scholarly journals Probing brain developmental patterns of myelination and associations with psychopathology in youth using gray/white matter contrast

2018 ◽  
Author(s):  
Linn B. Norbom ◽  
Nhat Trung Doan ◽  
Dag Alnæs ◽  
Tobias Kaufmann ◽  
Torgeir Moberget ◽  
...  
Keyword(s):  
Individual Differences ◽  
White Matter ◽  
Cognitive Ability ◽  
Large Population ◽  
Population Based ◽  
Magnetic Resonance Images ◽  
Childhood And Adolescence ◽  
Cognitive Components ◽  
Age Related ◽  
Regional Associations

AbstractBackgroundCerebral myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. Differential myelination between intracortical and subjacent white matter can be approximated using signal intensities in T1-weighted magnetic resonance images (MRI).MethodsTo test the sensitivity of gray/white matter contrast (GWC) to age and individual differences in psychopathology and general cognitive ability in youth (8-23 years), we formed data-driven psychopathology and cognitive components using a large population-based sample, the Philadelphia Neurodevelopmental Cohort (PNC) (n=6487, 52% females). We then tested for associations with regional GWC defined by an independent component analysis (ICA) in a subsample with available MRI data (n=1467, 53% females).ResultsThe analyses revealed a global GWC component, which showed an age-related decrease from late childhood and across adolescence. In addition, we found regional anatomically meaningful components with differential age associations explaining variance beyond the global component. When accounting for age and sex, both higher symptom levels of anxiety or prodromal psychosis and lower cognitive ability were associated with higher GWC in insula and cingulate cortices and with lower GWC in pre- and postcentral cortices. We also found several additional regional associations with anxiety, prodromal psychosis and cognitive ability.ConclusionIndependent modes of GWC variation are sensitive to global and regional brain developmental processes, possibly related to differences between intracortical and subjacent white matter myelination, and individual differences in regional GWC are associated with both mental health and general cognitive functioning.

scholarly journals Detectable chromosome X mosaicism in males is rarely tolerated in peripheral leukocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weiyin Zhou ◽  
Shu-Hong Lin ◽  
Sairah M. Khan ◽  
Meredith Yeager ◽  
Stephen J. Chanock ◽  
...  
Keyword(s):  
X Chromosome ◽  
Gene Dosage ◽  
Large Population ◽  
Population Based ◽  
Chromosome X ◽  
Genotyping Array ◽  
Chromosome Mosaicism ◽  
Age Related ◽  
Leukocyte Function ◽  
Peripheral Leukocytes

AbstractAge-related male Y and female X chromosome mosaicism is commonly observed in large population-based studies. To investigate the frequency of male X chromosome mosaicism, we scanned for deviations in chromosome X genotyping array intensity data in a population-based survey of 196,219 UK Biobank men. We detected 12 (0.006%) men with mosaic chromosome X gains ≥ 2 Mb and found no evidence for mosaic chromosome X loss, a level of detection substantially lower than for autosomes or other sex chromosomes. The rarity of chromosome X mosaicism in males relative to females reflects the importance of chromosome X gene dosage for leukocyte function.

Blood Pressure and White Matter Hyperintensity Volume - A Review of the Relationship and Implications for Stroke Prediction and Prevention

2012 ◽  
Vol 7 (3) ◽  
pp. 174 ◽  
Author(s):  
Royya Modir ◽  
Hannah Gardener ◽  
Clinton B Wright ◽  
◽  
◽  
...  
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
White Matter ◽  
Large Population ◽  
Brain Perfusion ◽  
The Elderly ◽  
Vascular Cognitive Impairment ◽  
Population Based ◽  
White Matter Hyperintensity ◽  
Prediction And Prevention

A heavy burden of white matter hyperintensities (WMH) is a risk factor for stroke and vascular cognitive impairment making it important to understand their pathophysiology, aetiology and clinical implications. Ageing studies suggest a linear relationship between blood pressure (BP) and both WMH and microstructural integrity in normal-appearing white matter and, after age, hypertension is the strongest risk factor for WMH. Numerous large population-based observational studies have reported significant associations between elevated BP and WMH burden, however, the relative importance of systolic versus diastolic BP remains controversial. Limitations of prior studies include the use of only a single measurement of BP and oversimplifying hypertension as a dichotomous variable. Race/ethnic differences in the association between BP and WMH have been suggested, but most studies only included older Caucasians. Antihypertensive treatment has been demonstrated to slow WMH progression, but lowering BP in the elderly may also reduce brain perfusion in those with poor autoregulation. Ongoing trials aim to clarify the effects of BP treatment on WMH progression in multi-ethnic populations and the implications of these findings for stroke prevention require further study.

scholarly journals Birth weight is associated with brain tissue volumes seven decades later, but not with age-associated changes to brain structure

