A potential association of RNF219 ‐ AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

Abstract 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 magnetic resonance imaging (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 blood-oxygen-level-dependent (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.

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P2-412: SEX DIFFERENCES IN WHITE MATTER MICROSTRUCTURE AND ITS EFFECTS ON EXECUTIVE FUNCTION: RESULTS FROM THE BALTIMORE LONGITUDINAL STUDY OF AGING

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.1104 ◽

2006 ◽

Vol 14 (7S_Part_16) ◽

pp. P866-P866

Author(s):

Owen A. Williams ◽

Yang An ◽

Yuankai Huo ◽

Bennett Landman ◽

Susan M. Resnick

Keyword(s):

Sex Differences ◽

Executive Function ◽

Longitudinal Study ◽

White Matter ◽

White Matter Microstructure ◽

Baltimore Longitudinal Study

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White matter microstructure abnormalities and executive function in adolescents with prenatal cocaine exposure

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2013.04.002 ◽

2013 ◽

Vol 213 (2) ◽

pp. 161-168 ◽

Cited By ~ 28

Author(s):

Catherine Lebel ◽

Tamara Warner ◽

John Colby ◽

Lindsay Soderberg ◽

Florence Roussotte ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cocaine Exposure ◽

Prenatal Cocaine Exposure ◽

White Matter Microstructure ◽

Prenatal Cocaine

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Improved Executive Function and Callosal White Matter Microstructure after Rhythm Exercise in Huntington's Disease

Journal of Huntington s Disease ◽

10.3233/jhd-140113 ◽

2014 ◽

Vol 3 (3) ◽

pp. 273-283 ◽

Cited By ~ 19

Author(s):

Claudia Metzler-Baddeley ◽

Jaime Cantera ◽

Elizabeth Coulthard ◽

Anne Rosser ◽

Derek K. Jones ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Huntington's Disease ◽

Huntington’S Disease ◽

White Matter Microstructure

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

10.1101/620443 ◽

2019 ◽

Author(s):

Christina E. Webb ◽

Karen M. Rodrigue ◽

David A. Hoagey ◽

Chris M. Foster ◽

Kristen M. Kennedy

Keyword(s):

Executive Function ◽

White Matter ◽

Structure Function ◽

Association Study ◽

Structural Equation ◽

Equation Modeling ◽

Age Related ◽

White Matter Microstructure ◽

Task Accuracy ◽

Back Task

AbstractThe 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.

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White matter microstructure, cognition, and molecular markers in fragile X premutation females

Neurology ◽

10.1212/wnl.0000000000003979 ◽

2017 ◽

Vol 88 (22) ◽

pp. 2080-2088 ◽

Cited By ~ 17

Author(s):

Annie L. Shelton ◽

Kim M. Cornish ◽

David Godler ◽

Quang Minh Bui ◽

Scott Kolbe ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Corpus Callosum ◽

Fragile X ◽

Mean Diffusivity ◽

White Matter Microstructure ◽

Intron 1 ◽

Exon 1 ◽

Cerebellar Peduncles ◽

Cerebellar Peduncle

Objective:To examine the interrelationships between fragile X mental retardation 1 (FMR1) mRNA and the FMR1 exon 1/intron 1 boundary methylation, white matter microstructure, and executive function, in women with a FMR1 premutation expansion (PM; 55–199 CGG repeats) and controls (CGG < 44).Methods:Twenty women with PM without fragile X-associated tremor/ataxia syndrome (FXTAS) and 20 control women between 22 and 54 years of age completed this study. FMR1 mRNA and methylation levels for 9 CpG sites within the FMR1 exon 1/intron 1 boundary from peripheral blood samples were analyzed. To measure white matter microstructure, diffusion-weighted imaging was used, from which fractional anisotropy (FA) and mean diffusivity (MD) values from anatomic regions within the corpus callosum and cerebellar peduncles were extracted. Executive function was assessed across a range of tasks.Results:No differences were revealed in white matter microstructure between women with PM and controls. However, we reveal that for women with PM (but not controls), higher FMR1 mRNA correlated with lower MD values within the middle cerebellar peduncle and Paced Auditory Serial Addition Test scores, higher methylation of the FMR1 exon 1/intron 1 boundary correlated with lower MD within the inferior and middle cerebellar peduncles and longer prosaccade latencies, and higher FA values within the corpus callosum and cerebellar peduncle regions corresponded to superior executive function.Conclusions:We provide evidence linking white matter microstructure to executive dysfunction and elevated FMR1 mRNA and FMR1 exon 1/intron 1 boundary methylation in women with PM without FXTAS. This suggests that the FXTAS phenotype may not be distinct but may form part of a spectrum of PM involvement.

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Altered white matter microstructure is related to cognition in adults with congenital heart disease

Brain Communications ◽

10.1093/braincomms/fcaa224 ◽

2020 ◽

Author(s):

Melanie Ehrler ◽

Ladina Schlosser ◽

Peter Brugger ◽

Matthias Greutmann ◽

Angela Oxenius ◽

...

Keyword(s):

Quality Of Life ◽

Congenital Heart Disease ◽

Heart Disease ◽

Executive Function ◽

White Matter ◽

Fractional Anisotropy ◽

Congenital Heart ◽

White Matter Microstructure ◽

Executive Function Deficits

Abstract Adults with congenital heart disease are at risk for persisting executive function deficits, which are known to affect academic achievement and quality of life. Alterations in white -matter microstructure are associated with cognitive impairments in adolescents with congenital heart disease. This study aimed to identify microstructural alterations potentially associated with executive function deficits in adults with congenital heart disease. Diffusion tensor imaging and tract-based spatial statistics were conducted in 45 patients (18 females) and 54 healthy controls (26 females) aged 18–32 years. Fractional anisotropy of white matter diffusion was compared between groups and correlated with an executive function score, derived from an extensive neuropsychological test battery. Patients showed widespread bilateral reduction in fractional anisotropy (P < 0.05, multiple comparison corrected) compared to controls. Lower fractional anisotropy was driven by patients with moderate and severe defect complexity (compared to controls: P < 0.001). Executive function scores were lower in patients (P < 0.05) and associated with lower fractional anisotropy in the left superior corona radiata and the corticospinal tract (corrected P < 0.05). Our findings confirm alterations of white matter microstructure in adults with congenital heart disease, mainly in those patients of moderate to severe complexity. These alterations are associated with impairments in executive functioning. A better understanding of the neurocognitive deficits may help counselling and care of patients with congenital heart disease across their lifespan and have the potential to improve their outcome and quality of life.

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