Increase In White Matter Volume Research Articles

White matter trajectories over the lifespan.

White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186 diffusion-weighted MRIs from participants between 2 weeks to 100 years of age. Age-related changes in gray matter and WM partial volumes and microstructural WM properties, both brain-wide and on 29 reconstructed tracts, were investigated as a function of biological sex and hemisphere, when appropriate. We investigated the curve fit that would best explain age-related differences by fitting linear, cubic, quadratic, and exponential models to macro and microstructural WM properties. Following the first steep increase in WM volume during infancy and childhood, the rate of development slows down in adulthood and decreases with aging. Similarly, microstructural properties of WM, particularly fractional anisotropy (FA) and mean diffusivity (MD), follow independent rates of change across the lifespan. The overall increase in FA and decrease in MD are modulated by demographic factors, such as the participant's age, and show different hemispheric asymmetries in some association tracts reconstructed via probabilistic tractography. All changes in WM macro and microstructure seem to follow nonlinear trajectories, which also differ based on the considered metric. Exponential changes occurred for the WM volume and FA and MD values in the first five years of life. Collectively, these results provide novel insight into how changes in different metrics of WM occur when a lifespan approach is considered.

Generative Sampling in Bundle Tractography using Autoencoders (GESTA).

Current tractography methods use the local orientation information to propagate streamlines from seed locations. Many such seeds provide streamlines that stop prematurely or fail to map the true white matter pathways because some bundles are "harder-to-track" than others. This results in tractography reconstructions with poor white and gray matter spatial coverage. In this work, we propose a generative, autoencoder-based method, named GESTA (Generative Sampling in Bundle Tractography using Autoencoders), that produces streamlines achieving better spatial coverage. Compared to other deep learning methods, our autoencoder-based framework uses a single model to generate streamlines in a bundle-wise fashion, and does not require to propagate local orientations. GESTA produces new and complete streamlines for any given white matter bundle, including hard-to-track bundles. Applied on top of a given tractogram, GESTA is shown to be effective in improving the white matter volume coverage in poorly populated bundles, both on synthetic and human brain in vivo data. Our streamline evaluation framework ensures that the streamlines produced by GESTA are anatomically plausible and fit well to the local diffusion signal. The streamline evaluation criteria assess anatomy (white matter coverage), local orientation alignment (direction), and geometry features of streamlines, and optionally, gray matter connectivity. The GESTA framework offers considerable gains in bundle overlap using a reduced set of seeding streamlines with a 1.5x improvement for the "Fiber Cup", and 6x for the ISMRM 2015 Tractography Challenge datasets. Similarly, it provides a 4x white matter volume increase on the BIL&GIN callosal homotopic dataset, and successfully populates bundles on the multi-subject, multi-site, whole-brain in vivo TractoInferno dataset. GESTA is thus a novel deep generative bundle tractography method that can be used to improve the tractography reconstruction of the white matter.

Learning-related contraction of gray matter in rodent sensorimotor cortex is associated with adaptive myelination.

From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural MRI, may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function, and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm in male mice to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole-brain VBM revealed nonlinear decreases in gray matter volume (GMV) juxtaposed to nonlinear increases in white matter volume (WMV) within GM that were best modeled by an asymptotic time course. Using an atlas-based cortical mask, we found nonlinear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. Further investigations using quantitative confocal microscopy confirmed these changes specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that nonlinear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex significantly correlated with myelin immunoreactivity. Together, these observations indicate a nonlinear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.

White matter alterations in familial cortical myoclonic tremor with epilepsy type 1.

Although previous imaging studies have reported cerebellar gray matter loss in patients with familial cortical myoclonic tremor with epilepsy (FCMTE), the corresponding white matter alterations remain unknown. We investigated white matter structural changes in FCMTE1 and compared them with clinical and electrophysiological features. We enrolled 36 patients carrying heterozygous pathogenic intronic pentanucleotide insertions in the SAMD12gene and 52 age- and sex-matched healthy controls. Diffusion tensor imaging-derived metrics, including fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated along with white matter voxel-based morphometry (VBM) analysis. We also examined correlations between magnetic resonance metrics and clinical and electrophysiological features. We detected widespread white matter reductions in MD, RD, and AD values in FCMTE1 patients, including in the commissural, projection, and association fibers. VBM analysis revealed that increases in white matter volume predominantly occurred in the right cerebellum and sagittal stratum. MD, RD, AD, and VBM analysis clearly indicated changes in the sagittal stratum. We found a positive correlation between VBM values in the right cerebellum and somatosensory-evoked potential P25-N33 amplitude. Decreased MD and AD values in the right sagittal stratum were detected in patients with versus without photophobia. FCMTE is a network disorder involving a wide range of cortical and subcortical structures, including the cerebellum, thalamus, thalamocortical connections, and corticocortical connections. The right sagittal stratum is closely related with visual symptoms, especially photophobia. Our findings indicate that cerebellum and cortical hyperexcitability are closely linked, and emphasize the important role of the cerebellum in the pathophysiological mechanisms of cortical tremor.