2020 ◽  
Author(s):  
Emily N. W. Wheater ◽  
Susan D. Shenkin ◽  
Susana Muñoz Maniega ◽  
Maria Valdés Hernández ◽  
Joanna M. Wardlaw ◽  
...  
Keyword(s):  
Birth Weight ◽  
White Matter ◽  
Cognitive Ability ◽  
Brain Tissue ◽  
Brain Structure ◽  
Early Life ◽  
Later Life ◽  
Cortical Surface ◽  
Age Related ◽  
Mri Features

AbstractBirth weight, an indicator of fetal growth, is associated with cognitive outcomes in early life and risk of metabolic and cardiovascular disease across the life course. Cognitive ability in early life is predictive of cognitive ability in later life. Brain health in older age, defined by MRI features, is associated with cognitive performance. However, little is known about how variation in normal birth weight impacts on brain structure in later life. In a community dwelling cohort of participants in their early seventies we tested the hypothesis that birthweight is associated with the following MRI features: total brain (TB), grey matter (GM) and normal appearing white matter (NAWM) volumes; whiter matter hyperintensity (WMH) volume; a general factor of fractional anisotropy (gFA) and peak width skeletonised mean diffusivity (PSMD) across the white matter skeleton. We also investigated the associations of birthweight with cortical surface area, volume and thickness. Birthweight was positively associated with TB, GM and NAWM volumes in later life (β ≥ 0.194), and with regional cortical surface area but not gFA, PSMD, WMH volume, or cortical volume or thickness. These positive relationships appear to be explained by larger intracranial volume rather than by age-related tissue atrophy, and are independent of body height and weight in adulthood. This suggests that larger birthweight is linked to increased brain tissue reserve in older life, rather than a resilience to age-related changes in brain structure, such as tissue atrophy or WMH volume.Significance StatementCognitive brain ageing carries a high personal, societal and financial cost and understanding its developmental origins is important for identifying possible preventative strategies. In a sample of older participants from the Lothian Birth Cohort 1936 we were able to explore the neurobiological correlates of birth weight, which is indicative of the fetal experience. We find that higher birth weight is related to larger brain tissue volumes in later life, but does not modify the trajectory of age-related change. This suggests that early life growth confers preserved differentiation, rather than differential preservation with regards to brain reserve. That these effects are detectable into later life indicates that this variable may be valuable biomarker in the epidemiology of ageing.

scholarly journals Time-lagged associations between cognitive and cortical development from childhood to early adulthood

2019 ◽  
Author(s):  
Eduardo Estrada ◽  
ROBERTO COLOM
Keyword(s):  
Cognitive Ability ◽  
Developmental Psychology ◽  
Brain Plasticity ◽  
Meta Analysis ◽  
Brain Regions ◽  
Integration Theory ◽  
Childhood And Adolescence ◽  
Cognitive Changes ◽  
Cortical Structure ◽  
Age Related

[Paper in press. Accepted for publication in Developmental Psychology. Copyright by APA] Throughout childhood and adolescence, humans experience marked changes in cortical structure and cognitive ability. Cortical thickness and surface area, in particular, have been associated with cognitive ability. Here we ask the question: What are the time-related associations between cognitive changes and cortical structure maturation. Identifying a developmental sequence requires multiple measurements of these variables from the same individuals across time. This allows capturing relations among the variables and, thus, finding whether: (a) developmental cognitive changes follow cortical structure maturation, (b) cortical structure maturation follows cognitive changes, or (c) both processes influence each other over time. 430 children and adolescents (age range = 6.01 – 22.28 years) completed the WASI battery and were MRI scanned at three time points separated by ≈ 2 years (mean age t1 = 10.60, SD = 3.58, mean age t2=12.63, SD=3.62, mean age t3=14.49, SD=3.55). Latent Change Score (LCS) models were applied to quantify age-related relationships among the variables of interest. Our results indicate that cortical and cognitive changes related to each other reciprocally. Specifically, the magnitude or rate of the change in each variable at any occasion –and not the previous level– was predictive of later changes. These results were replicated for brain regions selected according to the coordinates identified in the Basten et al.’s (2015) meta-analysis, to the Parieto-Frontal Integration Theory (P-FIT, Jung & Haier, 2007) and to the whole cortex. Potential implications regarding brain plasticity and cognitive enhancement are discussed.

scholarly journals A High Burden of Cerebral white Matter Lesion: Evidences from 9 Asian Cities

2020 ◽  
Author(s):  
Bonnie Yin Ka Lam ◽  
Brian Yiu ◽  
Encarnita Ampil ◽  
Christopher Li-Hsian Chen ◽  
Yustiani Dikot ◽  
...  
Keyword(s):  
Risk Factors ◽  
White Matter ◽  
Cognitive Performance ◽  
Small Vessel Disease ◽  
White Matter Lesion ◽  
Large Population ◽  
Significant Risk ◽  
Cerebral White Matter ◽  
Age Related ◽  
Asian Cities

