Biology subjects

Hoagey, D. A.

Publications and source records attributed to Hoagey, D. A..

7 recordsLinked to original sources

bioRxiv2025

Age-related cerebello-thalamo-cortical white matter degradation and executive function performance across the lifespan

The cerebellum supports higher-order cognition, such as working memory and executive function (EF) both directly and through connection with prefrontal areas via cortical loops. Thus, age-related degradation to white matter connectivity comprising cerebello-thalamo-cortical (CTC) loops may underlie age-related differences in EF. In 190 healthy adults (aged 20-94 years) we collected diffusion tensor imaging scans and multiple tests of working memory and EF. Deterministic tractography was used to generate CTC tracts from which white matter metrics (mean, radial, axial diffusivities) were extracted. General linear model results indicated that reduced white matter integrity (i.e., higher diffusivity) was associated with significantly poorer EF performance in an age-dependent fashion. Higher mean, radial, and axial diffusivities in fronto-cerebellar white matter was associated with lower EF scores in older, but not younger, adults. These findings suggest CTC white matter connectivity is important for executive function performance and lend mechanistic evidence to the role of the cerebellum in age-related differences in higher-order cognitive operations.

neuroscience↗

bioRxiv2024

Coupled aging of cyto- and myeloarchitectonic atlas-informed gray and white matter structural properties

A key aspect of brain aging that remains poorly understood is its high regional heterogeneity and heterochronicity. A better understanding of how the structural organization of the brain shapes aging trajectories is needed. Neuroimaging tissue "types" are often collected and analyzed as separate acquisitions, an approach that cannot provide a holistic view of age-related change of the related portions of the neurons (cell bodies and axons). Because neuroimaging can only assess indirect features at the gross macrostructural level, incorporating post-mortem histological information may aid in better understanding of structural aging gradients. Longitudinal design, coupling of gray and white matter (GM, WM) properties, and a biologically informed approach to organizing neural properties are needed. Thus, we tested aging of the regional coupling between GM (cortical thickness, surface area, volume) and WM (fractional anisotropy, mean, axial, and radial diffusivities) structural metrics using linear mixed effects modeling in 102 healthy adults aged 20-94 years old, scanned on two occasions over a four-year period. The association between age-related within-person change in GM morphometry and the diffusion properties of the directly neighboring portion of white matter were assessed, capturing both aspects of neuronal health in one model. Additionally, we parcellated the brain utilizing the histological-staining informed von Economo-Koskinas atlas to consider regional cyto- and myelo-architecture. Results demonstrate several gradients of coupled association in the age-related decline of neighboring white and gray matter. Most notably, gradients of coupling along the heteromodal association to sensory axis were found for several areas (e.g., anterior frontal and lateral temporal cortices, vs pre- and post-central gyrus, occipital, and limbic areas), in line with heterochronicity and retrogenesis theories of aging. Further effort to bridge across data and measurement scales will enhance understanding of the mechanisms of the aging brain.

neuroscience↗

bioRxiv2023

Differential effects of aging on regional corpus callosum microstructure and the modifying influence of pulse pressure

The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by vascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anterior-to-posterior gradient of vulnerability to aging that may be altered by effects of vascular health. In 174 healthy adults across the adult lifespan (mean age=53.56 {+/-} 18.90, range=20-94 years old, 58.62% women), measures of pulse pressure and diffusion-weighted imaging were conducted. A deterministic tractography approach was utilized to extract fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested effects of age, hypertension, and pulse pressure on these metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age x pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed non-linear components and occurred along an anterior-posterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable, and that pulse pressure, a proxy of arterial stiffness, alters this aging pattern. Significance StatementAging is associated with microstructural changes in the corpus callosum, the largest white matter tract in the brain. Additionally, vascular factors, such as hypertension and pulse pressure, affect corpus callosum microstructure. However, it is unclear whether these factors uniformly impact the corpus callosum throughout aging. The current study aimed to characterize patterns of aging and assess the role of hypertension and pulse pressure across different subregions of the corpus callosum. We found an age-related gradient on corpus callosum microstructure, with the most pronounced impact on anterior regions. However, this gradient was not found when pulse pressure was considered. These findings suggest that subregions are differentially sensitive to age-related decline, and pulse pressure modifies and exacerbates these declines.

neuroscience↗

bioRxiv2020

Age-related degradation of optic radiation white matter connectivity differentially predicts visual and non-visual executive functions

