Genetic relatedness of axial and radial diffusivity indices of cerebral white matter microstructure in late middle age.
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ABSTRACT:
SUBMITTER: Hatton SN
PROVIDER: S-EPMC5895525 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is evidence that differences among individuals in white matter microstructure, as measured with diffusion tensor imaging (DTI), are under genetic control. However, little is known about the relative contribution of genetic and environmental effects on different diffusivity indices among late middle-aged adults. Here, we examined the magnitude of genetic influences for fractional anisotropy (FA), and mean (MD), axial (AD), and radial (RD) diffusivities in male twins aged 56-66 years old. Using an atlas-based registration approach to delineate individual white matter tracts, we investigated mean DTI-based indices within the corpus callosum, 12 bilateral tracts and all these regions of interest combined. All four diffusivity indices had high heritability at the global level (72%-80%). The magnitude of genetic effects in individual tracts varied from 0% to 82% for FA, 0% to 81% for MD, 8% to 77% for AD, and 0% to 80% for RD with most of the tracts showing significant heritability estimates. Despite the narrow age range of this community-based sample, age was correlated with all four diffusivity indices at the global level. In sum, all diffusion indices proved to have substantial heritability for most of the tracts and the heritability estimates were similar in magnitude for different diffusivity measures. Future studies could aim to discover the particular set of genes that underlie the significant heritability of white matter microstructure. Hum Brain Mapp 38:2026-2036, 2017. © 2017 Wiley Periodicals, Inc.
| S-EPMC5342936 | biostudies-literature
Project description:BackgroundDiffusion tensor imaging (DTI) magnetic resonance imaging (MRI) measuring fractional anisotropy (FA) and axial diffusivity (AD) may be a useful biomarker for monitoring changes in white matter after stroke, but its associations with upper-limb motor recovery have not been well studied. We aim to describe changes in the whole-brain FA and AD in five post-stroke patients in relation to kinematic measures of elbow flexion to better understand the relationship between FA and AD changes and clinico-kinematic measures of upper limb motor recovery.MethodsWe performed DTI MRI at two timepoints during the acute phase of stroke, measuring FA and AD across 48 different white matter tract regions in the brains of five hemiparetic patients with infarcts in the cortex, pons, basal ganglia, thalamus, and corona radiata. We tracked the progress of these patients using clinical Fugl-Meyer Assessments and kinematic measures of elbow flexion at the acute phase within 14 (mean: 9.4 ± 2.49) days of stroke symptom onset and at a follow-up appointment 2 weeks later (mean: 16 ± 1.54) days.ResultsChanges in FA and AD in 48 brain regions occurring during stroke rehabilitation are described in relation to motor recovery. In this case series, one patient with a hemipontine infarct showed an increase in FA of the ipsilateral and contralateral corticospinal tract, whereas other patients with lesions involving the corona radiata and middle cerebral artery showed widespread decreases in perilesional FA. On the whole, FA and AD seemed to behave inversely to each other.ConclusionsThis case series describes longitudinal changes in perilesional and remote FA and AD in relation to kinematic parameters of elbow flexion at the subacute post-stroke period. Although studies with larger sample sizes are needed, our findings indicate that longitudinally measured changes in DTI-based measurements of white matter microstructural integrity may aid in the prognostication of patients affected by motor stroke.
| S-EPMC6668170 | biostudies-literature
Project description:The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the "last-in-first-out") concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the p-values. Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.
| S-EPMC9201287 | biostudies-literature
Project description:BackgroundGulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction.MethodsGulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs.ResultsGulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis.ConclusionThe right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.
| S-EPMC3603990 | biostudies-literature
Project description:Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Because hypertension effects on the brain may vary with age, it is important to focus on middle age, when hypertension becomes more prevalent. We used linear mixed-effect models to examine differences in white matter diffusion metrics as a function of hypertension in a well-characterized cohort of middle-aged men (n=316; mean, 61.8 years; range, 56.7-65.6). Diffusion metrics were examined in 9 tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with long-standing hypertension (>5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than among noncarriers of the apolipoprotein E ?4 allele for 2 tracts connecting frontal regions with other brain areas. Significant differences were observed even after adjustment for potentially related lifestyle and cardiovascular risk factors. Shorter duration of hypertension or better blood pressure control among hypertensive individuals did not lessen the adverse effects. These findings suggest that microstructural white matter alterations appear early in the course of hypertension and may persist despite adequate treatment. Although longitudinal studies are needed to confirm these findings, the results suggest that prevention-rather than management-of hypertension may be vital to preserving brain health in aging.
| S-EPMC4499000 | biostudies-literature
Project description:Patterns of pubertal maturation have been linked to vulnerability for emotion dysregulation disorders in girls, as well as white matter (WM) development, suggestive of a potential mechanism between pubertal maturation and emotional health. Because pubertal processes begin at varying ages (i.e., status, timing) and proceed at varying rates (i.e., tempo), identifying individual differences in the pubertal course associated with subsequent WM microstructure development may reveal clues about neurobiological mechanisms of girls' emotional well-being. In a prospective cohort study of 107 girls, we examined associations between pubertal status at age 9, pubertal timing and tempo from ages 9-15, and WM microstructure at age 19. Tract-based spatial statistics revealed that girls with more advanced pubertal status at age 9, specific to gonadal-related physical changes, had higher fractional anisotropy, and lower mean diffusivity (MD) and radial diffusivity in tracts relevant to cognitive control and emotion regulation (e.g., the superior longitudinal fasciculus, external capsule, and uncinate fasciculus). Additionally, girls with earlier pubertal timing showed lower MD in the left anterior cingulum bundle. Tempo was unrelated to WM measures. These findings implicate specific aspects of pubertal maturation in subsequent neural signatures, suggesting possible neuroendocrine mechanisms relevant to emotional development. Future work incorporating longitudinal neuroimaging in parallel with pubertal measures may contribute to the understanding of individual variation in pubertal course and WM development.