Alcohol use and brain morphology in adolescence: A longitudinal study in three different cohorts.

Alcohol consumption is commonly initiated during adolescence, but the effects on human brain development remain unknown. In this multisite study, we investigated the longitudinal associations of adolescent alcohol use and brain morphology. Three longitudinal cohorts in the Netherlands (BrainScale n = 200, BrainTime n = 239 and a subsample of the Generation R study n = 318) of typically developing participants aged between 8 and 29 years were included. Adolescent alcohol use was self‐reported. Longitudinal neuroimaging data were collected for at least two time points. Processing pipelines and statistical analyses were harmonized across cohorts. Main outcomes were global and regional brain volumes, which were a priori selected. Linear mixed effect models were used to test main effects of alcohol use and interaction effects of alcohol use with age in each cohort separately. Alcohol use was associated with adolescent's brain morphology showing accelerated decrease in grey matter volumes, in particular in the frontal and cingulate cortex volumes, and decelerated increase in white matter volumes. No dose–response association was observed. The findings were most prominent and consistent in the older cohorts (BrainScale and BrainTime). In summary, this longitudinal study demonstrated differences in neurodevelopmental trajectories of grey and white matter volume in adolescents who consume alcohol compared with non‐users. These findings highlight the importance to further understand underlying neurobiological mechanisms when adolescents initiate alcohol consumption. Therefore, further studies need to determine to what extent this reflects the causal nature of this association, as this longitudinal observational study does not allow for causal inference.

Inter-individual variability in structural brain development from late childhood to young adulthood

A fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined inter-individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0–26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable inter-individual variability in the magnitude of changes observed for all examined brain measures. The majority of individuals demonstrated decreases in total gray matter volume, cortex volume, mean cortical thickness, and white matter surface area in mid-adolescence, with more variability present during the transition into adolescence and the transition into early adulthood. While most individuals demonstrated increases in white matter volume in early adolescence, this shifted to a majority demonstrating stability starting in mid-to-late adolescence. We observed sex differences in these patterns, and also an association between the size of an individual's brain structure and the overall rate of change for the structure. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual- and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations.

Normative Analysis of Individual Brain Differences Based on a Population MRI-Based Atlas of Cynomolgus Macaques.

The developmental trajectory of the primate brain varies substantially with aging across subjects. However, this ubiquitous variability between individuals in brain structure is difficult to quantify and has thus essentially been ignored. Based on a large-scale structural magnetic resonance imaging dataset acquired from 162 cynomolgus macaques, we create a species-specific 3D template atlas of the macaque brain, and deploy normative modeling to characterize individual variations of cortical thickness (CT) and regional gray matter volume (GMV). We observed an overall decrease in total GMV and mean CT, and an increase in white matter volume from juvenile to early adult. Specifically, CT and regional GMV were greater in prefrontal and temporal cortices relative to early unimodal areas. Age-dependent trajectories of thickness and volume for each cortical region revealed an increase in the medial temporal lobe, and decreases in all other regions. A low percentage of highly individualized deviations of CT and GMV were identified (0.0021%, 0.0043%, respectively, P < 0.05, false discovery rate [FDR]-corrected). Our approach provides a natural framework to parse individual neuroanatomical differences for use as a reference standard in macaque brain research, potentially enabling inferences regarding the degree to which behavioral or symptomatic variables map onto brain structure in future disease studies.

Cognitive Improvement After Kidney Transplantation Is Associated With Structural and Functional Changes on MRI.

