Heterogeneity in longitudinal deterioration of white matter microstructural integrity in the population and its implications for cognitive aging

BackgroundThe relationship between white-matter tracts and executive functions (EF) in attention deficit hyperactivity disorder (ADHD) has not been well studied and previous studies mainly focused on frontostriatal (FS) tracts. The authors explored the microstructural property of several fibre tracts hypothesized to be involved in EF, to correlate their microstructural property with EF, and to explore whether such associations differ between ADHD and typically developing (TD) youths.MethodWe assessed 45 youths with ADHD and 45 individually matched TD youths with a computerized test battery for multiple dimensions of EF. From magnetic resonance imaging, FS tract, superior longitudinal fasciculus (SLF), arcuate fasciculus (AF) and cingulum bundle (CB) were reconstructed by diffusion spectrum imaging tractography. The generalized fractional anisotropy (GFA) values of white-matter tracts were computed to present microstructural property of each tract.ResultsWe found lower GFA in the left FS tract, left SLF, left AF and right CB, and poorer performance in set-shifting, sustained attention, cognitive inhibition and visuospatial planning in ADHD than TD. The ADHD and TD groups demonstrated different association patterns between EF and fibre tract microstructural property. Most of the EF were associated with microstructural integrity of the FS tract and CB in TD youths, while with that of the FS tract, SLF and AF in youths with ADHD.ConclusionsOur findings support that the SLF, AF and CB also involve in a wide range of EF and that the main fibre tracts involved in EF are different in youths with ADHD.

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Microstructural degeneration underlies executive dysfunction after stroke

10.1101/2020.02.03.20020131 ◽

2020 ◽

Author(s):

Michele Veldsman ◽

Emilio Werden ◽

Natalia Egorova ◽

Mohamed Salah Khlif ◽

Amy Brodtmann

Keyword(s):

Executive Function ◽

White Matter ◽

Structural Equation ◽

Executive Dysfunction ◽

White Matter Integrity ◽

Stroke Severity ◽

Lesion Volume ◽

Stroke Patients ◽

Cerebrovascular Risk ◽

Microstructural Integrity

ABSTRACTObjectiveExecutive dysfunction affects 40% of stroke patients and is associated with poor quality of life. Stroke severity and lesion volume rarely predict whether a patient will have executive dysfunction. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We investigated whether measures of white matter microstructural integrity and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity.MethodsWe used structural equation modelling to examine multivariate relationships between cerebrovascular risk, white matter microstructural integrity (fractional anisotropy and mean diffusivity), stroke characteristics and executive dysfunction in 126 stroke patients (mean age 68.4 years), three months post-stroke, and compared to 40 age- and sex-matched control participants. Executive function was measured using the Trail Making Tests, Clock Drawing task and Rey Complex Figure copy task. Microstructural integrity was estimated using a standard pipeline to process diffusion weighted images.ResultsExecutive function was below what would be expected for age and education level in stroke patients (t-test compared to controls t(79)=5.75, p<0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk. Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity, than executive dysfunction and stroke severity. Mediation analysis showed the relationship between executive function and white matter integrity is mediated by cerebrovascular burden.InterpretationWhite matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity.

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Microstructural Integrity of White Matter Moderates an Association Between Childhood Adversity and Adult Trait Anger

10.1101/307637 ◽

2018 ◽

Cited By ~ 1

Author(s):

M. Justin Kim ◽

Maxwell L. Elliott ◽

Tracy C. d’Arbeloff ◽

Annchen R. Knodt ◽

Spenser R. Radtke ◽

...

Keyword(s):

