via decreases in putamen volume (95% CI = 0.004-0.109). This was also true for the left caudate (95% CI = 0.002-0.099). These data suggest that the experience of chronic peer victimization during adolescence might induce psychopathology-relevant deviations from normative brain development. Early peer victimization interventions could prevent such pathological changes.
The growth of white matter during human adolescence shows a striking sexual dimorphism; the volume of white matter increases with age slightly in girls and steeply in boys. Here, we provide evidence ...supporting the role of androgen receptor (AR) in mediating the effect of testosterone on white matter. In a large sample of typically developing adolescents (n = 408, 204 males), we used magnetic resonance imaging and acquired T1-weighted and magnetization transfer ratio (MTR) images. We also measured plasma levels of testosterone and genotyped a functional polymorphism in the AR gene, namely the number of CAG repeats in exon 1 believed to be inversely proportional to the AR transcriptional activity. We found that the testosterone-related increase of white-matter volume was stronger in male adolescents with the lower versus higher number of CAG repeats in the AR gene, with testosterone explaining, respectively, 26 and 8% of variance in the volume. The MTR results suggest that this growth is not related to myelination; the MTR decreased with age in male adolescents. We speculate that testosterone affects axonal caliber rather than the thickness of the myelin sheath.
The neuron doctrine laid the foundation for our current thinking about the structural and functional organization of the human brain. With the basic units of the nervous system—neurons—being ...physically separate, their connectivity relies on the conduction of action potentials in axons and their transmission across the synaptic cleft to the dendrites of other neurons. This study reviews available ex vivo data about the cellular composition of the human cerebral cortex, focusing on axons and dendrites, to conceptualize biological sources of signals detected in vivo with magnetic resonance imaging. To bridge the gap between ex vivo and in vivo observations, I then explain the basic principles of virtual histology, an approach that integrates spatially cell- or process-specific transcriptomic data with magnetic resonance signals to facilitate their neurobiological interpretation. Finally, I provide an overview of the initial insights gained in this manner in studies of brain development and maturation, in both health and disease.
Abstract
Background
The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the ...biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia.
Methods
We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age.
Results
Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen’s d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P < .001). In contrast, participants at risk or in the early stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age.
Conclusions
Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia.
There is increasing evidence that children with autism spectrum disorder (ASD) have age-related differences from controls in cortical volume (CV). It is less clear, however, if these persist in ...adulthood and whether these reflect alterations in cortical thickness (CT) or cortical surface area (SA). Hence, we used magnetic resonance imaging to investigate the relationship between age and CV, CT, and SA in 127 males aged 10 through 60 years (76 with ASD and 51 healthy controls). “Regional” analyses (using cortical parcellation) identified significant age-by-group interactions in both CV and CT (but not SA) in the temporal lobes and within these the fusiform and middle temporal gyri. Spatially nonbiased “vertex-based” analysis replicated these results and identified additional “age-by-group” interactions for CT within superior temporal, inferior and medial frontal, and inferior parietal cortices. Here, CV and CT were 1) significantly negatively correlated with age in controls, but not in ASD, and 2) smaller in ASD than controls in childhood but vice versa in adulthood. Our findings suggest that CV dysmaturation in ASD extends beyond childhood, affects brain regions crucial to social cognition and language, and is driven by CT dysmaturation. This may reflect primary abnormalities in cortical plasticity and/or be secondary to disturbed interactions between individuals with ASD and their environment.
Neurobiology underlying inter-regional variations - across the human cerebral cortex - in measures derived with multi-modal magnetic resonance imaging (MRI) is poorly understood. Here, we ...characterize inter-regional variations in a large number of such measures, including T1 and T2 relaxation times, myelin water fraction (MWF), T1w/T2w ratio, mean diffusivity (MD), fractional anisotropy (FA), magnetization transfer ratio (MTR) and cortical thickness. We then employ a virtual-histology approach and relate these inter-regional profiles to those in cell-specific gene expression. Virtual histology revealed that most MRI-derived measures, including T1, T2 relaxation time, MWF, T1w/T2w ratio, MTR, FA and cortical thickness, are associated with expression profiles of genes specific to CA1 pyramidal cells; these genes are enriched in biological processes related to dendritic arborisation. In addition, T2 relaxation time, MWF and T1w/T2w ratio are associated with oligodendrocyte-specific gene-expression profiles, supporting their use as measures sensitive to intra-cortical myelin. MWF contributes more variance than T1w/T2w ratio to the mean oligodendrocyte expression profile, suggesting greater sensitivity to myelin. These cell-specific MRI associations may help provide a framework for determining which MRI sequences to acquire in studies with specific neurobiological hypotheses.
Previous studies have shown smaller brain volume and less gray matter in children with attention-deficit/hyperactivity disorder (ADHD). Relatively few morphological studies have examined structures ...thought to subserve inhibitory control, one of the diagnostic features of ADHD. We examined one such region, the pars opercularis, predicting a thinner cortex of the inferior frontal gyrus (IFG) in children with ADHD.
Structural images were obtained from 49 children (24 control; 25 ADHD combined subtype) aged 9 though 15 years. Images were processed using a volumetric pipeline to provide a fully automated estimate of regional volumes of gray and white matter. A further analysis using FreeSurfer provided measures of cortical thickness for each lobe, and for 13 regions in the frontal lobe.
Relative to controls, children with ADHD had smaller whole brain volume and lower gray matter, but not white matter, volumes in all lobes. An analysis of frontal regions showed a significant interaction of group by region. Planned contrasts showed bilateral thinner cortex in the pars opercularis in children with ADHD.
Children with ADHD showed both diffuse and regional gray matter abnormalities. Consistent with its putative role in response inhibition, the cortex of the pars opercularis was thinner in children with ADHD who, as expected, had significantly poorer inhibitory performance on a Go/No-go task. These differences held for both hemispheres raising the possibility that a developmental abnormality of IFG might drive development of inhibition difficulties.
Pubertal dynamics plays an important role in physical and psychological development of children and adolescents. We aim to provide reference ranges of plasma testosterone in a large longitudinal ...sample. Furthermore, we describe a measure of testosterone trajectories during adolescence that can be used in future investigations of development.
We carried out longitudinal measurements of plasma testosterone in 2,216 samples obtained from 513 males (9 to 17 years of age) from the Avon Longitudinal Study of Parents and Children. We used integration of a model fitted to each participant's testosterone trajectory to calculate a measure of average exposure to testosterone over adolescence. We pooled these data with corresponding values reported in the literature to provide a reference range of testosterone levels in males between the ages of 6 and 19 years.
The average values of total testosterone in the ALSPAC sample range from 0.82 nmol/L (Standard Deviation SD: 0.09) at 9 years of age to 16.5 (SD: 2.65) nmol/L at 17 years of age; these values are congruent with other reports in the literature. The average exposure to testosterone is associated with different features of testosterone trajectories such as Peak Testosterone Change, Age at Peak Testosterone Change, and Testosterone at 17 years of age as well as the timing of the growth spurt during puberty.
The average exposure to testosterone is a useful measure for future investigations using testosterone trajectories to examine pubertal dynamics.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
White matter occupies almost half of the human brain. It contains axons connecting spatially segregated modules and, as such, it is essential for the smooth flow of information in functional ...networks. Structural maturation of white matter continues during adolescence, as reflected in age-related changes in its volume, as well as in its microstructure. Here I review recent observations obtained with magnetic resonance imaging in typically developing adolescents and point out some of the known variations in structural properties of white matter vis-à-vis brain function in health and disease. I conclude by re-focusing the interpretations of MR-based studies of white matter from myelin to axon.
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