Several studies have reported improved cognitive outcomes after kidney transplantation, but most studies either did not include controls or lacked extensive neuroimaging. In addition, there is uncertainty whether kidney donation is a safe procedure in terms of cognitive outcomes. We prospectively studied neurocognitive function in kidney transplant recipients. The primary outcome was change in neurocognitive function after 1 year compared with baseline, which was evaluated using the Amsterdam Neuropsychological Task battery and verbal fluency tests. Secondary outcomes included changes in depression and anxiety (measured by the Hospital Anxiety and Depression scale) and changes in fatigue (measured by the Checklist for Individual Strength). We included kidney donors to control for learning effects, socioeconomic status, and surgery. In addition, kidney transplant recipients were evaluated with MRI scans at baseline and at year 1. The MRI protocol included conventional MRI, automated volumetric measurement, diffusion tensor imaging, magnetic resonance spectroscopy, arterial spin labeling, and a resting state functional MRI. Twenty-seven recipients and 24 donors were included. For both recipients and donors, neuropsychologic testing scores improved 1 year after transplantation (donation). Recipient improvement significantly exceeded donor improvement on tasks measuring attention and working memory. These improvements were associated with increases in white matter volume and N-acetylaspartate/creatine (a marker for neuronal integrity). Attention and working memory improve significantly 1 year after kidney transplantation. Learning effects do not account for these improvements because recipient improvement in these areas exceeds donor improvement and correlates with an improvement in white matter integrity after transplantation. Kidney donation appears to be a safe procedure in terms of cognitive outcomes.

Vasogenic Brain Edema During Maintenance Hemodialysis : Preliminary Results from Tract-based Spatial Statistics and Voxel-based Morphometry.

Hemodialysis (HD), especially when first initiated, can cause neurological deterioration. Presumably this is due to transient cerebral edema, which has been observed using diffusion weighted magnetic resonance imaging (MRI) in experimental and human studies; however, this has not been investigated under maintenance hemodialysis (mHD). Moreover, there are no studies to date investigating regional effects of mHD on grey and white matter volumes. In this study eight patients with end stage renal disease (ESRD) were examined immediately before and after mHD sessions with multimodal MRI, including diffusion tensor imaging (DTI) and high-resolution structural imaging. Additionally, eight healthy, age-matched and sex-matched controls were examined for comparison. Data were analyzed using tract-based spatial statistics and voxel-based morphometry. At baseline, ESRD patients had significantly reduced values of fractional anisotropy (FA) and axial diffusivity as well as bilaterally reduced grey matter volume in the insula, compared with controls. After the mHD session, FA further decreased while axial, radial, and mean diffusivity significantly increased ubiquitously throughout the white matter. Voxel-based morphometry revealed acorresponding significant increase in white matter volume in the central right hemisphere and splenium, as well as in cortical grey matter in the anterior medial frontal and cingulate cortex. None of the patients showed neurological deterioration. In this study ESRD patients showed white matter changes indicative of chronic microstructural damage when compared with healthy controls, as previously reported. In addition, patients showed signs of atransient extracellular cerebral edema, which has not yet been observed in the absence of neurological symptoms.

S182. CHANGE IN CORTICAL MORPHOMETRY IN INDIVIDUALS WITH PERSISTING PSYCHOTIC EXPERIENCES: A LONGITUDINAL PILOT STUDY

BackgroundThere is an increasing interest in the presence of psychotic symptoms in the general population that do not meet the threshold for psychotic disorder. Such psychotic experiences (PEs) are more prevalent than conditions such as schizophrenia and often manifest during childhood and adolescence. PEs are a risk factor for psychotic disorders and a range of adverse psychosocial outcomes. PEs can become abnormally persistent with a corresponding increase in psychiatric morbidity. Previous research has highlighted subtle deviations in brain structure associated with the presence and persistence of PEs, but longitudinal assessments are needed to gauge if these deviations continue, perhaps as part of an atypical neurodevelopmental trajectory.MethodsLongitudinal imaging data, taken at ages 20 and 25, were available for 25 young adults who were part an MRI nested case control study within the Avon Longitudinal Study of Parents and Children. They were selected originally on the basis of presence or absence of PEs. Cortical surface data were analysed using Freesurfer. Presence of PEs was assessed at ages 18, 20, and 25 and we defined persistence as endorsing PEs at multiple time-points. Average cortical volume and thickness were extracted from each brain parcellation. We additionally calculated fractal dimensionality (FD) of each parcellation using a box-count algorithm to capture shape complexity. We compared the rate of change between healthy controls (HC) and those with persistent PEs in each parcellation and used permutation testing to control for multiple comparisons.ResultsBoth HC and PEs showed the expected age-related net loss in brain volume; an increase in white matter volume offset by a greater reduction in grey matter. We identified greater volume loss in PEs in the left parietal lobe and further examination of local volume highlighted additional changes. PEs were associated with a greater rate of volume loss in the anterior cingulate, postcentral, and lingual gyrus in the left hemisphere and in the right inferior parietal lobule and pars orbitalis. Thinning of the left inferior parietal lobule was greater in those with PEs. There was further converging evidence of focal abnormalities in the left postcentral gyrus in terms of reductions in cortical thickness and FD in PEs. Similarly, we found reduced FD relative to HC in the left rostral anterior cingulate. There was additional evidence for reductions in FD in the left hemisphere in the cuneus, isthmus cingulate, and middle frontal gyrus.DiscussionOur findings highlight a deviation from typical age-related changes in brain volume in individuals with persisting manifestations of PEs. Though these changes could reflect an acceleration of the typical volume loss that is seen with aging, there are several points of evidence against this. We found no differences in global volume changes and only the left parietal lobule was found to show a greater volume loss in PEs. On a local scale, findings seemed to mostly converge on parietal and cingulate regions in the left hemisphere with some evidence of aberrations in frontal regions. These pilot data are, uniquely, unconfounded by illness and treatment related factors and highlight the continued need for longitudinal assessments of brain structure in relation to PEs; there is an increasing risk of transitioning to a psychotic disorder with persistence of PEs and our findings may reflect the neuroanatomical basis for an anomalous developmental trajectory related to psychotic disorders.