Abstract Background Age-related white matter lesion (WML) is considered a manifestation of sporadic cerebral small vessel disease and an important pathological substrate for dementia. Asia is notable for its large population with a looming dementia epidemic. Yet, the burden of WML and its associated risk factors across different Asian societies are unknown. Methods Subjects from 9 Asian cities (Bangkok, Bandung, Beijing, Bengaluru, Hong Kong, Kaohsiung, Manila, Seoul, and Singapore) were recruited (n = 5,701) and classified into i) stroke/transient ischemic attack (TIA), ii) Alzheimer’s disease (AD)/mild cognitive impairment (MCI), or iii) control groups. Data on vascular risk factors and cognitive performance were collected. The severity of WML was visually rated on MRI or CT. ResultsThe prevalence of moderate-to-severe WML was the highest in subjects with stroke/TIA (43.3 %). Bandang Indonesia showed the highest prevalence of WML, adjusted for age, sex, education and disease groups. Hypertension and hyperlipidemia were significant risk factors for WML, and WML was negatively associated with MMSE in all groups. ConclusionsWML is highly prevalent in Asia and is associated with increasing age, hypertension, hyperlipidemia and worse cognitive performance. Concerted efforts to prevent WML will alleviate the huge dementia burden in the rapidly aging Asian societies.

scholarly journals Population-Based Tract-To-Region Connectome of the Human Brain and Its Hierarchical Topology

2021 ◽  
Author(s):  
Fang-Cheng Yeh
Keyword(s):  
Individual Differences ◽  
White Matter ◽  
Population Based ◽  
Cortical Region ◽  
White Matter Tract ◽  
Hierarchical Topology ◽  
Information Gap ◽  
Cortical Regions ◽  
Hierarchical Relation ◽  
Population Probability

Abstract Connectome maps region-to-region connectivities but does not inform which white matter pathways form the connections. Here we constructed the first population-based tract-to-region connectome to fill this information gap. The constructed connectome quantifies the population probability of a white matter tract innervating a cortical region. The results show that ~85% of the tract-to-region connectome entries are consistent across individuals, whereas the remaining (~15%) have substantial individual differences requiring individualized mapping. Further hierarchical clustering on cortical regions revealed their parcellations into dorsal, ventral, and limbic networks based on the tract-to-region connective patterns. The clustering results on white matter bundles revealed the connectome-based categorization of fiber bundle systems in the association pathways. This new tract-to-region connectome provides insights into the connective topology between cortical regions and white matter bundles. The derived hierarchical relation further offers a connectome-based categorization of gray matter and white matter structures.

scholarly journals Tract Specificity of Age Effects on Diffusion Tensor Imaging Measures of White Matter Health

2021 ◽  
Vol 13 ◽  
Author(s):  
Stephanie Matijevic ◽  
Lee Ryan
Keyword(s):  
Older Adults ◽  
Diffusion Tensor Imaging ◽  
Individual Differences ◽  
White Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
White Matter Integrity ◽  
White Matter Tracts ◽  
Apoe Ε4 ◽  
Age Related

Well-established literature indicates that older adults have poorer cerebral white matter integrity, as measured through diffusion tensor imaging (DTI). Age differences in DTI have been observed widely across white matter, although some tracts appear more sensitive to the effects of aging than others. Factors like APOE ε4 status and sex may contribute to individual differences in white matter integrity that also selectively impact certain tracts, and could influence DTI changes in aging. The present study explored the degree to which age, APOE ε4, and sex exerted global vs. tract specific effects on DTI metrics in cognitively healthy late middle-aged to older adults. Data from 49 older adults (ages 54–92) at two time-points separated by approximately 2.7 years were collected. DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD), were extracted from nine white matter tracts and global white matter. Results showed that across timepoints, FA and MD increased globally, with no tract-specific changes observed. Baseline age had a global influence on both measures, with increasing age associated with lower FA and higher MD. After controlling for global white matter FA, age additionally predicted FA for the genu, callosum body, inferior fronto-occipital fasciculus (IFOF), and both anterior and posterior cingulum. Females exhibited lower global FA on average compared to males. In contrast, MD was selectively elevated in the anterior cingulum and superior longitudinal fasciculus (SLF), for females compared to males. APOE ε4 status was not predictive of either measure. In summary, these results indicate that age and sex are associated with both global and tract-specific alterations to DTI metrics among a healthy older adult cohort. Older women have poorer white matter integrity compared to older men, perhaps related to menopause-induced metabolic changes. While age-related alterations to white matter integrity are global, there is substantial variation in the degree to which tracts are impacted, possibly as a consequence of tract anatomical variability. The present study highlights the importance of accounting for global sources of variation in DTI metrics when attempting to investigate individual differences (due to age, sex, or other factors) in specific white matter tracts.