Healthy aging is accompanied by degraded white matter connectivity, which has been suggested to contribute to cognitive dysfunction observed in aging, especially in relation to fluid measures of cognition. Prior research linking white matter microstructure and cognition, however, has largely been limited to major association and heteromodal white matter tracts. The optic radiations (OR), which transfer visual sensory-perceptual information from thalamic lateral geniculate nucleus to primary visual cortex, are generally considered lower-level input-relay white matter tracts. However, the role of this prominent white-matter visual relay system in supporting higher-order cognition is understudied, especially in regard to healthy aging. The present study used deterministic tractography to isolate OR fractional anisotropy (FA) in 130 participants aged 20-94 to assess age effects on OR tract white matter. We also examined associations between age-related differences in the OR and cognitive domains involving visual processing speed, and visual- and non-visual executive function (EF). OR microstructure, as indexed by FA, exhibited a significant linear decrease across age. A significant interaction between age, FA, and cognitive domain on cognitive task performance indicated that in older age, more degraded OR white matter was associated with poorer visual EF, but no age-related association between FA in the OR and visual processing speed or verbal EF was observed. These findings suggest the optic radiations are not merely sensory-perceptual relays, but also influence higher-order visual cognition differentially with age.

neuroscience↗

bioRxiv2020

The effect of vascular health factors on white matter microstructure mediates age-related differences in executive function performance

Even within healthy aging, vascular risk factors can detrimentally influence cognition, with executive functions (EF) particularly vulnerable. Fronto-parietal white matter (WM) connectivity in part, supports EF and may be particularly sensitive to vascular risk. Here, we utilized structural equation modeling in 184 healthy adults (aged 20-94 years of age) to test the hypotheses that: 1) fronto-parietal WM microstructure mediates age effects on EF; 2) higher blood pressure (BP) and white matter hyperintensity (WMH) burden influences this association. All participants underwent comprehensive cognitive and neuropsychological testing including tests of processing speed, executive function (with a focus on tasks that require switching and inhibition) and completed an MRI scanning session that included FLAIR imaging for semi-automated quantification of white matter hyperintensity burden and diffusion-weighted imaging for tractography. Structural equation models were specified with age (as a continuous variable) and blood pressure predicting within-tract WMH burden and fractional anisotropy predicting executive function and processing speed. Results indicated that fronto-parietal white matter of the genu of the corpus collosum, superior longitudinal fasciculus, and the inferior frontal occipital fasciculus (but not cortico-spinal tract) mediated the association between age and EF. Additionally, increased systolic blood pressure and white matter hyperintensity burden within these white matter tracts contribute to worsening white matter health and are important factors underlying age-brain-behavior associations. These findings suggest that aging brings about increases in both BP and WMH burden, which may be involved in the degradation of white matter connectivity and in turn, negatively impact executive functions as we age.

neuroscience↗

bioRxiv2019

Joint contributions of cortical morphometry and white matter microstructure in healthy brain aging: A partial least squares correlation analysis

Cortical atrophy and degraded axonal health have been shown to coincide during normal aging; however, few studies have examined these measures together. To lend insight into both the regional specificity and the relative timecourse of structural degradation of these tissue compartments across the lifespan, we analyzed grey matter (GM) morphometry (cortical thickness, surface area, volume) and estimates of white matter (WM) microstructure (fractional anisotropy, mean diffusivity) using traditional univariate and more robust multivariate techniques to examine age associations in 186 healthy adults aged 20-94 years old. Univariate analysis of each tissue type revealed that negative age associations were largest in frontal grey and white matter tissue and weaker in temporal, cingulate, and occipital regions, representative of not only an anterior-to-posterior gradient, but also a medial-to-lateral gradient. Multivariate partial least squares correlation (PLSC) found the greatest covariance between GM and WM was driven by the relationship between WM metrics in the anterior corpus callosum and projections of the genu, anterior cingulum, and fornix; and with GM thickness in parietal and frontal regions. Surface area was far less susceptible to age effects and displayed less covariance with WM metrics, while regional volume covariance patterns largely mirrored those of cortical thickness. Results support a retrogenesis-like model of aging, revealing a coupled relationship between frontal and parietal GM and the underlying WM, which evidence the most protracted development and the most vulnerability during healthy aging.

neuroscience↗

bioRxiv2019

Contributions of white matter connectivity and BOLD modulation to cognitive aging: A lifespan structure-function association study

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent MRI scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered BOLD modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.

neuroscience↗