Initial body fat gain is related to brain volume changes in adolescents: A repeated-measures voxel-based morphometry study.

Individuals with obesity versus those within a healthy weight range show brain volume differences, but it is unclear whether these differences reflect initial vulnerability factors or are secondary to weight gain. One hundred sixty-two adolescents (M age = 15.3 ± 1.1; 81 females) with healthy weight were scanned at baseline. Sixty subjects (M baseline age: 15.2 ± 1.1; M follow-up age: 17.7 ± 1.2; 34 females) completed a second scan at 2- or 3-year follow-up. Voxel-based morphometry assessed global and regional gray matter (GM) and white matter (WM) volumes. Body fat percentage was assessed yearly over follow-up. Baseline global/regional GM/WM volume did not predict body fat gain over follow-up. Adolescents who gained body fat showed greater decreases in GM volume in the putamen compared with those who showed loss of body fat. Adolescents who gained body fat showed greater increases in WM volume in the anterior cingulate cortex compared with those who showed stability of or loss of body fat. Body fat gain versus stability and loss produce GM and WM volume changes, rather than baseline volumetric differences predicting body fat gain.

Multiparametric Magnetic Resonance Investigation of Brain Adaptations to 6 Days at 4350 m.

Objective: Hypoxic exposure in healthy subjects can induce acute mountain sickness including headache, lethargy, cerebral dysfunction, and substantial cerebral structural alterations which, in worst case, can lead to potentially fatal high altitude cerebral edema. Within this context, the relationships between high altitude-induced cerebral edema, changes in cerebral perfusion, increased brain parenchyma volume, increased intracranial pressure, and symptoms remain unclear.Methods: In 11 subjects before and after 6 days at 4350 m, we performed multiparametric magnetic resonance investigations including anatomical, apparent diffusion coefficient and arterial spin labeling sequences.Results: After the altitude stay, while subjects were asymptomatic, white matter volume (+0.7 ± 0.4%, p = 0.005), diffusion (+1.7 ± 1.4%, p = 0.002), and cerebral blood flow (+28 ± 38%; p = 0.036) were significantly increased while cerebrospinal fluid volume was reduced (−1.4 ± 1.1%, p = 0.009). Optic nerve sheath diameter (used as an index of increased intracranial pressure) was unchanged from before (5.84 ± 0.53 mm) to after (5.92 ± 0.60 mm, p = 0.390) altitude exposure. Correlations were observed between increases in white matter volume and diffusion (rho = 0.81, p = 0.016) and between changes in CSF volume and changes in ONSD s (rho = −0.92, p = 0.006) and symptoms during the altitude stay (rho = −0.67, p = 0.031).Conclusions: These data demonstrate white matter alterations after several days at high altitude when subjects are asymptomatic that may represent the normal brain response to prolonged high altitude exposure.