scholarly journals Developmental Changes in Dynamic Functional Connectivity From Childhood Into Adolescence

2021 ◽  
Vol 15 ◽  
Author(s):  
Mónica López-Vicente ◽  
Oktay Agcaoglu ◽  
Laura Pérez-Crespo ◽  
Fernando Estévez-López ◽  
José María Heredia-Genestar ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Network Connectivity ◽  
Population Based ◽  
Repeated Measurements ◽  
Developmental Changes ◽  
Childhood And Adolescence ◽  
Dynamic Functional Connectivity ◽  
Age Related ◽  
Dynamic States

The longitudinal study of typical neurodevelopment is key for understanding deviations due to specific factors, such as psychopathology. However, research utilizing repeated measurements remains scarce. Resting-state functional magnetic resonance imaging (MRI) studies have traditionally examined connectivity as ‘static’ during the measurement period. In contrast, dynamic approaches offer a more comprehensive representation of functional connectivity by allowing for different connectivity configurations (time varying connectivity) throughout the scanning session. Our objective was to characterize the longitudinal developmental changes in dynamic functional connectivity in a population-based pediatric sample. Resting-state MRI data were acquired at the ages of 10 (range 8-to-12, n = 3,327) and 14 (range 13-to-15, n = 2,404) years old using a single, study-dedicated 3 Tesla scanner. A fully-automated spatially constrained group-independent component analysis (ICA) was applied to decompose multi-subject resting-state data into functionally homogeneous regions. Dynamic functional network connectivity (FNC) between all ICA time courses were computed using a tapered sliding window approach. We used a k-means algorithm to cluster the resulting dynamic FNC windows from each scan session into five dynamic states. We examined age and sex associations using linear mixed-effects models. First, independent from the dynamic states, we found a general increase in the temporal variability of the connections between intrinsic connectivity networks with increasing age. Second, when examining the clusters of dynamic FNC windows, we observed that the time spent in less modularized states, with low intra- and inter-network connectivity, decreased with age. Third, the number of transitions between states also decreased with age. Finally, compared to boys, girls showed a more mature pattern of dynamic brain connectivity, indicated by more time spent in a highly modularized state, less time spent in specific states that are frequently observed at a younger age, and a lower number of transitions between states. This longitudinal population-based study demonstrates age-related maturation in dynamic intrinsic neural activity from childhood into adolescence and offers a meaningful baseline for comparison with deviations from typical development. Given that several behavioral and cognitive processes also show marked changes through childhood and adolescence, dynamic functional connectivity should also be explored as a potential neurobiological determinant of such changes.

Pathogenesis of white matter changes in cerebral small vessel diseases: beyond vessel-intrinsic mechanisms

2017 ◽  
Vol 131 (8) ◽  
pp. 635-651 ◽  
Author(s):  
Anne Joutel ◽  
Hugues Chabriat
Keyword(s):  
White Matter ◽  
Current Knowledge ◽  
Large Population ◽  
Clinical Importance ◽  
Magnetic Resonance Images ◽  
Cerebrovascular Reactivity ◽  
Small Vessel ◽  
Oligodendrocyte Progenitor Cells ◽  
Perivascular Spaces ◽  
Cerebral Small Vessel Diseases

Cerebral small vessel diseases (SVDs) are a leading cause of age and hypertension-related stroke and dementia. The salient features of SVDs visible on conventional brain magnetic resonance images include white matter hyperintensities (WMHs) on T2-weighted images, small infarcts, macrohemorrhages, dilated perivascular spaces, microbleeds and brain atrophy. Among these, WMHs are the most common and often the earliest brain tissue changes. Moreover, over the past two decades, large population- and patient-based studies have established the clinical importance of WMHs, notably with respect to cognitive and motor disturbances. Here, we seek to provide a new and critical look at the pathogenesis of SVD-associated white matter (WM) changes. We first review our current knowledge of WM biology in the healthy brain, and then consider the main clinical and pathological features of WM changes in SVDs. The most widely held view is that SVD-associated WM lesions are caused by chronic hypoperfusion, impaired cerebrovascular reactivity (CVR) or blood–brain barrier (BBB) leakage. Here, we assess the arguments for and against each of these mechanisms based on population, patient and experimental model studies, and further discuss other potential mechanisms. Specifically, building on two recent seminal studies that have uncovered an anatomical and functional relationship between oligodendrocyte progenitor cells and blood vessels, we elaborate on how small vessel changes might compromise myelin remodelling and cause WM degeneration. Finally, we propose new directions for future studies on this hot research topic.

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