| S-EPMC6296475 | biostudies-literature
Project description:ImportanceThere is a dearth of studies that examine the association between poorer hearing and change in cerebral white matter (WM) microstructure.ObjectiveTo examine the association of poorer hearing with baseline and change in WM microstructure among older adults.Design, setting, and participantsThis was a prospective cohort study that evaluated speech-in-noise, pure-tone audiometry, and WM microstructure, as measured by mean diffusivity (MD) and fractional anisotropy (FA), both of which were evaluated by diffusion tensor imaging (DTI) in 17 WM regions. Data were collected between October 2012 and December 2018 and analyzed between March 2019 and August 2019 with a mean follow-up time of 1.7 years. The study evaluated responses to the Baltimore Longitudinal Study of Aging among 356 cognitively normal adults who had at least 1 hearing assessment and DTI session. Excluded were those with baseline cognitive impairment, stroke, head injuries, Parkinson disease, and/or bipolar disorder.ExposuresPeripheral auditory function was measured by pure-tone average in the better-hearing ear. Central auditory function was measured by signal-to-noise ratio score from a speech-in-noise task and adjusted by pure-tone average.Main outcomes and measuresLinear mixed-effects models with random intercepts and slopes were used to examine the association of poorer peripheral and central auditory function with baseline and longitudinal DTI metrics in 17 WM regions, adjusting for baseline characteristics (age, sex, race, hypertension, elevated total cholesterol, and obesity).ResultsOf 356 cognitively normal adults included in the study, the mean (SD) age was 73.5 (8.8) years, and 204 (57.3%) were women. There were no baseline associations between hearing and DTI measures. Longitudinally, poorer peripheral hearing was associated with increases in MD in the inferior fronto-occipital fasciculus (β = 0.025; 95% CI, 0.008-0.042) and the body (β = 0.050; 95% CI, 0.015-0.085) of the corpus callosum, but there were no associations of peripheral hearing with FA changes in these tracts. Poorer central auditory function was associated with longitudinal MD increases (β = 0.031; 95% CI, 0.010-0.052) and FA declines (β = -1.624; 95% CI, -2.511 to -0.738) in the uncinate fasciculus.Conclusions and relevanceFindings of this cohort study suggest that poorer hearing is related to change in integrity of specific WM regions involved with auditory processing.
| S-EPMC7489397 | biostudies-literature
Project description:White matter microstructure is affected by immune system activity via the actions of circulating pro-inflammatory cytokines. Although white matter microstructure and inflammatory measures are significantly heritable, it is unclear if overlapping genetic factors influence these traits in humans. We conducted genetic correlation analyses of these traits using randomly ascertained extended pedigrees from the Genetics of Brain Structure and Function Study (N = 1862, 59% females, ages 18-97 years; 42 ± 15.7). White matter microstructure was assessed using fractional anisotropy (FA) calculated from diffusion tensor imaging (DTI). Circulating levels (pg/mL) of pro-inflammatory cytokines (IL-6, IL-8, and TNFα) phenotypically associated with white matter microstructure were quantified from blood serum. All traits were significantly heritable (h2 ranging from 0.41 to 0.66 for DTI measures and from 0.18 to 0.30 for inflammatory markers). Phenotypically, higher levels of circulating inflammatory markers were associated with lower FA values across the brain (r = -.03 to r = -.17). There were significant negative genetic correlations between most DTI measures and IL-8 and TNFα, although effects for TNFα were no longer significant when covarying for body mass index. Genetic correlations between DTI measures and IL-6 were not significant. Understanding the genetic correlation between specific inflammatory markers and DTI measures may help researchers focus questions related to inflammatory processes and brain structure.
| S-EPMC6707845 | biostudies-literature
Project description:ObjectiveDiffusion tensor imaging (DTI) quantifies Brownian motion of water within tissue. The goal of this study was to test whether, following a remote episode of optic neuritis (ON), breakdown of myelin and axons within the optic nerve could be detected by alterations in DTI parameters, and whether these alterations would correlate with visual loss.MethodsSeventy subjects with a history of ON > or =6 months prior underwent DTI of the optic nerves, assessment of visual acuities (VA) and contrast sensitivities (CS), and laboratory measures of visual evoked potentials (VEP) and optical coherence tomography (OCT).ResultsRadial diffusivity (RD) correlated with visual acuity (r = -0.61), Pelli-Robson CS (r = -0.60), 5%CS (r = 0.61), OCT (r = -0.78), VEP latency (r = 0.61), and VEP amplitude (r = -0.46). RD differentiated the unaffected fellow nerves from affected nerves in all visual outcome categories. RD also discriminated nerves with recovery to normal from mild visual impairment, and those with mild impairment from profound visual loss. RD differentiated healthy controls from both clinically affected nerves and unaffected fellow nerves after ON. RD differentiated all categories of 5%CS outcomes, and all categories of Pelli-Robson CS with the exception of normal recovery from mildly affected.ConclusionsIncreased optic nerve radial diffusivity (RD) detected by diffusion tensor imaging (DTI) was associated with a proportional decline in vision after optic neuritis. RD can differentiate healthy control nerves from both affected and unaffected fellow nerves. RD can discriminate among categories of visual recovery within affected eyes. Optic nerve injury as assessed by DTI was corroborated by both optical coherence tomography and visual evoked potentials.
| S-EPMC2882214 | biostudies-literature
Project description:Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model-diffusion tensor imaging (DTI)-and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
| S-EPMC9842921 | biostudies-literature