Urban air pollution affects structural and functional processes of brain maturation in children

Introduction From conception to young adulthood, the human brain undergoes dynamic changes in both its structural and functional organization. This period of life is particularly vulnerable to environmental insults that may interfere with the cascade of neurodevelopmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution exposure during the prenatal period and the childhood. Methods A group of 263 children, aged 8 to 12 years, underwent magnetic resonance imaging to quantify regional brain volumes and functional connectivity in major neural networks and activation / deactivation dynamics during a sensory task. Prenatal NO2 exposure was estimated using both the mothers address during pregnancy and the data from an urban background monitoring station. A combined measurement of elemental carbon and NO2 in the school environment was used to assess urban air pollution exposure during the childhood period. Results While the children exposed to low prenatal NO2 levels showed an increase in white matter volume (WMV) with advancing age, no WMV progression was observed in the children exposed to higher prenatal levels. Similarly, in the opposite effect to that of age, a higher content of pollutants in the school environment was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Conclusion Both prenatal and postnatal air pollution exposure appear to adversely affect the structural and functional brain maturation. Further research is needed to determine to what extent these disruptions in the brain maturation process are involved in the poor cognitive performance previously observed in children exposed to air pollution.

Alcohol and Drug Use and the Developing Brain.

Adolescence is an important neurodevelopmental period marked by rapidly escalating rates of alcohol and drug use. Over the past decade, research has attempted to disentangle pre- and post-substance use effects on brain development by using sophisticated longitudinal designs. This review focuses on recent, prospective studies and addresses the following important questions: (1) what neuropsychological and neural features predate adolescent substance use, making youth more vulnerable to engage in heavy alcohol or drug use, and (2) how does heavy alcohol and drug use affect normal neural development and cognitive functioning? Findings suggest that pre-existing neural features that relate to increased substance use during adolescence include poorer neuropsychological functioning on tests of inhibition and working memory, smaller gray and white matter volume, changes in white matter integrity, and altered brain activation during inhibition, working memory, reward, and resting state. After substance use is initiated, alcohol and marijuana use are associated with poorer cognitive functioning on tests of verbal memory, visuospatial functioning, psychomotor speed, working memory, attention, cognitive control, and overall IQ. Heavy alcohol use during adolescence is related to accelerated decreases in gray matter and attenuated increases in white matter volume, as well as increased brain activation during tasks of inhibition and working memory, relative to controls. Larger longitudinal studies with more diverse samples are needed to better understand the interactive effects of alcohol, marijuana, and other substances, as well as the role of sex, co-occurring psychopathology, genetics, sleep, and age of initiation on substance use.

The Puzzle of Structural Brain Connectivity Following Traumatic Incidents

The Puzzle of Structural Brain Connectivity Following Traumatic Incidents

Synergistic Effects of Age on Patterns of White and Gray Matter Volume across Childhood and Adolescence

The human brain develops with a nonlinear contraction of gray matter across late childhood and adolescence with a concomitant increase in white matter volume. Across the adult population, properties of cortical gray matter covary within networks that may represent organizational units for development and degeneration. Although gray matter covariance may be strongest within structurally connected networks, the relationship to volume changes in white matter remains poorly characterized. In the present study we examined age-related trends in white and gray matter volume using T1-weighted MR images from 360 human participants from the NIH MRI study of Normal Brain Development. Images were processed through a voxel-based morphometry pipeline. Linear effects of age on white and gray matter volume were modeled within four age bins, spanning 4-18 years, each including 90 participants (45 male). White and gray matter age-slope maps were separately entered into k-means clustering to identify regions with similar age-related variability across the four age bins. Four white matter clusters were identified, each with a dominant direction of underlying fibers: anterior–posterior, left–right, and two clusters with superior–inferior directions. Corresponding, spatially proximal, gray matter clusters encompassed largely cerebellar, fronto-insular, posterior, and sensorimotor regions, respectively. Pairs of gray and white matter clusters followed parallel slope trajectories, with white matter changes generally positive from 8 years onward (indicating volume increases) and gray matter negative (decreases). As developmental disorders likely target networks rather than individual regions, characterizing typical coordination of white and gray matter development can provide a normative benchmark for understanding atypical development.

PO-0470 Stereologic Quantification Of Brain Volume Development In Preterm Pigs In The Perinatal Period

Background and aims Preterm birth is associated with an increased risk of brain injury, smaller brain volume and cognitive deficits. To gain insight into how premature birth affects brain development in a pig model of preterm birth, we evaluated the growth of the neocortex and cerebellum using designed based stereology. Methods Piglets born preterm or at term (postconceptional age (PA) 106 and 118, respectively) were euthanized on postnatal day 0, 5 or 26 (n = 1–22). The left cerebral and cerebellar hemipheres were fixed in formalin, embedded in agar, and sectioned coronally. The grey and white matter volumes were estimated using the Cavalieri method. Data were analysed by ANCOVA including PA, postnatal age, weight, litter, and gender as covariates. Results Cerebral and cerebellar grey and white matter volumes increased significantly with PA and postnanal age (p Conclusions The large increase in white matter volume during the last 12 days of fetal life suggests that this is a very sensitive period for brain growth in the piglet. These data are in agreement with human studies and thus supports the use of the preterm pig as a model for brain development in premature human infants.