Prefrontal Cortex ◽

Individual Differences ◽

White Matter ◽

Negative Emotion ◽

Childhood Adversity ◽

Trait Anger ◽

Uncinate Fasciculus ◽

Imaging Data ◽

Wide Range ◽

Microstructural Integrity

AbstractAmongst a number of negative life sequelae associated with childhood adversity is the later expression of a higher dispositional tendency to experience anger and frustration to a wide range of situations (i.e., trait anger). We recently reported that an association between childhood adversity and trait anger is moderated by individual differences in both threat-related amygdala activity and executive control-related dorsolateral prefrontal cortex (dlPFC) activity, wherein individuals with relatively low amygdala and high dlPFC activity do not express higher trait anger even when having experienced childhood adversity. Here, we examine possible structural correlates of this functional dynamic using diffusion magnetic resonance imaging data from 647 young adult men and women volunteers. Specifically, we tested whether the degree of white matter microstructural integrity as indexed by fractional anisotropy modulated the association between childhood adversity and trait anger. Our analyses revealed that higher microstructural integrity of multiple pathways was associated with an attenuated link between childhood adversity and adult trait anger. Amongst these pathways was the uncinate fasciculus, which not only provides a major anatomical link between the amygdala and prefrontal cortex but also is associated with individual differences in regulating negative emotion through top-down cognitive reappraisal. These findings suggest that higher microstructural integrity of distributed white matter pathways including but not limited to the uncinate fasciculus may represent an anatomical foundation serving to buffer against the expression of childhood adversity as later trait anger, which is itself associated with multiple negative health outcomes.

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Loss of White Matter Microstructural Integrity Is Associated with Adverse Neurological Outcome in Tuberous Sclerosis Complex

Academic Radiology ◽

10.1016/j.acra.2011.08.016 ◽

2012 ◽

Vol 19 (1) ◽

pp. 17-25 ◽

Cited By ~ 81

Author(s):

Jurriaan M. Peters ◽

Mustafa Sahin ◽

Vanessa K. Vogel-Farley ◽

Shafali S. Jeste ◽

Charles A. Nelson ◽

...

Keyword(s):

White Matter ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Neurological Outcome ◽

Microstructural Integrity

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Abstract TP75: Normal Appearing White Matter Integrity and Motor Impairment Severity in Acute Ischemic Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp75 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Carson Ingo ◽

Chen Lin ◽

James Higgins ◽

Yurany Arevalo ◽

Shyam Prabhakaran

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Motor Function ◽

Motor Impairment ◽

Internal Capsule ◽

Posterior Limb ◽

Normal Appearing White Matter ◽

Stroke Group ◽

Microstructural Integrity

Introduction: The effect of white matter hyperintensities (WMH) as measured by fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging on functional impairment and recovery after ischemic stroke has been investigated thoroughly. However, there has been growing interest to investigate normal-appearing white matter (NAWM) microstructural integrity following ischemic stroke onset with techniques such as diffusion tensor imaging (DTI). Methods: 52 patients with acute ischemic stroke and 36 without stroke were evaluated with a DTI and FLAIR imaging protocol and clinically assessed for severity of motor impairment using the Motricity Index within 72 hours of suspected symptom onset. Results: There were widespread decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) and radial diffusivity (RD) for the acute stroke group compared to the non-stroke group. As shown in the abstract figure with the blue voxels, there was a significant positive association between FA and motor function and a significant negative association between MD/RD and motor function. The NAWM regions of interest that were most sensitive to the Motricity Index were the anterior/posterior limb of the internal capsule in the infarcted hemisphere and the splenium of the corpus callosum, external capsule, posterior limb/retrolenticular part of the internal capsule, superior longitudinal fasciculus, and cingulum (hippocampus) of the intra-/contralateral hemisphere. Conclusion: The microstructural integrity of NAWM is a significant parameter to identify neural differences not only between those individuals with and without acute ischemic stroke, but also correlated with severity of acute motor impairment.

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Abstract P366: High Burden of Tract-Specific White Matter Hyperintensities Relates to Impaired Microstructural Integrity of Distal White Matter Tracts in Community-Dwelling Elders

Stroke ◽

10.1161/str.52.suppl_1.p366 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

YANPENG LIU ◽

YIWEI XIA ◽

XIAOXIAO WANG ◽

YI WANG ◽

LUMENG YANG ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Dysfunction ◽

White Matter Hyperintensities ◽

Brain Mri ◽

Mean Diffusivity ◽

Community Dwelling ◽

Superior Longitudinal Fasciculus ◽

High Burden ◽

Microstructural Integrity

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.

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White Matter Microstructural Differences in Youth with Classical Congenital Adrenal Hyperplasia

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab520 ◽

2021 ◽

Author(s):

Devyn L Cotter ◽

Anisa Azad ◽

Ryan P Cabeen ◽

Mimi S Kim ◽

Mitchell E Geffner ◽

...

Keyword(s):

White Matter ◽

Congenital Adrenal Hyperplasia ◽

Stria Terminalis ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Brain White Matter ◽

White Matter Microstructure ◽

Subcortical Regions ◽

21 Hydroxylase Deficiency ◽

Microstructural Integrity

Abstract Context Gray matter morphology in the prefrontal cortex and subcortical regions, including the hippocampus and amygdala, are affected in youth with classical congenital adrenal hyperplasia (CAH). It remains unclear if white matter connecting these aforementioned brain regions is compromised in youth with CAH. Objective To examine brain white matter microstructure in youth with CAH compared to controls. Design A cross-sectional sample of 23 youths with CAH due to 21-hydroxylase deficiency (12.9±3.5 year; 61% female) and 33 healthy controls (13.1±2.8 year; 61% female) with 3T multi-shell diffusion-weighted magnetic resonance brain scans. Main Outcome Measures Complementary modeling approaches, including diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI), to examine in vivo white matter microstructure in six white matter tracts that innervate the prefrontal and subcortical regions. Results DTI showed CAH youth had lower fractional anisotropy in both the fornix and stria terminalis, and higher mean diffusivity in the fornix compared to controls. NODDI modeling revealed that CAH youth have a significantly higher orientation dispersion index in the stria terminalis compared to controls. Decreases in white matter microstructural integrity were associated with smaller hippocampal and amygdala volumes in CAH youth. Conclusions These patterns of microstructure reflect less restricted water diffusion likely due to less coherency in oriented microstructure. These results suggest that white matter microstructural integrity in the fornix and stria terminalis is compromised and may be an additional related brain phenotype alongside affected hippocampus and amygdala neurocircuitry in individuals with CAH.

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P2-333: ASSOCIATION OF WHITE MATTER INTEGRITY AND FUNCTIONAL BRAIN ACTIVITY IN COGNITIVE AGING

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.06.2740 ◽

2019 ◽

Vol 15 ◽

pp. P718-P718

Author(s):

Rebecca J. Melrose ◽

Ariana Stickel ◽

Joseph Veliz ◽

David L. Sultzer ◽

Amy Jimenez

Keyword(s):

White Matter ◽

Cognitive Aging ◽

Brain Activity ◽

White Matter Integrity ◽

Functional Brain ◽

Functional Brain Activity

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Association between APOE e4 and white matter hyperintensity volume, but not total brain volume or white matter integrity

Brain Imaging and Behavior ◽

10.1007/s11682-019-00069-9 ◽

2019 ◽

Vol 14 (5) ◽

pp. 1468-1476 ◽

Cited By ~ 12

Author(s):

Donald M. Lyall ◽

Simon R. Cox ◽

Laura M. Lyall ◽

Carlos Celis-Morales ◽

Breda Cullen ◽

...

Keyword(s):

White Matter ◽

Cognitive Aging ◽

Social Deprivation ◽

Mean Diffusivity ◽

Brain Magnetic Resonance Imaging ◽

Smoking History ◽

White Matter Hyperintensity ◽

Future Research ◽

Uk Biobank ◽

Intermediate Phenotypes

Abstract Apolipoprotein (APOE) e4 genotype is an accepted risk factor for accelerated cognitive aging and dementia, though its neurostructural substrates are unclear. The deleterious effects of this genotype on brain structure may increase in magnitude into older age. This study aimed to investigate in UK Biobank the association between APOE e4 allele presence vs. absence and brain imaging variables that have been associated with worse cognitive abilities; and whether this association varies by cross-sectional age. We used brain magnetic resonance imaging (MRI) and genetic data from a general-population cohort: the UK Biobank (N = 8395 after exclusions). We adjusted for the covariates of age in years, sex, Townsend social deprivation scores, smoking history and cardiometabolic diseases. There was a statistically significant association between APOE e4 genotype and increased (i.e. worse) white matter (WM) hyperintensity volumes (standardised beta = 0.088, 95% confidence intervals = 0.036 to 0.139, P = 0.001), a marker of poorer cerebrovascular health. There were no associations with left or right hippocampal, total grey matter (GM) or WM volumes, or WM tract integrity indexed by fractional anisotropy (FA) and mean diffusivity (MD). There were no statistically significant interactions with age. Future research in UK Biobank utilising intermediate phenotypes and longitudinal imaging hold significant promise for this area, particularly pertaining to APOE e4’s potential link with cerebrovascular contributions to cognitive aging.

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