Cerebral volumetric changes induced by prolonged hypoxic exposure and whole-body exercise.

The present study assessed the isolated and synergetic effects of hypoxic exposure and prolonged exercise on cerebral volume and subedema and symptoms of acute mountain sickness (AMS). Twelve healthy males performed three semirandomized blinded 11-hour sessions with (1) an inspiratory oxygen fraction (FiO2) of 12% and 4-hour cycling, (2) FiO2=21% and 4-hour cycling, and (3) FiO2=8.5% to 12% at rest (matching arterial oxygen saturation measured during the first hypoxic session). Volumetric, apparent diffusion coefficient (ADC), and arterial spin labelling 3T magnetic resonance imaging sequences were performed after 30 minutes and 10 hours in each session. Thirty minutes of hypoxia at rest induced a significant increase in white-matter volume (+0.8±1.0% compared with normoxia) that was exacerbated after 10 hours of hypoxia at rest (+1.5±1.1%) or with cycling (+1.6±1.1%). Total brain parenchyma volume increased significantly after 10 hours of hypoxia with cycling only (+1.3±1.1%). Apparent diffusion coefficient was significantly reduced after 10 hours of hypoxia at rest or with cycling. No significant change in cerebral blood flow was observed. These results demonstrate changes in white-matter volume as early as after 30 minutes of hypoxia that worsen after 10 hours, probably due to cytotoxic edema. Exercise accentuates the effect of hypoxia by increasing total brain volume. These changes do not however correlate with AMS symptoms.

White matter integrity in older females is altered by increased body fat.

ObjectiveTo assess whether the pattern of diffusion changes among a cohort of individuals showing BMI-related increases in white matter volume reflects healthy expansion of myelin or damaged white matter.Design and MethodsDiffusion MRI measures (axial, radial, and fractional anisotropy) were obtained from 94 females, ages 52–92. Relationships between BMI and diffusion measures were assessed controlling for age, hypertension, and diabetes status using general linear modelling. Associations between diffusion measures and cognitive status (memory, executive functions, and visuomotor speed) were assessed using multiple regressions, controlling for age, education, hypertension, and diabetes status.ResultsHigher levels of BMI were associated with lower axial diffusion in frontal, temporal, parietal, internal capsule, and cerebellar white matter. Lower fractional anisotropy was observed in bilateral temporal white matter and the right corticospinal tract, with high radial diffusion in temporal and temporoparietal white matter. Importantly, diffusion measures predicted reductions in executive functioning, memory, and visuomotor speed.ConclusionsThe pattern of diffusion changes in regions of white matter showing BMI-related volume increases are not due to expansion of normal myelin, but instead suggest damage to white matter that has important consequences for cognitive functioning.

Effects of prenatal alcohol exposure on the development of white matter volume and change in executive function.

Prenatal alcohol exposure can cause a wide range of deficits in executive function that persist throughout life, but little is known about how changes in brain structure relate to cognition in affected individuals. In the current study, we predicted that the rate of white matter volumetric development would be atypical in children with fetal alcohol spectrum disorders (FASD) when compared to typically developing children, and that the rate of change in cognitive function would relate to differential white matter development between groups. Data were available for 103 subjects [49 with FASD, 54 controls, age range 6–17, mean age = 11.83] with 153 total observations. Groups were age-matched. Participants underwent structural magnetic resonance imaging (MRI) and an executive function (EF) battery. Using white matter volumes measured bilaterally for frontal and parietal regions and the corpus callosum, change was predicted by modeling the effects of age, intracranial volume, sex, and interactions with exposure status and EF measures. While both groups showed regional increases in white matter volumes and improvement in cognitive performance over time, there were significant effects of exposure status on age-related relationships between white matter increases and EF measures. Specifically, individuals with FASD consistently showed a positive relationship between improved cognitive function and increased white matter volume over time, while no such relationships were seen in controls. These novel results relating improved cognitive function with increased white matter volume in FASD suggest that better cognitive outcomes could be possible for FASD subjects through interventions that enhance white matter plasticity.